The long-term stability of a possible aqueous ammonium sulfate ocean inside Titan

We model the thermal evolution of a subsurface ocean of aqueous ammonium sulfate inside Titan using a parameterized convection scheme. The cooling and crystallization of such an ocean depends on its heat flux balance, and is governed by the pressure-dependent melting temperatures at the top and bottom of the ocean. Using recent observations and previous experimental data, we present a nominal model which predicts the thickness of the ocean throughout the evolution of Titan; after 4.5 Ga we expect an aqueous ammonium sulfate ocean 56 km thick, overlain by a thick (176 km) heterogeneous crust of methane clathrate, ice I and ammonium sulfate. Underplating of the crust by ice I will give rise to compositional diapirs that are capable of rising through the crust and providing a mechanism for cryovolcanism at the surface. We have conducted a parameter space survey to account for possible variations in the nominal model, and find that for a wide range of plausible conditions, an ocean of aqueous ammonium sulfate can survive to the present day, which is consistent with the recent observations of Titan's spin state from Cassini radar data [Lorenz, R.D., Stiles, B.W., Kirk, R.L., Allison, M.D., del Marmo, P.P., Iess, L., Lunine, J.I., Ostro, S.J., Hensley, S., 2008. Science 319, 1649–1651].

Aerosol forcing in the Climate Model Intercomparison Project (CMIP5) simulations by HadGEM2-ES and the role of ammonium nitrate

The latest Hadley Centre climate model, HadGEM2-ES, includes Earth system components such as interactive chemistry and eight species of tropospheric aerosols. It has been run for the period 1860–2100 in support of the fifth phase of the Climate Model Intercomparison Project (CMIP5). Anthropogenic aerosol emissions peak between 1980 and 2020, resulting in a present-day all-sky top of the atmosphere aerosol forcing of −1.6 and −1.4 W m−2 with and without ammonium nitrate aerosols, respectively, for the sum of direct and first indirect aerosol forcings. Aerosol forcing becomes significantly weaker in the 21st century, being weaker than −0.5 W m−2 in 2100 without nitrate. However, nitrate aerosols become the dominant species in Europe and Asia and decelerate the decrease in global mean aerosol forcing. Considering nitrate aerosols makes aerosol radiative forcing 2–4 times stronger by 2100 depending on the representative concentration pathway, although this impact is lessened when changes in the oxidation properties of the atmosphere are accounted for. Anthropogenic aerosol residence times increase in the future in spite of increased precipitation, as cloud cover and aerosol-cloud interactions decrease in tropical and midlatitude regions. Deposition of fossil fuel black carbon onto snow and ice surfaces peaks during the 20th century in the Arctic and Europe but keeps increasing in the Himalayas until the middle of the 21st century. Results presented here confirm the importance of aerosols in influencing the Earth's climate, albeit with a reduced impact in the future, and suggest that nitrate aerosols will partially replace sulphate aerosols to become an important anthropogenic species in the remainder of the 21st century.

Case study part 1: how to calculate appropriate deterministic long-term toxicity to exposure rates (TERs) for birds and mammals

In the European Union, first-tier assessment of the long-term risk to birds and mammals from pesticides is based on calculation of a deterministic long-term toxicity/exposure ratio(TERlt). The ratio is developed from generic herbivores and insectivores and applied to all species. This paper describes two case studies that implement proposed improvements to the way long-term risk is assessed. These refined methods require calculation of a TER for each of five identified phases of reproduction (phase-specific TERs) and use of adjusted No Observed Effect Levels (NOELs)to incorporate variation in species sensitivity to pesticides. They also involve progressive refinement of the exposure estimate so that it applies to particular species, rather than generic indicators, and relates spraying date to onset of reproduction. The effect of using these new methods on the assessment of risk is described. Each refinement did not necessarily alter the calculated TER value in a way that was either predictable or consistent across both case studies. However, use of adjusted NOELs always reduced TERs, and relating spraying date to onset of reproduction increased most phase-specific TERs. The case studies suggested that the current first-tier TERlt assessment may underestimate risk in some circumstances and that phase-specific assessments can help identify appropriate risk-reduction measures. The way in which deterministic phase-specific assessments can currently be implemented to enhance first-tier assessment is outlined.

Gut microbiome modulates the toxicity of hydrazine: a metabonomic study

The influence of gut microbiota on the toxicity and metabolism of hydrazine has been investigated in germ-free and ‘conventional’ Sprague Dawley rats using 1H NMR based metabonomic analysis of urine and plasma. Toxicity was more severe in germ-free rats compared with conventional rats for equivalent exposures indicating that bacterial presence altered the nature or extent of response to hydrazine and that the toxic response can vary markedly in the absence of a functional microbiome.

Cesium toxicity in Arabidopsis

Cesium (Cs) is chemically similar to potassium (K). However, although K is an essential element, Cs is toxic to plants. Two contrasting hypotheses to explain Cs toxicity have been proposed: (1) extracellular Cs+ prevents K+ uptake and, thereby, induces K starvation; and (2) intracellular Cs+ interacts with vital K+-binding sites in proteins, either competitively or noncompetitively, impairing their activities. We tested these hypotheses with Arabidopsis (Arabidopsis thaliana). Increasing the Cs concentration in the agar (Cs(agar)) on which Arabidopsis were grown reduced shoot growth. Increasing the K concentration in the agar (K(agad)) increased the Cs(agar) at which Cs toxicity was observed. However, although increasing Cs(agar) reduced shoot K concentration (K(shoot)), the decrease in shoot growth appeared unrelated to K(shoot) per se. Furthermore, the changes in gene expression in Cs-intoxicated plants differed from those of K-starved plants, suggesting that Cs intoxication was not perceived genetically solely as K starvation. In addition to reducing K(shoot) increasing Cs(agar) also increased shoot Cs concentration (Cs(shoot)), but shoot growth appeared unrelated to Cs(shoot) per se. The relationship between shoot growth and Cs(shoot)/Kt(shoot) suggested that, at a nontoxic Cs(shoot) growth was determined by K(shoot) but that the growth of Cs-intoxicated plants was related to the Cs(shoot)/K(shoot) quotient. This is consistent with Cs intoxication resulting from competition between K+ and Cs+ for K+-binding sites on essential proteins.

Curcumin protects organotypic hippocampal slice cultures 4 from Ab1–42 -induced synaptic toxicity

Increasing evidence demonstrates that beta-amyloid (Ab) is toxic to synapses, resulting in the progressive dismantling of neuronal circuits. Counteract the synaptotoxic effects of Ab could be particularly relevant for providing effective treatments for Alzheimer’s disease (AD). Curcumin was recently reported to improve learning and memory in animal models of AD. Little is currently known about the specific mechanisms by which Ab affects neuronal excitability and curcumin ameliorates synaptic transmission in the hippocampus. Organotypic hippocampal slice cultures exposed to Ab1–42 were used to study the neuroprotective effects of curcumin through a spectral analysis of multi-electrode array (MEA) recordings of spontaneous neuronal activity. Curcumin counteracted both deleterious effects of Ab; the initial synaptic dysfunction and the later neuronal death. The analysis of MEA recordings of spontaneous neuronal activity showed an attenuation of signal propagation induced by Ab before cell death and curcumin-induced alterations to local field potential (LFP) phase coherence. Curcumin-mediated attenuation of Ab-induced synaptic dysfunction involved regulation of synaptic proteins, namely phospho-CaMKII and phosphosynapsin I. Taken together, our results expand the neuroprotective role of curcumin to a synaptic level. The identification of these mechanisms underlying the effects of curcumin may lead to new targets for future therapies for AD.

Heme oxygenase-1 protects against Alzheimer’s amyloid-β1-42 induced toxicity via carbon monoxide production

Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer‟s disease (AD), catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediate cellular K+ efflux as an early step in the apoptotic cascade. Since apoptosis contributes to the neuronal loss associated with amyloid β peptide (Aβ) toxicity in AD, we investigated the protective effects of HO-1 and CO against Aβ1-42 toxicity in SH-SY5Y cells, employing cells stably transfected with empty vector or expressing the cellular prion protein, PrPc, and rat primary hippocampal neurons. Aβ1-42 (containing protofibrils) caused a concentrationdependent decrease in cell viability, attributable at least in part to induction of apoptosis, with the PrPc expressing cells showing greater susceptibility to Aβ1-42 toxicity. Pharmacological induction or genetic over-expression of HO-1 significantly ameliorated the effects of Aβ1-42. The CO-donor CORM-2 protected cells against Aβ1-42 toxicity in a concentration-dependent manner. Electrophysiological studies revealed no differences in the outward current pre- and post-Aβ1-42 treatment suggesting that K+ channel activity is unaffected in these cells. Instead, Aβ toxicity was reduced by the L-type Ca2+ channel blocker nifedipine, and by the CaMKKII inhibitor, STO-609. Aβ also activated the downstream kinase, AMP-dependent protein kinase (AMPK). CO prevented this activation of AMPK. Our findings indicate that HO-1 protects against Aβ toxicity via production of CO. Protection does not arise from inhibition of apoptosis-associated K+ efflux, but rather by inhibition of AMPK activation, which has been recently implicated in the toxic effects of Aβ. These data provide a novel, beneficial effect of CO which adds to its growing potential as a therapeutic agent.

Phosphate supply and arsenate toxicity in ectomycorrhizal fungi

Three species of ectomycorrhizal fungi (Hebeloma crustuliniforme, Suillus variegatus and Cenococcum geophilum) were grown in axenic culture amended with range of AsO43– concentration under three different PO43– regimes. The fungi exhibited different growth responses to AsO43– that varied with PO43– concentration. Suillus variegatus showed the greatest sensitivity to AsO43–, with growth almost completely inhibited in the presence of AsO43– under the lower two PO43– treatments. Under the highest PO43– treatment however, growth was enhanced and S. variegatus was able to persist at AsO43– concentrations of up to 4 mM. Hebeloma crustuliniforme also showed high sensitivity to AsO43– especially at low PO43– concentration. The two higher PO43– treatments had an ameliorating effect on AsO43– toxicity in H. crustuliniforme. This demonstrates the ability of PO43– to alleviate AsO43– toxicity. The response from S. variegatus and H. crustuliniforme, both basidiomycetes, was in contrast to the ascomycete C. geophilum. This fungus demonstrated tolerance to AsO43– when grown in culture solution and PO43– did not have an ameliorating effect on AsO43– toxicity in C. geophilum.

The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants.