Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in Fundulus heteroclitus

Widespread contamination of aquatic systems with polycyclic aromatic hydrocarbons (PAHs) has led to concern about effects of PAHs on aquatic life. Some PAHs have been shown to cause deformities in early life stages of fish that resemble those elicited by planar halogenated aromatic hydrocarbons (pHAHs) that are agonists for the aryl hydrocarbon receptor (AHR). Previous studies have suggested that activity of cytochrome P4501A, a member of the AHR gene battery, is important to the toxicity of pHAHs, and inhibition of CYP1A can reduce the early-life-stage toxicity of pHAHs. In light of the effects of CYP1A inhibition on pHAH-derived toxicity, we explored the impact of both model and environmentally relevant CYP1A inhibitors on PAH-derived embryotoxicity. We exposed Fundulus heteroclitus embryos to two PAH-type AHR agonists, β-naphthoflavone and benzo(a)pyrene, and one pHAH-type AHR agonist, 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), alone and in combination with several CYP1A inhibitors. In agreement with previous studies, coexposure of embryos to PCB-126 with the AHR antagonist and CYP1A inhibitor α-naphthoflavone decreased frequency and severity of deformities compared with embryos exposed to PCB-126 alone. In contrast, embryos coexposed to the PAHs with each of the CYP1A inhibitors tested were deformed with increased severity and frequency compared with embryos dosed with PAH alone. The mechanism by which inhibition of CYP1A increased embryotoxicity of the PAHs tested is not understood, but these results may be helpful in elucidating mechanisms by which PAHs are embryotoxic. Additionally, these results call into question additive models of PAH embryotoxicity for environmental PAH mixtures that contain both AHR agonists and CYP1A inhibitors

Bloom drivers of the potentially harmful dinoflagellate Prorocentrum minimum (Pavillard) Schiller in a south eastern temperate Australian estuary

© 2018 Elsevier Ltd Harmful algal blooms are an increasing concern in the estuarine reaches of the Hawkesbury-Nepean River, one of the largest coastal rivers systems in south eastern Australia. In the austral spring of 2016, an unprecedented bloom of the harmful mixotrophic dinoflagellate Prorocentrum minimum occurred in Berowra Creek (maximum cell abundance 1.9E+06 cells L−1, 89% of the total phytoplankton community), a major tributary of this river system. In response to this bloom, our study utilises an estuary-wide, thirteen-year time series of phytoplankton abundance and environmental data to examine the spatial and temporal patterns of this harmful alga and its potential bloom drivers in this system. P. minimum cell densities and environmental parameters varied over large spatial scales, with sites located in the main channel of the estuary significantly differing from those in the more urbanized tributary of Berowra Creek. Generalised additive modelling outputs suggested that blooms of P. minimum are complex, but generally corresponded to a spatial gradient of eutrophication and salinity, whereby P. minimum growth and concomitant high chlorophyll-a concentrations were enhanced at sites that were generally less saline and more eutrophic than others. Furthermore, temporal patterns suggested that blooms occurred abruptly and lasted up to three weeks, most often during the austral autumn to spring. While significant correlations were observed between rainfall and nutrients at all other sites, suggesting a pathway for nutrient availability, the association between rainfall and nutrient delivery was generally not observed in Berowra Creek (a 15-m deep site) suggesting that a continual supply of nutrients, coupled with unique bathymetry and water residence time at this site, are the most likely contributing factors to phytoplankton growth. This study presents the most comprehensive examination of P. minimum in any southern hemisphere estuary to date and highlights the importance of continued monitoring of HABs and the important role that anthropogenic inputs have in driving blooms of P. minimum in this oyster-growing river/estuary system

Effect of Oil on Cellulose Dissolution in the Ionic Liquid 1-Butyl-3-methyl Imidazolium Acetate

