•A narrative review is presented of the potential toxicity of plastic particles to humans.•Nanoparticles are more readily absorbed than microparticles.•Atmospheric pollution and ingestion of ...shellfish are major sources of plastic particles.•Toxicity is unlikely unless absorption of plastic particles is high and continuous.
Macro-plastic pollution is found in terrestrial and marine environments and is degraded to micro-particles (MP) and nano-particles (NP) of plastic. These can enter the human food chain either by inhalation or by ingestion, particularly of shellfish and crustaceans. Absorption across the gastrointestinal tract is relatively low, especially for MPs, which appear to have little toxicity. However, NPs are more readily absorbed and may accumulate in the brain, liver and other tissues in aquatic species and other animals. Studies using nanoparticles of other materials suggest that toxicity could potentially affect the central nervous system and the reproductive system, although this would be unlikely unless exposure levels were very high and absorption was increased by physiological factors.
Emerging evidence suggests that prenatal exposures may affect long-term health outcomes. In utero exposure to smoking is associated with an increased risk of overweight and obesity in children and ...adolescents. However, few studies have examined how prenatal exposure to parental smoking influences the risk of obesity during adulthood and whether these associations are independent of childhood and adolescent adiposity. The aim of the current study was to investigate whether prenatal exposure to parental smoking influences body size during adulthood and whether any association may be mediated by childhood and adolescent body size.
We investigated the association between parental smoking during pregnancy and the risk of being overweight and obese during adulthood and at age 18 and adiposity during childhood among 35 370 participants in the Nurses' Health Study II. Data on smoking during pregnancy and socioeconomic variables were provided by the mothers, and anthropometric data and adult risk factors were reported by participants.
After adjustment for socioeconomic and behavioral variables, maternal smoking during pregnancy was associated with adiposity at ages 5-10, 18 and during adulthood. For age 18 overweight, the odd ratios, ORs (95% confidence intervals, CIs) for 1-14, 15-24 and 25+cigarettes per day were 1.13 (1.18-1.50), 1.40 (1.20-1.64) and 1.15 (0.79-1.69), and for obesity were 1.41 (1.14-1.75), 1.69 (1.31-2.18) and 2.36 (1.44-3.86). The corresponding ORs (95% CIs) for obesity during adulthood were 1.26 (1.16-1.37), 1.46 (1.30-1.63) and 1.43 (1.10-1.86). Risk of adiposity was not increased among daughters whose mothers stopped smoking during the first trimester (OR (95% CI) for overweight (1.03 (95% CI 0.90-1.17)) and for obesity (1.12 (95% CI 0.97-1.30)). Women whose fathers smoked during pregnancy were also at an increased risk of being overweight and obese during adulthood with covariate-adjusted ORs (95% CIs) for obesity of 1.19 (1.11-1.29) for 1-14 cigarettes per day, 1.27 (1.18-1.37) for 15-24 cigarettes per day and 1.40 (1.27-1.54) for 25+ cigarettes per day compared with fathers who did not smoke (Ptrend<0.0001). Paternal smoking during pregnancy was also associated with an increased risk of obesity at age 18 among those whose fathers smoked 15 or more cigarettes per day but was not associated with childhood body size.
Maternal smoking during pregnancy was associated in a dose-response manner with overweight and obesity in the daughter across adolescence and adult life. Smoking cessation during the first trimester appears to mitigate this excess risk.Paternal smoking was also associated with the risk of being overweight and obese of the adult daughter and this association persisted after adjustment for maternal smoking.
Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, ...such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities.
We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches.
We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer.
Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If these relationships are confirmed, these findings may have important implications in screening practices and in the management and care of endometriosis patients.
We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass <30 ...GeV/c(2), with the signal region blinded. Eleven events were observed after unblinding. We set an upper limit on the spin-independent WIMP-nucleon cross section of 1.2×10(-42) cm(2) at 8 GeV/c(2). This result is in tension with WIMP interpretations of recent experiments and probes new parameter space for WIMP-nucleon scattering for WIMP masses <6 GeV/c(2).
Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct ...a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10
) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
DNA barcoding has become a well‐funded, global enterprise since its proposition as a technique for species identification, delimitation and discovery in 2003. However, the rapid development of next ...generation sequencing (NGS) has the potential to render DNA barcoding irrelevant because of the speed with which it generates large volumes of genomic data. To avoid obsolescence, the DNA barcoding movement must adapt to use this new technology. This review examines the DNA barcoding enterprise, its continued resistance to improvement and the implications of this on the future of the discipline. We present the consistent failure of DNA barcoding to recognize its limitations and evolve its methodologies, reducing the usefulness of the data produced by the movement and throwing into doubt its ability to embrace NGS.
The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting ...massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c^{2}.
Activating transcription factor 4 (ATF4) is a transcription factor induced under severe hypoxia and a component of the PERK pathway involved in the unfolded protein response (UPR), a process that ...protects cells from the negative consequences of endoplasmic reticulum (ER) stress. In this study, we have used small interfering RNA (siRNA) and microarray analysis to provide the first whole-genome analysis of genes regulated by ATF4 in cancer cells in response to severe and prolonged hypoxic stress. We show that ATF4 is required for ER stress and hypoxia-induced expansion of autophagy. MAP1LC3B (LC3B) is a key component of the autophagosomal membrane, and in this study we demonstrate that ATF4 facilitates autophagy through direct binding to a cyclic AMP response element binding site in the LC3B promoter, resulting in LC3B upregulation. Previously, we have shown that Bortezomib-induced ATF4 stabilization, which then upregulated LC3B expression and had a critical role in activating autophagy, protecting cells from Bortezomib-induced cell death. We also showed that severe hypoxia stabilizes ATF4. In this study, we demonstrate that severe hypoxia leads to ER stress and induces ATF4-dependent autophagy through LC3 as a survival mechanism. In summary, we show that ATF4 has a key role in the regulation of autophagy in response to ER stress and provide a direct mechanistic link between the UPR and the autophagic machinery.
We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σE = 3.86 ± 0.04 ( stat ) +0.19 −0.00 ( syst ) ...eV . This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV / c2 , with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.
SuperCDMS SNOLAB will be a next-generation experiment aimed at directly detecting low-mass particles (with masses ≤10 GeV/c2) that may constitute dark matter by using cryogenic detectors of two types ...(HV and iZIP) and two target materials (germanium and silicon). The experiment is being designed with an initial sensitivity to nuclear recoil cross sections ∼1×10−43 cm2 for a dark matter particle mass of 1 GeV/c2, and with capacity to continue exploration to both smaller masses and better sensitivities. The phonon sensitivity of the HV detectors will be sufficient to detect nuclear recoils from sub-GeV dark matter. A detailed calibration of the detector response to low-energy recoils will be needed to optimize running conditions of the HV detectors and to interpret their data for dark matter searches. Low-activity shielding, and the depth of SNOLAB, will reduce most backgrounds, but cosmogenically produced H3 and naturally occurring Si32 will be present in the detectors at some level. Even if these backgrounds are 10 times higher than expected, the science reach of the HV detectors would be over 3 orders of magnitude beyond current results for a dark matter mass of 1 GeV/c2. The iZIP detectors are relatively insensitive to variations in detector response and backgrounds, and will provide better sensitivity for dark matter particles with masses ≳5 GeV/c2. The mix of detector types (HV and iZIP), and targets (germanium and silicon), planned for the experiment, as well as flexibility in how the detectors are operated, will allow us to maximize the low-mass reach, and understand the backgrounds that the experiment will encounter. Upgrades to the experiment, perhaps with a variety of ultra-low-background cryogenic detectors, will extend dark matter sensitivity down to the “neutrino floor,” where coherent scatters of solar neutrinos become a limiting background.