Chronic toxicity of an environmentally relevant and equitoxic ratio of five metals to two Antarctic marine microalgae shows complex mixture interactivity

© 2018 Metal contaminants are rarely present in the environment individually, yet environmental quality guidelines are derived from single-metal toxicity data. Few metal mixture studies have investigated more than binary mixtures and many are at unrealistically high effect concentrations to freshwater organisms. This study investigates the toxicity of five metals (Cd, Cu, Ni, Pb, and Zn) to the Antarctic marine microalgae Phaeocystis antarctica and Cryothecomonas armigera. Two mixtures were tested: (i) an equitoxic mixture of contaminants present at their single-metal EC10 concentrations, and (ii) an environmental mixture based on the ratio metal concentrations in a contaminated Antarctic marine bay. Observed toxicity, as chronic population growth rate inhibition, was compared to Independent Action (IA) and Concentration Addition (CA) predictions parameterised to use EC10 values. This allowed for the inclusion of metals with low toxicities. The biomarkers chlorophyll a fluorescence, cell size and complexity, and intracellular lipid concentrations were assessed to investigate possible mechanisms behind metal-mixture interactions. Both microalgae had similar responses to the equitoxic mixture: non-interactive by IA and antagonistic by CA. Toxicity from the environmental mixture was antagonistic by IA to P. antarctica; however, to C. armigera it was concentration-dependent with antagonism at low toxicities and synergism at high toxicities by both IA and CA. Differences in dissolved organic carbon production and detoxification mechanisms may be responsible for these responses and warrants further investigation. This study shows that mixture toxicity interactions can be ratio, species, and concentration dependent. The responses of the microalgae to different mixture ratios highlight the need to assess toxicity at environmentally realistic metal ratios. Parameterising IA and CA reference models to use EC10s allowed for the inclusion of metals at low effect concentrations, which may otherwise be ignored. Reference mixture models are generally suitable for predicting chronic toxicity of metals to these marine microalgae at environmentally realistic ratios and concentrations. Toxic metal-mixture interactions were found to be concentration, ratio, and species dependent in exposures to two Antarctic marine microalgae

Assessing the Risk of Metals and Their Mixtures in the Antarctic Nearshore Marine Environment with Diffusive Gradients in Thin-Films

© 2019 American Chemical Society. Robust environmental assessments and contaminant monitoring in Antarctic near-shore marine environments need new techniques to overcome challenges presented by a highly dynamic environment. This study outlines an approach for contaminant monitoring and risk assessment in Antarctic marine conditions using diffusive gradients in thin-films (DGT) coupled to regionally specific ecotoxicology data and environmental quality standards. This is demonstrated in a field study where DGT samplers were deployed in the near-shore marine environment of East Antarctica around the operational Casey station and the abandoned Wilkes station to measure the time-averaged biologically available fraction of metal contaminants. The incorporation of DGT-labile concentrations to reference toxicity mixture models for three Antarctic organisms predicted low toxic effects (<5% effect to the growth or development of each organism). The comparison of metal concentrations to the Australian and New Zealand default water quality guideline values (WQGVs) showed no marine site exceeding the WQGVs for 95% species protection. However, all sites exceeded the 99% WQGVs due to copper concentrations that are likely of geogenic origin (i.e., not from anthropogenic sources). This study provides evidence supporting the use of the DGT technique to monitor contaminants and assess their environmental risk in the near-shore marine environment of Antarctica

Phase Structure and Compactness

In order to study the influence of compactness on low-energy properties, we compare the phase structures of the compact and non-compact two-dimensional multi-frequency sine-Gordon models. It is shown that the high-energy scaling of the compact and non-compact models coincides, but their low-energy behaviors differ. The critical frequency $\beta^2 = 8\pi$ at which the sine-Gordon model undergoes a topological phase transition is found to be unaffected by the compactness of the field since it is determined by high-energy scaling laws. However, the compact two-frequency sine-Gordon model has first and second order phase transitions determined by the low-energy scaling: we show that these are absent in the non-compact model.Comment: 21 pages, 5 figures, minor changes, final version, accepted for publication in JHE

The Competition of Charge Remote and Charge Directed Fragmentation Mechanisms in Quaternary Ammonium Salt Derivatized Peptides—An Isotopic Exchange Study

