Risk-conscious correction of batch effects: maximising information extraction from high-throughput genomic datasets

Contains additional information and discussion on gPCA (Reese et al., 2013). Table S1. Demonstrates the inverse proportionality between gPCA p-value and the associated ‘delta’ score, reflecting unadjusted relative magnitude of batch effects (Reese et al., 2013). The table shows the scores for all three datasets. Figure S1. Contains an Illustration to further help interpret gPCA p-value vs preserved data variance plots. (DOCX 60 kb

Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibres

<p>Abstract</p> <p>Background</p> <p>It has been suggested that carbon nanotubes might conform to the fibre pathogenicity paradigm that explains the toxicities of asbestos and other fibres on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fibre paradigm but only recently has their biopersistence begun to be investigated. Biopersistence is complex and requires <it>in vivo </it>testing and analysis. However durability, the chemical mimicking of the process of fibre dissolution using <it>in vitro </it>treatment, is closely related to biopersistence and more readily determined. Here, we describe an experimental process to determine the durability of four types of carbon nanotubes in simulated biological fluid (Gambles solution), and their subsequent pathogenicity <it>in vivo </it>using a mouse model sensitive to inflammogenic effects of fibres. The <it>in vitro </it>and <it>in vivo </it>results were compared with well-characterised glass wool and asbestos fibre controls.</p> <p>Results</p> <p>After incubation for up to 24 weeks in Gambles solution, our control fibres were recovered at percentages consistent with their known <it>in vitro </it>durabilities and/or <it>in vivo </it>persistence, and three out of the four types of carbon nanotubes tested (single-walled (CNT_SW) and multi-walled (CNT_TANG2, CNT_SPIN)) showed no, or minimal, loss of mass or change in fibre length or morphology when examined by electron microscopy. However, the fourth type [multi-walled (CNT_LONG1)] lost 30% of its original mass within the first three weeks of incubation, after which there was no further loss. Electron microscopy of CNT_LONG1samples incubated for 10 weeks confirmed that the proportion of long fibres had decreased compared to samples briefly exposed to the Gambles solution. This loss of mass and fibre shortening was accompanied by a loss of pathogenicity when injected into the peritoneal cavities of C57Bl/6 mice compared to fibres incubated briefly. CNT_SWdid not elicit an inflammogenic effect in the peritoneal cavity assay used here.</p> <p>Conclusions</p> <p>These results support the view that carbon nanotubes are generally durable but may be subject to bio-modification in a sample-specific manner. They also suggest that pristine carbon nanotubes, either individually or in rope-like aggregates of sufficient length and aspect ratio, can induce asbestos-like responses in mice, but that the effect may be mitigated for certain types that are less durable in biological systems. Results indicate that durable carbon nanotubes that are either short or form tightly bundled aggregates with no isolated long fibres are less inflammogenic in fibre-specific assays.</p

Seeing and Overcoming the Complexities of Intersectionality

Background: Intersectionality contests that individuals have multiple characteristics in their identity that cannot be siloed or deemed exclusive to each other. Understanding and utilising an intersectional lens in organisations can increase inclusion of individuals and organisational performance. An educational package known as the IntersectionalityWalk (IW) was developed by the authors, piloted, and evaluated in order to break down the commonly held descriptors of diversity silos that fragments inclusion, and to understand how various identity characteristics compound disadvantage. The paper outlines the need to transition from siloed views of diversity to a more intrinsic view of identity to achieve inclusivity. Methods: The IW was developed and trialled with a series of work-based scenarios and realistic multifaceted personas. Data collection occurred preand post-IW utilising a mixed methods approach. Responses to Likert scale surveys and open-ended questions were captured and analysed via inductive and grounded theory perspectives. Results: An improved awareness and understanding of individual knowledge, reflectivity and positionality relating to intersectionality and intersectional approaches was reported on completion of the IW. Furthermore, responses reported how and why organisations can approach and improve inclusivity via using intersectional approaches. Conclusions: The IW as an educational package has a positive impact and is a key linkage for all employers to build an inclusive culture and to harness the talent of all employees. Further research will occur to measure the implemented change in organisations following the IW

