Metal oxide nanoparticles are commonly used in personal-care formulations as protective agents against exposure to ultraviolet radiation. Although previous research has concluded that nanoparticles do not penetrate healthy skin, it remains contentious whether this conclusion holds under normal conditions of sunscreen use. Humans (n = 20) were exposed to sunscreens containing zinc oxide (ZnO) particles to determine if Zn from the particles was absorbed through skin over five consecutive days under outdoor conditions. Two sunscreens were tested-"nano sunscreen" containing 19-nm nanoparticles and "bulk sunscreen" containing > 100-nm particles. Venous blood and urine samples were collected 8 days before exposure, twice daily during the trial, and 6 days post-exposure. As the first application in nanotechnology studies, stable isotope tracing was used where the ZnO, enriched to > 99% with the stable isotope (68)Zn, allowed dermally absorbed zinc to be distinguished from naturally occurring zinc. The overwhelming majority of applied (68)Zn was not absorbed, although blood and urine samples from all subjects exhibited small increases in levels of tracer (68)Zn. The amount of tracer detected in blood after the 5-day application period was ∼1/1000 th that of total Zn in the blood compartment. Tracer levels in blood continued to increase beyond the 5-day application phase in contrast to those in urine. Levels of (68)Zn in blood and urine from females receiving the nano sunscreen appeared to be higher than males receiving the same treatment and higher than all subjects receiving the bulk sunscreen. It is not known whether (68)Zn has been absorbed as ZnO particles or soluble Zn or both.

BackgroundBatch effects are a persistent and pervasive form of measurement noise which undermine the scientific utility of high-throughput genomic datasets. At their most benign, they reduce the power of statistical tests resulting in actual effects going unidentified. At their worst, they constitute confounds and render datasets useless. Attempting to remove batch effects will result in some of the biologically meaningful component of the measurement (i.e. signal) being lost. We present and benchmark a novel technique, called Harman. Harman maximises the removal of batch noise with the constraint that the risk of also losing biologically meaningful component of the measurement is kept to a fraction which is set by the user.ResultsAnalyses of three independent publically available datasets reveal that Harman removes more batch noise and preserves more signal at the same time, than the current leading technique. Results also show that Harman is able to identify and remove batch effects no matter what their relative size compared to other sources of variation in the dataset. Of particular advantage for meta-analyses and data integration is Harman’s superior consistency in achieving comparable noise suppression - signal preservation trade-offs across multiple datasets, with differing number of treatments, replicates and processing batches.ConclusionHarman’s ability to better remove batch noise, and better preserve biologically meaningful signal simultaneously within a single study, and maintain the user-set trade-off between batch noise rejection and signal preservation across different studies makes it an effective alternative method to deal with batch effects in high-throughput genomic datasets. Harman is flexible in terms of the data types it can process. It is available publically as an R package (https://bioconductor.org/packages/release/bioc/html/Harman.html), as well as a compiled Matlab package (http://www.bioinformatics.csiro.au/harman/) which does not require a Matlab license to run.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1212-5) contains supplementary material, which is available to authorized users.

BackgroundEvidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials.This study utilized a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/day) or placebo supplements from 20 weeks’ gestation to delivery. Blood spots were collected from the children at birth (n = 991) and blood leukocytes at 5 years (n = 667). Global DNA methylation was measured in all samples, and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years.ResultsThere were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect.ConclusionMaternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans and point the way for future studies.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12605000569606 and ACTRN12611001127998 Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0281-7) contains supplementary material, which is available to authorized users.

Previous studies have shown no, or very limited, skin penetration of metal oxide nanoparticles following topical application of sunscreens, yet concerns remain about their safety compared to larger particles. Here, we assessed the comparative dermal absorption of a traceable form of Zn (68Zn) from 68ZnO nano-sized and larger particles in sunscreens. Sunscreens were applied to the backs of virgin or pregnant hairless mice over four days. Control groups received topical applications of the sunscreen formulation containing no ZnO particles, or no treatment. Major organs were assessed for changes in 68Zn/64Zn ratios, 68Zn tracer and total Zn concentrations. Short-term biological impact was assessed by measuring levels of serum amyloid A in blood, and by performing whole-genome transcriptional profiling on livers from each group. Increased concentrations of 68Zn tracer were detected in internal organs of mice receiving topical applications of 68ZnO (nano-sized and larger particles), as well as in fetal livers from treated dams, compared with controls. Furthermore, concentrations of 68Zn in organs of virgin mice treated with sunscreen containing 68ZnO nanoparticles were found to be significantly higher than in mice treated with sunscreen containing larger 68ZnO particles. However, no ZnO-mediated change in total Zn concentration in any of the major organs was observed. Thus, despite 68Zn absorption, which may have been in the form of soluble 68Zn species or 68ZnO particles (not known), Zn homeostasis was largely maintained, and the presence of ZnO particles in sunscreen did not elicit an adverse biological response in the mice following short-term topical applications.