While ionic liquids (ILs) are well known to be excellent solvents for cellulose, the exact mechanism of dissolution has been a much disputed topic in recent years and is still not completely clear. In this work, we add to the current understanding and highlight the importance of hydrophobic interactions, through studying cellulose dissolution in mixtures of 1-butyl-3-methyl imidazolium acetate (BmimAc) and medium-chain triglyceride (MCT) oil. We demonstrate that the order in which constituents are mixed together plays a key role, through nuclear magnetic resonance (NMR) spectroscopic analysis. When small quantities of MCT oil (0.25–1 wt %) were introduced to BmimAc before cellulose, the effect on BmimAc chemical shift values was much more significant compared to when the cellulose was dissolved first, followed by oil addition. Rheological analysis also showed small differences in the viscosities of oil–cellulose–BmimAc solutions, depending on the order the constituents were added. On the other hand, no such order effect on the NMR results was observed when cellulose was replaced with cellobiose, suggesting that this observation is unique to the macromolecule. We propose that a cellulose–oil interaction develops but only when the cellulose structure has a sufficient degree of order and not when the cellulose is molecularly dispersed, since the hydrophobic cellulose plane is no longer intact. In all cases, cellulose–BmimAc–oil solutions were stable for at least 4 months. To our knowledge, this is the first work that investigates the effect of oil addition on the dissolving capacity of BmimAc and highlights the need for further re-evaluation of accepted mechanisms for cellulose dissolution in ILs

Advances in the use of microgels as emulsion stabilisers and as a strategy for cellulose functionalisation

Microgel particles have recently emerged as an alternative route to emulsion stabilisation. Classed as soft colloidal particles, their ability to swell to differing degrees in certain solvents and to rearrange once attached to an interface makes them highly suitable for systems requiring long-term stabilization, such as formulations in the food, agricultural, cosmetic and pharmaceutical industries. Microgels made with biocompatible polymers such as proteins and polysaccharides in particular offer an environmental advantage and currently form a very active area of research. Cellulose, being a natural, biodegradable polymer, is an attractive ingredient for gels and microgels. However, its use as a functional material is often somewhat hindered by its insolubility in water and most other organic solvents. Furthermore, the surface activity of cellulose has proven difficult to harness and therefore its ability to act as an emulsion stabiliser has been almost exclusively applied to oil-in-water (O/W) emulsions, with very few reports on its water in oil (W/O) activity. This review aims to summarise some of the recent progress made in the microgel field including their ability to act as emulsion stabilisers, with a focus on cellulose microgels (CMGs). A brief overview of cellulose processing is also given, describing the dissolution and reprecipitation routes used to functionalise cellulose without covalent modification and the potential for cellulose particles and CMGs to act as O/W and W/O emulsion stabilisers

Relationship between size and cellulose content of cellulose microgels (CMGs) and their water-in-oil emulsifying capacity

Soluble polysaccharides have been used extensively as gelling/thickening agents in emulsions, but they generally display weak surface activity. Insoluble polysaccharides such as cellulose can be converted to thickening agents and even emulsifiers, but generally only after considerable chemical modification. Here we use the ionic liquid (IL) 1-butyl-3-methyl imidazolium acetate (BmimAc) to dissolve and reprecipitate cellulose in the presence of oil, i.e., a physical process, to tune the cellulose properties. ILs have previously been used in this way to form hydrophobic (‘oily’) cellulose microgels (CMGs), potentially capable of stabilizing water-in-oil (W/O) emulsions. However, these previous CMGs were made via a ‘top-down’ method and were relatively large and polydisperse, giving limited stability to the W/O emulsions formed. Here we demonstrate how the CMG size can be drastically reduced via a ‘bottom-up’ approach and employing high-pressure homogenization (HPH), thus achieving sub-micron CMG particle sizes. This has previously been impossible with other reported IL-cellulose coagulation methods and the corresponding W/O emulsions were more stable. In addition, confocal and cryo-scanning electron microscopy (SEM) revealed that the surface coverage of these CMGs on droplets increased over time, which led to the formation of even thicker interfacial layers and further enhanced emulsion stability (at least 2 months). We also demonstrate unequivocally that the stability of the W/O emulsions is indeed due to the CMGs adsorbing via the Pickering mechanism, rather than forming a stabilizing cellulosic network in the continuous phase, thus providing a novel route to ‘green’ Pickering emulsions

Variations in the slope of the resolved star-forming main sequence: A tool for constraining the mass of star-forming regions

The correlation between galaxies' integrated stellar masses and star formation rates (the 'star formation main sequence', SFMS) is a well-established scaling relation. Recently, surveys have found a relationship between the star formation rate (SFR) and stellar mass surface densities on kpc and sub-kpc scales (the 'resolved SFMS', rSFMS). In this work, we demonstrate that the rSFMS emerges naturally in Feedback In Realistic Environments 2 (FIRE-2) zoom-in simulations of Milky Way-mass galaxies. We make SFR and stellar mass maps of the simulated galaxies at a variety of spatial resolutions and star formation averaging time-scales and fit the rSFMS using multiple methods from the literature. While the absolute value of the SFMS slope (αMS) depends on the fitting method, the slope is steeper for longer star formation time-scales and lower spatial resolutions regardless of the fitting method employed. We present a toy model that quantitatively captures the dependence of the simulated galaxies' αMS on spatial resolution and use it to illustrate how this dependence can be used to constrain the characteristic mass of star-forming clumps

Ice nucleation by fertile soil dusts: Relative importance of mineral and biogenic components

Agricultural dust emissions have been estimated to contribute around 20% to the global dust burden. In contrast to dusts from arid source regions, the ice-nucleating abilities of which have been relatively well studied, soil dusts from fertile sources often contain a substantial fraction of organic matter. Using an experimental methodology which is sensitive to a wide range of ice nucleation efficiencies, we have characterised the immersion mode ice-nucleating activities of dusts (d<11 μ m) extracted from fertile soils collected at four locations around England. By controlling droplet sizes, which ranged in volume from 10 to 10 L (concentration=0.02 to 0.1 wt% dust), we have been able to determine the ice nucleation behaviour of soil dust particles at temperatures ranging from 267K (-6°C) down to the homogeneous limit of freezing at about 237K (-36°C). At temperatures above 258K (-15°C) we find that the ice-nucleating activity of soil dusts is diminished by heat treatment or digestion with hydrogen peroxide, suggesting that a major fraction of the ice nuclei stems from biogenic components in the soil. However, below 258 K, we find that the ice active site densities tend towards those expected from the mineral components in the soils, suggesting that the inorganic fraction of soil dusts, in particular the K-feldspar fraction, becomes increasingly important in the initiation of the ice phase at lower temperatures. We conclude that dusts from agricultural activities could contribute significantly to atmospheric IN concentrations, if such dusts exhibit similar activities to those observed in the current laboratory study

A risk profile for identifying community-dwelling elderly with a highrisk of recurrent falling: results of a 3-year prospective study

Introduction: The aim of the prospective study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling. Materials and methods: The study was designed as a 3-year prospective cohort study. A total of 1365 community-dwelling persons, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam participated in the study. During an interview in 1995/1996, physical, cognitive, emotional and social aspects of functioning were assessed. A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly. Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up. Results: The incidence of recurrent falls at the 3-year follow-up point was 24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87 fractures that resulted from a fall, including 20 hip fractures, 21 wrist fractures and seven humerus fractures. Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling: two or more previous falls, dizziness, functional limitations, weak grip strength, low body weight, fear of falling, the presence of dogs/cats in the household, a high educational level, drinking 18 or more alcoholic consumptions per week and two interaction terms (high educationx18 or more alcohol consumptions per week and two or more previous falls x fear of falling) (AUC=0.71). Discussion: At a cut-off point of 5 on the total risk score (range 0-30), the model predicted recurrent falling with a sensitivity of 59% and a specificity of 71%. At a cut-off point of 10, the sensitivity and specificity were 31% and 92%, respectively. A risk profile including nine predictors that can easily be assessed seems to be a useful tool for the identification of community-dwelling elderly with a high risk of recurrent falling. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006

New insights into atypical Alzheimer's disease in the era of biomarkers

Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease