The structure of volcanic cristobalite in relation to its toxicity; relevance for the variable crystalline silica hazard

BACKGROUND: Respirable crystalline silica (RCS) continues to pose a risk to human health worldwide. Its variable toxicity depends on inherent characteristics and external factors which influence surface chemistry. Significant population exposure to RCS occurs during volcanic eruptions, where ashfall may cover hundreds of square km and exposure may last years. Occupational exposure also occurs through mining of volcanic deposits. The primary source of RCS from volcanoes is through collapse and fragmentation of lava domes within which cristobalite is mass produced. After 30 years of research, it is still not clear if volcanic ash is a chronic respiratory health hazard. Toxicological assays have shown that cristobalite-rich ash is less toxic than expected. We investigate the reasons for this by determining the physicochemical/structural characteristics which may modify the pathogenicity of volcanic RCS. Four theories are considered: 1) the reactivity of particle surfaces is reduced due to co-substitutions of Al and Na for Si in the cristobalite structure; 2) particles consist of aggregates of cristobalite and other phases, restricting the surface area of cristobalite available for reactions in the lung; 3) the cristobalite surface is occluded by an annealed rim; 4) dissolution of other volcanic particles affects the surfaces of RCS in the lung. METHODS: The composition of volcanic cristobalite crystals was quantified by electron microprobe and differences in composition assessed by Welch's two sample t-test. Sections of dome-rock and ash particles were imaged by scanning and transmission electron microscopy, and elemental compositions of rims determined by energy dispersive X-ray spectroscopy. RESULTS: Volcanic cristobalite contains up to 4 wt. % combined Al(2)O(3) and Na(2)O. Most cristobalite-bearing ash particles contain adhered materials such as feldspar and glass. No annealed rims were observed. CONCLUSIONS: The composition of volcanic cristobalite particles gives insight into previously-unconsidered inherent characteristics of silica mineralogy which may affect toxicity. The structural features identified may also influence the hazard of other environmentally and occupationally produced silica dusts. Current exposure regulations do not take into account the characteristics that might render the silica surface less harmful. Further research would facilitate refinement of the existing simple, mass-based silica standard by taking into account composition, allowing higher standards to be set in industries where the silica surface is modified.Natural Environment Research Council (NERC)Moyes Foundation - studentshi

Instrumental variable analysis using offspring BMI in childhood as an indicator of parental BMI in relation to mortality

Abstract Childhood BMI shows associations with adult mortality, but these may be influenced by effects of ill health in childhood on BMI and later mortality. To avoid this, we used offspring childhood BMI as an instrumental variable (IV) for own BMI in relation to mortality and compared it with conventional associations of own childhood BMI and own mortality. We included 36,097 parent–offspring pairs with measured heights and weights from the Copenhagen School Health Records Register and register-based information on death. Hazard ratios (HR) were estimated using adjusted Cox regression models. For all-cause mortality, per zBMI at age 7 the conventional HR = 1.07 (95%CI: 1.04–1.09) in women and 1.02 (95%CI: 0.92–1.14) in men, whereas the IV HR = 1.23 (95%CI: 1.15–1.32) in women and 1.05 (95%CI: 0.94–1.17) in men. Per zBMI at age 13, the conventional HR = 1.11 (95%CI: 1.08–1.15) in women and 1.03 (95%CI: 0.99–1.06) in men, whereas the IV HR = 1.30 (95%CI: 1.19–1.42) in women and 1.15 (95%CI: 1.04–1.29) in men. Only conventional models showed indications of J-shaped associations. Our IV analyses suggest that there is a causal relationship between BMI and mortality that is positive at both high and low BMI values

Mapping a candidate gene (MdMYB10) for red flesh and foliage colour in apple

<p>Abstract</p> <p>Background</p> <p>Integrating plant genomics and classical breeding is a challenge for both plant breeders and molecular biologists. Marker-assisted selection (MAS) is a tool that can be used to accelerate the development of novel apple varieties such as cultivars that have fruit with anthocyanin through to the core. In addition, determining the inheritance of novel alleles, such as the one responsible for red flesh, adds to our understanding of allelic variation. Our goal was to map candidate anthocyanin biosynthetic and regulatory genes in a population segregating for the red flesh phenotypes.</p> <p>Results</p> <p>We have identified the <it>Rni </it>locus, a major genetic determinant of the red foliage and red colour in the core of apple fruit. In a population segregating for the red flesh and foliage phenotype we have determined the inheritance of the <it>Rni </it>locus and DNA polymorphisms of candidate anthocyanin biosynthetic and regulatory genes. Simple Sequence Repeats (SSRs) and Single Nucleotide Polymorphisms (SNPs) in the candidate genes were also located on an apple genetic map. We have shown that the MdMYB10 gene co-segregates with the <it>Rni </it>locus and is on Linkage Group (LG) 09 of the apple genome.</p> <p>Conclusion</p> <p>We have performed candidate gene mapping in a fruit tree crop and have provided genetic evidence that red colouration in the fruit core as well as red foliage are both controlled by a single locus named <it>Rni</it>. We have shown that the transcription factor MdMYB10 may be the gene underlying <it>Rni </it>as there were no recombinants between the marker for this gene and the red phenotype in a population of 516 individuals. Associating markers derived from candidate genes with a desirable phenotypic trait has demonstrated the application of genomic tools in a breeding programme of a horticultural crop species.</p

Seniority-based entitlements : extent, policy debates and research

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Oscar MolinaSeniority systems - schemes that allot improving employment rights or benefits to employees as their length of employment increases - have not been widely studied. This report provides the first comprehensive study comparing the design and spread of seniority-based entitlements (SBEs) in Europe and mapping related policy debates. It is primarily based on contributions from the Network of Eurofound Correspondents, covering the 28 EU Member States and Norway, but also presents aggregate seniority-earnings curves for the EU based on data from the Structure of Earnings Survey. The aim of the report is to take stock of the currently existing different types of SBEs in the private and public sectors. It concludes that despite an obvious trend to remove them from regulations or reform them, a substantial amount of such entitlements is here to stay. Paradoxically, countries which have regulations on seniority pay in place tend to have flatter aggregate seniority-earnings curves than countries without such regulations

Brief Communication External globus pallidus stimulation modulates brain connectivity in Huntington&apos;s disease

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington&apos;s disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model

Tandem fusion of hepatitis B core antigen allows assembly of virus-like particles in bacteria and plants with enhanced capacity to accommodate foreign proteins

The core protein of the hepatitis B virus, HBcAg, assembles into highly immunogenic viruslike particles (HBc VLPs) when expressed in a variety of heterologous systems. Specifically, the major insertion region (MIR) on the HBcAg protein allows the insertion of foreign sequences, which are then exposed on the tips of surface spike structures on the outside of the assembled particle. Here, we present a novel strategy which aids the display of whole proteins on the surface of HBc particles. This strategy, named tandem core, is based on the production of the HBcAg dimer as a single polypeptide chain by tandem fusion of two HBcAg open reading frames. This allows the insertion of large heterologous sequences in only one of the two MIRs in each spike, without compromising VLP formation. We present the use of tandem core technology in both plant and bacterial expression systems. The results show that tandem core particles can be produced with unmodified MIRs, or with one MIR in each tandem dimer modified to contain the entire sequence of GFP or of a camelid nanobody. Both inserted proteins are correctly folded and the nanobody fused to the surface of the tandem core particle (which we name tandibody) retains the ability to bind to its cognate antigen. This technology paves the way for the display of natively folded proteins on the surface of HBc particles either through direct fusion or through non-covalent attachment via a nanobody

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H