Derivatization of peptides as quaternary ammonium salts (QAS) is a promising method for sensitive detection by electrospray ionization tandem mass spectrometry (Cydzik et al. J. Pept. Sci.2011, 17, 445–453). The peptides derivatized by QAS at their N-termini undergo fragmentation according to the two competing mechanisms – charge remote (ChR) and charge directed (ChD). The absence of mobile proton in the quaternary salt ion results in ChR dissociation of a peptide bond. However, Hofmann elimination of quaternary salt creates an ion with one mobile proton leading to the ChD fragmentation. The experiments on the quaternary ammonium salts with deuterated N-alkyl groups or amide NH bonds revealed that QAS derivatized peptides dissociate according to the mixed ChR-ChD mechanism. The isotopic labeling allows differentiation of fragments formed according to ChR and ChD mechanisms

Feasibility of identifying families for genetic studies of birth defects using the National Health Interview Survey

BACKGROUND: The purpose of this study was to determine whether the National Health Interview Survey is a useful source to identify informative families for genetic studies of birth defects. METHODS: The 1994/1995 National Health Interview Survey (NHIS) was used to identify households where individuals with two or more birth defects reside. Four groups of households were identified: 1) single non-familial (one individual with one birth defect); 2) single familial (more than one individual with one birth defect); 3) multiple non-familial (one individual with more than one birth defect), and 4) multiple familial (more than one individual with more than one birth defect). The March 2000 U.S. Census on households was used to estimate the total number of households in which there are individuals with birth defects. RESULTS: Of a total of 28,094 households and surveyed about birth defects and impairments, 1,083 single non-familial, 55 multiple non-familial, 54 single familial, and 8 multiple familial households were identified. Based on the 2000 U.S. census, it is estimated that there are 4,472,385 households where at least one person has one birth defect in the United States and in 234,846 of them there are at least two affected individuals. Western states had the highest prevalence rates. CONCLUSIONS: Population-based methods, such as the NHIS, are modestly useful to identify the number and the regions where candidate families for genetic studies of birth defects reside. Clinic based studies and birth defects surveillance systems that collect family history offer better probability of ascertainment

Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

BACKGROUND: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. METHODS: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with metastatic breast (n=75) and lung (n=71) cancer. Molecular markers including Human Epidermal growth factor Receptor 2 (HER2) were evaluated on CTCs by fluorescence in situ hybridisation (FISH) and compared to patients' primary and metastatic cancer. RESULTS: The median cell count from patients with breast cancer using the CPK was 117 vs 4 for CEK (P<0.0001). Lung cancer samples were similar; CPK: 145 cells vs CEK:4 cells (P<0.0001). Recovered CTCs were relatively pure (60-70%) and were evaluable by FISH and immunofluorescence. A total of 10 of 30 (33%) breast cancer patients with HER2-negative primary and metastatic tissue had HER2-amplified CTCs. CONCLUSION: The CPK method provides a high yield of relatively pure CTCs, facilitating their molecular characterisation. Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour

Is it harder to know or to reason? Analyzing two-tier science assessment items using the Rasch measurement model

Two-tier multiple-choice (TTMC) items are used to assess students’ knowledge of a scientific concept for tier 1 and their reasoning about this concept for tier 2. But are the knowledge and reasoning involved in these tiers really distinguishable? Are the tiers equally challenging for students? The answers to these questions influence how we use and interpret TTMC instruments. We apply the Rasch measurement model on TTMC items to see if the items are distinguishable according to different traits (represented by the tier), or according to different content sub-topics within the instrument, or to both content and tier. Two TTMC data sets are analyzed: data from Singapore and Korea on the Light Propagation Diagnostic Instrument (LPDI), data from the United States on the Classroom Test of Scientific Reasoning (CTSR). Findings for LPDI show that tier-2 reasoning items are more difficult than tier-1 knowledge items, across content sub-topics. Findings for CTSR do not show a consistent pattern by tier or by content sub-topic. We conclude that TTMC items cannot be assumed to have a consistent pattern of difficulty by tier—and that assessment developers and users need to consider how the tiers operate when administering TTMC items and interpreting results. Researchers must check the tiers’ difficulties empirically during validation and use. Though findings from data in Asian contexts were more consistent, further study is needed to rule out differences between the LPDI and CTSR instruments

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes