Development of an analytical method to quantify PBDEs, OH-BDEs, HBCDs, 2,4,6-TBP, EH-TBB, and BEH-TEBP in human serum

Polybrominated diphenyl ethers (PBDEs) flame retardants (FRs) were phased-out in the mid-2000s (penta- and octaBDE) and 2013 (decaBDE); however, their hydroxylated metabolites (OH-BDEs) are still commonly detected in human serum. Today, novel FRs such as Firemaster® 550, a mixture that contains two brominated compounds, EH-TBB and BEH-TEBP are used as replacements for PBDEs in some applications, and there is a need to develop a comprehensive analytical method to assess exposure to both legacy PBDEs and novel FRs. This study developed a solid-phase extraction (SPE)-based method to analyze PBDEs, OH-BDEs, 2,4,6-tribromophenol (TBP), hexabromocylcododecane isomers (HBCDs), EH-TBB, and BEH-TEBP in human serum. Briefly, serum proteins were first denatured with formic acid, and then the target analytes were isolated using a SPE column. Finally, the extract was cleaned and fractioned using a silica SPE column. Method performance was assessed by spiking fetal bovine serum with 1–2 ng of the target analytes, and method accuracy was quantified by comparison to a serum Standard Reference Material (SRM). The developed method showed good recovery and accuracy for all target analytes with the exception of the very low and very high molecular weight PBDE congeners. Using this method, 43 serum samples collected from the Healthy Pregnancy, Healthy Baby Study (HPHB) cohort in Durham, NC, USA were analyzed for FRs. A novel finding was the ubiquitous detection of 2,4,6-TBP, at levels greater than the individual PBDE congeners. Furthermore, 2,4,6-TBP was positively correlated with PBDEs, suggesting that they may have a similar source of exposure, or that 2,4,6-TBP may result from metabolism of PBDEs in vivo

Concentrations of polybrominated diphenyl ethers (PBDEs) and 2,4,6-tribromophenol in human placental tissues

Legacy environmental contaminants such as polybrominated diphenyl ethers (PBDEs) are widely detected in human tissues. However, few studies have measured PBDEs in placental tissues, and there are no reported measurements of 2,4,6-tribromophenol (2,4,6-TBP) in placental tissues. Measurements of these contaminants are important for understanding potential fetal exposures, as these compounds have been shown to alter thyroid hormone regulation in vitro and in vivo. In this study, we measured a suite of PBDEs and 2,4,6-TBP in 102 human placental tissues collected between 2010 and 2011 in Durham County, North Carolina, USA. The most abundant PBDE congener detected was BDE-47, with a mean concentration of 5.09 ng/g lipid (range: 0.12–141 ng/g lipid; detection frequency 91%); however, 2,4,6-TBP was ubiquitously detected and present at higher concentrations with a mean concentration of 15.4 ng/g lipid (range:1.31–316 ng/g lipid; detection frequency 100%). BDE-209 was also detected in more than 50% of the samples, and was significantly associated with 2,4,6-TBP in placental tissues, suggesting they may have a similar source, or that 2,4,6-TBP may be a degradation product of BDE-209. Interestingly, BDE-209 and 2,4,6-TBP were negatively associated with age (rs = − 0.16; p = 0.10 and rs = − 0.17; p = 0.08, respectively). The results of this work indicate that PBDEs and 2,4,6-TBP bioaccumulate in human placenta tissue and likely contribute to prenatal exposures to these environmental contaminants. Future studies are needed to determine if these joint exposures are associated with any adverse health measures in infants and children

Predictors of urinary flame retardant concentration among pregnant women

Organophosphate compounds are commonly used in residential furniture, electronics, and baby products as flame retardants and are also used in other consumer products as plasticizers. Although the levels of exposure biomarkers are generally higher among children and decrease with age, relatively little is known about the individual characteristics associated with higher levels of exposure. Here, we investigate urinary metabolites of several organophosphate flame retardants (PFRs) in a cohort of pregnant women to evaluate patterns of exposure

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

G protein-coupled estrogen receptor 1 regulates renal endothelin-1 signaling system in a sex-specific manner

Demographic studies reveal lower prevalence of hypertension among premenopausal females compared to age-matched males. The kidney plays a central role in the maintenance of sodium (Na+) homeostasis and consequently blood pressure. Renal endothelin-1 (ET-1) is a pro-natriuretic peptide that contributes to sex differences in blood pressure regulation and Na+ homeostasis. We recently showed that activation of renal medullary G protein-coupled estrogen receptor 1 (GPER1) promotes ET-1-dependent natriuresis in female, but not male, rats. We hypothesized that GPER1 upregulates the renal ET-1 signaling system in females, but not males. To test our hypothesis, we determined the effect of GPER1 deletion on ET-1 and its downstream effectors in the renal cortex, outer and inner medulla obtained from 12–16-week-old female and male mice. GPER1 knockout (KO) mice and wildtype (WT) littermates were implanted with telemetry transmitters for blood pressure assessment, and we used metabolic cages to determine urinary Na+ excretion. GPER1 deletion did not significantly affect 24-h mean arterial pressure (MAP) nor urinary Na+ excretion. However, GPER1 deletion decreased urinary ET-1 excretion in females but not males. Of note, female WT mice had greater urinary ET-1 excretion than male WT littermates, whereas no sex differences were observed in GPER1 KO mice. GPER1 deletion increased inner medullary ET-1 peptide content in both sexes but increased outer medullary ET-1 content in females only. Cortical ET-1 content increased in response to GPER1 deletion in both sexes. Furthermore, GPER1 deletion notably increased inner medullary ET receptor A (ETA) and decreased outer medullary ET receptor B (ETB) mRNA expression in male, but not female, mice. We conclude that GPER1 is required for greater ET-1 excretion in females. Our data suggest that GPER1 is an upstream regulator of renal medullary ET-1 production and ET receptor expression in a sex-specific manner. Overall, our study identifies the role of GPER1 as a sex-specific upstream regulator of the renal ET-1 system

Novel methodology for predicting the critical salt concentration of bubble coalescence inhibition

Bubble coalescence in some salt solutions can be inhibited if the salt concentration reaches a critical concentration Ccr. There are three models available for Ccr in the literature, but they fail to predict Ccr correctly. The first two models employ the van der Waals attraction power laws to establish Ccr from the discriminant of quadratic or cubic polynomials. To improve the two models, the third model uses the same momentum balance equation of the previous models but different intermolecular force generated by water hydration with exponential decaying. The third prediction for Ccr requires the experimental input for film rupture thickness and is incomplete. We show further in this paper that the third model is incorrect. We propose a novel methodology for determining C cr which resolves the mathematical uncertainties in modeling C cr and can explicitly predict it from any relevant intermolecular forces. The methodology is based on the discovery that Ccr occurs at the local maximum of the balance equation for the capillary pressure, disjoining pressure, and pressure of the Gibbs-Marangoni stress. The novel generic approach is successfully validated using nonlinear equations for complicated disjoining pressure

Establishing a Core Outcome Measure for Graft Health:A Standardized Outcomes in Nephrology-Kidney Transplantation (SONG-Tx) Consensus Workshop Report

Background: Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis but complications and side-effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but it is inconsistently and infrequently measured in trials. We convened a consensus workshop on establishing a core outcome measure for life participation for use in all trials in kidney transplantation. Methods: Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from eight countries participated in six facilitated breakout group discussions. Transcripts were analyzed thematically. Results: Four themes were identified. Returning to normality conveyed the patients’ goals to fulfill their given roles (i.e. in their family, work, and community) and re-establish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of ‘life’ explicitly acknowledged life participation as a subjective concept that could refer to different activities (e.g. employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations post-transplant (e.g. due to complications and side-effects) distinguished between experiences in the first year post-transplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. Conclusions: A feasible and validated core outcome measure for life participation is needed so critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision-making and care of recipients

Automated Force Volume Image Processing for Biological Samples

Atomic force microscopy (AFM) has now become a powerful technique for investigating on a molecular level, surface forces, nanomechanical properties of deformable particles, biomolecular interactions, kinetics, and dynamic processes. This paper specifically focuses on the analysis of AFM force curves collected on biological systems, in particular, bacteria. The goal is to provide fully automated tools to achieve theoretical interpretation of force curves on the basis of adequate, available physical models. In this respect, we propose two algorithms, one for the processing of approach force curves and another for the quantitative analysis of retraction force curves. In the former, electrostatic interactions prior to contact between AFM probe and bacterium are accounted for and mechanical interactions operating after contact are described in terms of Hertz-Hooke formalism. Retraction force curves are analyzed on the basis of the Freely Jointed Chain model. For both algorithms, the quantitative reconstruction of force curves is based on the robust detection of critical points (jumps, changes of slope or changes of curvature) which mark the transitions between the various relevant interactions taking place between the AFM tip and the studied sample during approach and retraction. Once the key regions of separation distance and indentation are detected, the physical parameters describing the relevant interactions operating in these regions are extracted making use of regression procedure for fitting experiments to theory. The flexibility, accuracy and strength of the algorithms are illustrated with the processing of two force-volume images, which collect a large set of approach and retraction curves measured on a single biological surface. For each force-volume image, several maps are generated, representing the spatial distribution of the searched physical parameters as estimated for each pixel of the force-volume image

Metabotropic Glutamate Receptors Protect Oligodendrocytes from Acute Ischemia in the Mouse Optic Nerve.

Studies by Bruce Ransom and colleagues have made a major contribution to show that white matter is susceptible to ischemia/hypoxia. White matter contains axons and the glia that support them, notably myelinating oligodendrocytes, which are highly vulnerable to ischemic-hypoxic damage. Previous studies have shown that metabotropic GluRs (mGluRs) are cytoprotective for oligodendrocyte precursor cells and immature oligodendrocytes, but their potential role in adult white matter was unresolved. Here, we report that group 1 mGluR1/5 and group 2 mGluR3 subunits are expressed in optic nerves from mice aged postnatal day (P)8-12 and P30-35. We demonstrate that activation of group 1 mGluR protects oligodendrocytes against oxygen-glucose deprivation (OGD) in developing and young adult optic nerves. In contrast, group 2 mGluR are shown to be protective for oligodendrocytes against OGD in postnatal but not young adult optic nerves. The cytoprotective effect of group 1 mGluR requires activation of PKC, whilst group 2 mGluR are dependent on negatively regulating adenylyl cyclase and cAMP. Our results identify a role for mGluR in limiting injury of oligodendrocytes in developing and young adult white matter, which may be useful for protecting oligodendrocytes in neuropathologies involving excitoxicity and ischemia/hypoxia

Search for supersymmetry in events with large missing transverse momentum, jets, and at least one tau lepton in 20 fb−1 of √s=8 TeV proton-proton collision data with the ATLAS detector

A search for supersymmetry (SUSY) in events with large missing transverse momentum, jets, at least one hadronically decaying tau lepton and zero or one additional light leptons (electron/muon), has been performed using 20.3fb−1 of proton-proton collision data at √s= 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No excess above the Standard Model background expectation is observed in the various signal regions and 95% confidence level upper limits on the visible cross section for new phenomena are set. The results of the analysis are interpreted in several SUSY scenarios, significantly extending previous limits obtained in the same final states. In the framework of minimal gauge-mediated SUSY breaking models, values of the SUSY breaking scale Λ below 63 TeV are excluded, independently of tan β. Exclusion limits are also derived for an mSUGRA/CMSSM model, in both the R-parity-conserving and R-parity-violating case. A further interpretation is presented in a framework of natural gauge mediation, in which the gluino is assumed to be the only light coloured sparticle and gluino masses below 1090 GeV are excluded