Size-resolved particle measurements of polybrominated diphenyl ethers indoors: Implications for sources and human exposure

Polybrominated diphenyl ethers (PBDEs) are flame retardant polymer additives that are widely detected in outdoor and indoor environments. Release of PBDEs from consumer products leads to high concentrations indoors, but mechanisms of release are poorly understood. While ingestion of dust is a well-studied indoor PBDE exposure route, the importance of inhalation exposure is uncertain. To address these unknowns, dust was collected from household vacuum cleaners, and suspended particulate matter (PM) was collected from the same homes in St. John’s, Canada using a cascade impactor. Size-fractionated PM samples (0.01-18 µm diameter) were analysed for PBDEs. The sum of PBDEs in all PM ranged from 8.7 ± 0.5 to 15.7 ± 0.5 pg/m3, with >50% of PBDE mass in respirable PM (<1 µm). Mass loadings as a function of particle size suggested both abrasion and off-gassing led to the presence of PBDEs in PM. Variability in the PM mass loadings indicated emission mechanisms were both product- and location-dependent. Congener profiles in co-located vacuum dust and PM samples were different, indicating vacuum dust cannot accurately predict PBDE congeners in respirable PM. A calculated lower limit inhalation exposure to PBDEs (0.19 ng/day) is lower than exposure via diet or ingestion of dust, although the different biochemical pathways for inhalation compared to ingestion may have biological effects. This work highlights the importance of contaminant analysis in size-fractionated PM to assess human exposure via inhalation compared to traditional vacuum dust methods

Selective Decontamination of the Reactive Air Pollutant Nitrous Acid via Node-Linker Cooperativity in a Metal-Organic Framework

Nitrous acid (HONO) is a reservoir of NOx and an emerging pollutant having direct impacts on air quality, both in- and outdoors, as well as on human health. In this work, the amine-functionalized metal–organic framework (MOF), UiO-66-NH2, was investigated due to its potential to selectively decontaminate nitrous acid at environmentally relevant concentrations. UiO-66-NH2 proved to be effective in the removal of nitrous acid from a continuous gaseous stream. This is observed via the formation of an aryl diazonium salt that subsequently converts to a phenol with a concomitant release of nitrogen gas. This process is preceded via the formation of the nitrosonium cation (likely protonation from an acidic proton on the node). Thus, UiO-66-NH2 is capable of selectively converting the pollutant nitrous acid to benign products

STAT1-deficient mice spontaneously develop estrogen receptor alpha-positive luminal mammary carcinomas

Abstract Introduction Although breast cancers expressing estrogen receptor-α (ERα) and progesterone receptors (PR) are the most common form of mammary malignancy in humans, it has been difficult to develop a suitable mouse model showing similar steroid hormone responsiveness. STAT transcription factors play critical roles in mammary gland tumorigenesis, but the precise role of STAT1 remains unclear. Herein, we show that a subset of human breast cancers display reduced STAT1 expression and that mice lacking STAT1 surprisingly develop ERα+/PR+ mammary tumors. Methods We used a combination of approaches, including histological examination, gene targeted mice, gene expression analysis, tumor transplantaion, and immunophenotyping, to pursue this study. Results Forty-five percent (37/83) of human ERα+ and 22% (17/78) of ERα- breast cancers display undetectable or low levels of STAT1 expression in neoplastic cells. In contrast, STAT1 expression is elevated in epithelial cells of normal breast tissues adjacent to the malignant lesions, suggesting that STAT1 is selectively downregulated in the tumor cells during tumor progression. Interestingly, the expression levels of STAT1 in the tumor-infiltrating stromal cells remain elevated, indicating that single-cell resolution analysis of STAT1 level in primary breast cancer biopsies is necessary for accurate assessment. Female mice lacking functional STAT1 spontaneously develop mammary adenocarcinomas that comprise &gt; 90% ERα+/PR+ tumor cells, and depend on estrogen for tumor engraftment and progression. Phenotypic marker analyses demonstrate that STAT1-/- mammary tumors arise from luminal epithelial cells, but not myoepithelial cells. In addition, the molecular signature of the STAT1-/- mammary tumors overlaps closely to that of human luminal breast cancers. Finally, introduction of wildtype STAT1, but not a STAT1 mutant lacking the critical Tyr701 residue, into STAT1-/- mammary tumor cells results in apoptosis, demonstrating that the tumor suppressor function of STAT1 is cell-autonomous and requires its transcriptional activity. Conclusions Our findings demonstrate that STAT1 suppresses mammary tumor formation and its expression is frequently lost during breast cancer progression. Spontaneous mammary tumors that develop in STAT1-/- mice closely recapitulate the progression, ovarian hormone responsiveness, and molecular characteristics of human luminal breast cancer, the most common subtype of human breast neoplasms, and thus represent a valuable platform for testing novel treatments and detection modalities

Formation and emission of hydrogen chloride in indoor air

To improve our understanding of chlorine chemistry indoors, reactive chlorine species such as hydrogen chloride (HCl) must be analyzed using fast time-response measurement techniques. Although well studied outdoors, sources of HCl indoors are unknown. In this study, mixing ratios of gaseous HCl were measured at 0.5 Hz in the indoor environment using a cavity ring-down spectroscopy (CRDS) instrument. The CRDS measurement rate provides a major advance in observational capability compared to other established techniques. Measurements of HCl were performed during three types of household activities: (1) floor exposure to bleach, (2) chlorinated and non-chlorinated detergent use in household dishwashers, and (3) cooking events. Surface application of bleach resulted in a reproducible increase of 0.1 ppbv in the affected room. Emissions of HCl from automated dishwashers were observed only when chlorinated detergents were used, with additional HCl emitted during the drying cycle. Increased mixing ratios of HCl were also observed during meal preparation on an electric element stovetop. These observations of HCl derived from household activities indicate either direct emission or secondary production of HCl via chlorine atoms is possible. Calculations of photolysis rate constants of chlorine atom precursors provide evidence that photolysis may contribute to indoor HCl levels

Heating and enriching the intracluster medium

We present numerical simulations of galaxy clusters with stochastic heating from active galactic nuclei (AGN) that are able to reproduce the observed entropy and temperature profiles of non-cool-core (NCC) clusters. Our study uses N-body hydrodynamical simulations to investigate how star formation, metal production, black hole accretion and the associated feedback from supernovae and AGN heat and enrich diffuse gas in galaxy clusters. We assess how different implementations of these processes affect the thermal and chemical properties of the intracluster medium (ICM), using high-quality X-ray observations of local clusters to constrain our models. For the purposes of this study we have resimulated a sample of 25 massive galaxy clusters extracted from the Millennium Simulation. Sub-grid physics is handled using a semi-analytic model of galaxy formation, thus guaranteeing that the source of feedback in our simulations is a population of galaxies with realistic properties. We find that supernova feedback has no effect on the entropy and metallicity structure of the ICM, regardless of the method used to inject energy and metals into the diffuse gas. By including AGN feedback, we are able to explain the observed entropy and metallicity profiles of clusters, as well as the X-ray luminosity-temperature scaling relation for NCC systems. A stochastic model of AGN energy injection motivated by anisotropic jet heating - presented for the first time here - is crucial for this success. With the addition of metal-dependent radiative cooling, our model is also able to produce CC clusters, without overcooling of gas in dense, central regions.Comment: 23 pages, accepted by MNRAS. Some changes in response to referee's comments. New figures 22 & 2

Saturated Fats: A Perspective from Lactation and Milk Composition

For recommendations of specific targets for the absolute amount of saturated fat intake, we need to know what dietary intake is most appropriate? Changing agricultural production and processing to lower the relative quantities of macronutrients requires years to accomplish. Changes can have unintended consequences on diets and the health of subsets of the population. Hence, what are the appropriate absolute amounts of saturated fat in our diets? Is the scientific evidence consistent with an optimal intake of zero? If not, is it also possible that a finite intake of saturated fats is beneficial to overall health, at least to a subset of the population? Conclusive evidence from prospective human trials is not available, hence other sources of information must be considered. One approach is to examine the evolution of lactation, and the composition of milks that developed through millennia of natural selective pressure and natural selection processes. Mammalian milks, including human milk, contain 50% of their total fatty acids as saturated fatty acids. The biochemical formation of a single double bond converting a saturated to a monounsaturated fatty acid is a pathway that exists in all eukaryotic organisms and is active within the mammary gland. In the face of selective pressure, mammary lipid synthesis in all mammals continues to release a significant content of saturated fatty acids into milk. Is it possible that evolution of the mammary gland reveals benefits to saturated fatty acids that current recommendations do not consider

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals