BRCA1 protein dose-dependent risk for embryonic oxidative DNA damage, embryopathies and neurodevelopmental disorders with and without ethanol exposure.

Although widely known as a tumor suppressor, the breast cancer 1 susceptibility protein (BRCA1) is also important in development, where it regulates fetal DNA repair pathways that protect against DNA damage caused by physiological and drug-enhanced levels of reactive oxygen species (ROS). We previously showed that conditional heterozygous (+/-) knockout (cKO) mouse embryos with a minor 28% BRCA1 deficiency developed normally in culture, but when exposed to the ROS-initiating drug, alcohol (ethanol, EtOH), exhibited embryopathies not evident in wild-type (+/+) littermates. Herein, we characterized a directBrca1 +/- knockout (KO) model with a 2-fold greater (58%) reduction in BRCA1 protein vs. the cKO model. We also characterized and compared learning & memory deficits in both the cKO and KO models. Even saline-exposed Brca1 +/- vs. +/+ KO progeny exhibited enhanced oxidative DNA damage and embryopathies in embryo culture and learning & memory deficits in females in vivo, which were not observed in the cKO model, revealing the potential pathogenicity of physiological ROS levels. The embryopathic EtOH concentration for cultured direct KO embryos was half that for cKO embryos, and EtOH affected Brca1 +/+ embryos only in the direct KO model. The spectrum and severity of EtOH embryopathies in culture were greater in both Brca1 +/- vs. +/+ embryos, and direct KO vs. cKO +/- embryos. Motor coordination deficits were evident in both male and female Brca1 +/- KO progeny exposed in utero to EtOH. The results in our direct KO model with a greater BRCA1 deficiency vs. cKO mice provide the first evidence for BRCA1 protein dose-dependent susceptibility to developmental disorders caused by physiological and drug-enhanced oxidative stress.

The UN Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) - An ocean science-policy interface standing the test of time.

Addressing the wide range of marine pollution problems facing the global ocean requires a continual transfer of credible, relevant and timely scientific information to policy and decision makers in coastal and ocean management. The United Nations GESAMP (Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection) is a long-standing scientific advisory group providing such information on a wide range of marine topics and emerging issues of concern to ten UN Sponsoring Organizations. This paper presents an overview of GESAMPs operation and examples of its current work. The group's scientific output is often cited by national governments, inter-governmental groups, and a range of non-governmental groups. Given the growing concerns about ocean health and the impacts of many stressors in an era of climate change, the development of timely and effective ocean policy and decision making would benefit from wider recognition and application of GESAMPs work.

System confluence and the reinvention of automobility.

The aim of the paper is to provide a longitudinal account of the emergence and stabilization of the automobility system and to assess the contemporary state of the system in the early stages of an ongoing sustainability transition. The production, use, and disposal of cars, in a pervasive global automobility system, are examined to reveal and explain the growing sustainability significance of overlaps with other systems. System-to-system confluence to varying degrees is ongoing with electricity, housing, aerospace, and information, software, and communications systems. The interfaces between multiple systems are evidenced by contestation for legitimacy via technological innovation and organizational experimentation. The result is uncertainty among key actors and stakeholders, institutional reforms, diverse corporate strategies, and emergent societal practices and behaviors. The paper thereby provides a contextualized account of the tension between barriers to change that may preserve the coherence of the automobility system and differential boundary effects arising from the impact of other production-consumption systems that may result in regime fragmentation. Confluence with other systems may resolve some sustainability contradictions but will also create new ones. Appeal to sustainability science will be key to evaluating how far existing sustainability problems will be resolved, and how far new ones will emerge in the automobility transition.

Altered Epigenetic Marks and Gene Expression in Fetal Brain, and Postnatal Behavioural Disorders, Following Prenatal Exposure of Ogg1 Knockout Mice to Saline or Ethanol.

Oxoguanine glycosylase 1 (OGG1) is widely known to repair the reactive oxygen species (ROS)-initiated DNA lesion 8-oxoguanine (8-oxoG), and more recently was shown to act as an epigenetic modifier. We have previously shown that saline-exposed Ogg1 -/- knockout progeny exhibited learning and memory deficits, which were enhanced by in utero exposure to a single low dose of ethanol (EtOH) in both Ogg1 +/+ and -/- progeny, but more so in Ogg1 -/- progeny. Herein, OGG1-deficient progeny exposed in utero to a single low dose of EtOH or its saline vehicle exhibited OGG1- and/or EtOH-dependent alterations in global histone methylation and acetylation, DNA methylation and gene expression (Tet1 (Tet Methylcytosine Dioxygenase 1), Nlgn3 (Neuroligin 3), Hdac2 (Histone Deacetylase 2), Reln (Reelin) and Esr1 (Estrogen Receptor 1)) in fetal brains, and behavioural changes in open field activity, social interaction and ultrasonic vocalization, but not prepulse inhibition. OGG1- and EtOH-dependent changes in Esr1 and Esr2 mRNA and protein levels were sex-dependent, as was the association of Esr1 gene expression with gene activation mark histone H3 lysine 4 trimethylation (H3K4me3) and gene repression mark histone H3 lysine 27 trimethylation (H3K27me3) measured via ChIP-qPCR. The OGG1-dependent changes in global epigenetic marks and gene/protein expression in fetal brains, and postnatal behavioural changes, observed in both saline- and EtOH-exposed progeny, suggest the involvement of epigenetic mechanisms in developmental disorders mediated by 8-oxoG and/or OGG1. Epigenetic effects of OGG1 may be involved in ESR1-mediated gene regulation, which may be altered by physiological and EtOH-enhanced levels of ROS formation, possibly contributing to sex-dependent developmental disorders observed in Ogg1 knockout mice. The OGG1- and EtOH-dependent associations provide a basis for more comprehensive mechanistic studies to determine the causal involvement of oxidative DNA damage and epigenetic changes in ROS-mediated neurodevelopmental disorders.