Release of engineered nanomaterials from personal care products throughout their life cycle

The impetus for this study was to provide release estimates that can serve to improve predictions of engineered nanomaterial (ENM) exposure for risk assessment. We determined the likely release of ENMs from personal care products (PCPs) through a consumer survey on use and disposal habits, and research on the types and quantities of ENMs in PCPs. Our estimates show that in the US zinc oxide (ZnO), with 1,800-2,100 mt yr-1, and titanium dioxide (TiO2), with 870-1,000 mt yr-1, represent 94 % of ENMs released into the environment or landfills from the use of PCPs. Around 36-43 % of ENMs from PCPs were estimated to end up in landfills, 24-36 % released to soils, 0.7-0.8 % to air, and 28-32 % to water bodies. ENMs in sunscreen represent around 81-82 % of total release, from ZnO and TiO2 as UV blockers, followed by facial moisturizer (7.5 %), foundation (5.7 %), and hair coloring products (3.1 %). Daily care products such as body wash, shampoo, and conditioner had by far the highest per capita and total use, but contributed little to the ENM release estimates as these products generally contain little or no ENMs. However, if ENMs are incorporated into these daily care products, this may substantially increase ENM release. © 2014 Springer Science+Business Media

Surface coatings of ZnO nanoparticles mitigate differentially a host of transcriptional, protein and signalling responses in primary human olfactory cells

Background: Inhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats. In close proximity to the olfactory bulb is the olfactory mucosa, within which resides a niche of multipotent cells. Cells isolated from this area may provide a relevant in vitro system to investigate potential effects of workplace exposure to inhaled zinc oxide nanoparticles. Methods: Four types of commercially-available zinc oxide (ZnO) nanoparticles, two coated and two uncoated, were examined for their effects on primary human cells cultured from the olfactory mucosa. Human olfactory neurosphere-derived (hONS) cells from healthy adult donors were analyzed for modulation of cytokine levels, activation of intracellular signalling pathways, changes in gene-expression patterns across the whole genome, and compromised cellular function over a 24 h period following exposure to the nanoparticles suspended in cell culture medium. Results: ZnO nanoparticle toxicity in hONS cells was mediated through a battery of mechanisms largely related to cell stress, inflammatory response and apoptosis, but not activation of mechanisms that repair damaged DNA. Surface coatings on the ZnO nanoparticles mitigated these cellular responses to varying degrees. Conclusions: The results indicate that care should be taken in the workplace to minimize generation of, and exposure to, aerosols of uncoated ZnO nanoparticles, given the adverse responses reported here using multipotent cells derived from the olfactory mucosa

LipiD-QuanT : a novel method to quantify lipid accumulation in live cells

Lipid droplets (LDs) are the main storage organelles for triglycerides. Elucidation of lipid accumulation mechanisms and metabolism are essential to understand obesity and associated diseases. Adipogenesis has been well studied in murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell lines. However, most techniques for measuring LD accumulation are either not quantitative or can be destructive to samples. Here, we describe a novel, label-free LD quantification technique (LipiD-QuanT) to monitor lipid dynamics based on automated image analysis of phase contrast microscopy images acquired during in vitro human adipogenesis. We have applied LipiD-QuanT to measure LD accumulation during differentiation of SGBS cells. We demonstrate that LipiD-QuanT is a robust, nondestructive, time- and cost-effective method compared with other triglyceride accumulation assays based on enzymatic digest or lipophilic staining. Further, we applied LipiD-QuanT to measure the effect of four potential pro- or antiobesogenic substances: DHA, rosiglitazone, elevated levels of D-glucose, and zinc oxide nanoparticles. Our results revealed that 2 µmol/l rosiglitazone treatment during adipogenesis reduced lipid production and caused a negative shift in LD diameter size distribution, but the other treatments showed no effect under the conditions used here.11 page(s