Introducing a Dynamic Reconstruction Methodology for Multilayered Structures in Atom Probe Tomography.

Atom probe tomography (APT) is a powerful three-dimensional nanoanalyzing microscopy technique considered key in modern materials science. However, progress in the spatial reconstruction of APT data has been rather limited since the first implementation of the protocol proposed by Bas et al. in 1995. This paper proposes a simple semianalytical approach to reconstruct multilayered structures, i.e., two or more different compounds stacked perpendicular to the analysis direction. Using a field evaporation model, the general dynamic evolution of parameters involved in the reconstruction of this type of structure is estimated. Some experimental reconstructions of different structures through the implementation of this method that dynamically accommodates variations in the tomographic reconstruction parameters are presented. It is shown both experimentally and theoretically that the depth accuracy of reconstructed APT images is improved using this method. The method requires few parameters in order to be easily usable and substantially improves atom probe tomographic reconstructions of multilayered structures.

Breast cancer 1 (BRCA1) protection in altered gene expression and neurodevelopmental disorders due to physiological and ethanol-enhanced reactive oxygen species formation.

The breast cancer 1 (Brca1) susceptibility gene regulates the repair of reactive oxygen species (ROS)-mediated DNA damage, which is implicated in neurodevelopmental disorders. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), including abnormal brain function, associated with enhanced ROS-initiated DNA damage. Herein, oxidative DNA damage in fetal brains and neurodevelopmental disorders were enhanced in saline-exposed +/- vs. +/+ Brca1 littermates. A single EtOH exposure during gestation further enhanced oxidative DNA damage, altered the expression of developmental/DNA damage response genes in fetal brains, and resulted in neurodevelopmental disorders, all of which were BRCA1-dependent. Pretreatment with the ROS inhibitor phenylbutylnitrone (PBN) blocked DNA damage and some neurodevelopmental disorders in both saline- and EtOH-exposed progeny, corroborating a ROS-dependent mechanism. Fetal BRCA1 protects against altered gene expression and neurodevelopmental disorders caused by both physiological and EtOH-enhanced levels of ROS formation. BRCA1 deficiencies may enhance the risk for FASD.

Atomistic simulations on the carbidisation processes in Pd nanoparticles.

The formation of interstitial PdC x nanoparticles (NPs) is investigated through DFT calculations. Insights on the mechanisms of carbidisation are obtained whilst the material's behaviour under conditions of increasing C-concentration is examined. Incorporation of C atoms in the Pd octahedral interstitial sites is occurring through the [111] facet with an activation energy barrier of 19.3-35.7 kJ mol-1 whilst migration through the [100] facet corresponds to higher activation energy barriers of 124.5-127.4 kJ mol-1. Furthermore, interstitial-type diffusion shows that C will preferentially migrate and reside at the octahedral interstitial sites in the subsurface region with limited mobility towards the core of the NP. For low C-concentrations, migration from the surface into the interstitial sites of the NPs is thermodynamically favored, resulting in the formation of interstitial carbide. Carbidisation reaction energies are exothermic up to 11-14% of C-concentration and slightly vary depending on the shape of the structure. The reaction mechanisms turn to endothermic for higher concentration levels showing that C will preferentially reside on the surface making the interstitial carbide formation unfavorable. As experimentally observed, our simulations confirm that there is a maximum concentration of C in Pd carbide NPs opening the way for further computational investigations on the activity of Pd carbides in directed catalysis.

A comparative study on the stability of the furfural molecule on the low index Ni, Pd and Pt surfaces.

We present a comparative density functional theory investigation of the furfural (Ff) molecule on the low index Ni, Pd and Pt surfaces to understand its geometrical and electronic properties to gain mechanistic insights into the experimentally measured catalytic reactivities of these metal catalysts. We show that the number of metal d-states, which hybridize with the nearest C and O p-orbitals of the Ff molecule, can be used to explain the stability of the Ff molecule on these surfaces. We find that the hybridization between atoms with higher electronegativity and the metal d-states plays a crucial role in determining the stability of these systems. Furthermore, we also find electron transfer from metal to the Ff molecule on the Ni and Pd surfaces, with a reverse process occurring on the Pt surface.

DNA Damage and Repair and Epigenetic Modification in the Role of Oxoguanine Glycosylase 1 in Brain Development.

Oxoguanine glycosylase 1 (OGG1) repairs the predominant reactive oxygen species-initiated DNA lesion 8-oxoguanine. Human OGG1 polymorphisms resulting in reduced DNA repair associate with an increased risk for disorders like cancer and diabetes, but the role of OGG1 in brain development is unclear. Herein, we show that Ogg1 knockout mice at 2-3 months of age exhibit enhanced gene- and sex-dependent DNA damage (strand breaks) and decreased epigenetic DNA methylation marks (5-methylcytosine, 5-hydroxymethylcytosine), both of which were associated with increased cerebellar calbindin levels, reduced hippocampal postsynaptic function, altered body weight with age and disorders of brain function reflected in behavioral tests for goal-directed repetitive behavior, anxiety and fear, object recognition and spatial memory, motor coordination and startle response. These results suggest that OGG1 plays an important role in normal brain development, possibly via both its DNA repair activity and its role as an epigenetic modifier, with OGG1 deficiencies potentially contributing to neurodevelopmental disorders.

Sex- and OGG1-dependent reversal of in utero ethanol-initiated changes in postnatal behaviour by neonatal treatment with the histone deacetylase inhibitor trichostatin A (TSA) in oxoguanine glycosylase 1 (Ogg1) knockout mice.

Oxoguanine glycosylase 1 (OGG1) is both a DNA repair enzyme and an epigenetic modifier. We assessed behavioural abnormalities in OGG1-deficient progeny exposed once in utero to a low dose of ethanol (EtOH) and treated postnatally with a global histone deacetylase inhibitor, trichostatin A (TSA). The goal of this study was to determine if neurodevelopmental disorders initiated in the fetal brain by in utero exposure to EtOH could be mitigated by postnatal treatment with TSA. EtOH and TSA alone improved preference for novel location (short-term, 90 min) and novel object (long-term, 24 h) sex- and OGG1-dependently. Combined EtOH/TSA treatment reversed these effects in the short-term novel location test sex- and OGG1-dependently. In females but not males, the incidence of high shredders of nesting material was not altered by either TSA or EtOH alone, but was reduced by combined EtOH/TSA treatment in +/+ progeny. Similar but non-significant effects were observed in Ogg1 -/- females. Accelerated rotarod performance was enhanced by both EtOH and TSA alone in only male Ogg1 +/+ but not -/- progeny, and was not altered by combined EtOH/TSA exposure. The OGG1-dependent effects of EtOH and TSA particularly on novel location and the incidence of high shredders, and the reversal of EtOH effects on these parameters by combined EtOH/TSA treatment, suggests both xenobiotics may alter behaviour via a mechanism involving OGG1 acting as an epigenetic modifier, in addition to repairing DNA damage. These preliminary results suggest that the postnatal use of more selective epigenetic modifying agents may constitute a novel strategy for mitigating some components of ROS-initiated neurodevelopmental disorders.

The leatherback turtle (Dermochelys coriacea) and plastics in the Northwest Atlantic ocean: A hazard assessment.

Atlantic leatherback turtles are faced with multiple threats, such as ship strikes, pollution and predation, throughout their annual migratory routes in the Northwest (NW) Atlantic. The risks associated with encounters with floating and submerged plastic debris are currently unknown. This study is a hazard assessment of plastics for this turtle's sub-population, using 2010-2019 data from the national Great Canadian Shoreline Cleanup (GSCS) program, therefore potential exposure, and published evidence on the interactions of plastics and leatherbacks, hence potential effects. The type of plastic items and their abundance along shorelines of three Atlantic Provinces - Nova Scotia (NS), Prince Edward Island (PEI), Newfoundland and Labrador (NL) - were evaluated and compared to plastic items known to interact with leatherbacks. During the 2010-2019 period, a total of 220,590 plastic items were collected from 578 sites, representing 1264 km of shoreline. Plastic bags and rope are in the top ten most common items found on shorelines of NS, PEI, and NL. Pot gear and trap nets are in the top ten for PEI and are the 14th most common plastic item found on all shorelines. Cigarette debris is also commonly found. From the literature, plastic bags, pot gear and trap nets, and rope are known to adversely affect leatherbacks. Assuming that a large proportion of the shoreline debris comes in from the sea, after being in coastal waters for unknown periods, the study shows that such items pose a hazard to leatherbacks through ingestion and entanglement, based on published studies. Evidence is now needed on actual exposure at sea to the most common items to establish the ecological risk of plastics to these turtles in NW Atlantic waters.

Novel mechanisms in alcohol neurodevelopmental disorders via BRCA1 depletion and BRCA1-dependent NADPH oxidase regulation.

The breast cancer 1 protein (BRCA1) facilitates DNA repair, preventing embryolethality and protecting the fetus from reactive oxygen species (ROS)-induced developmental disorders mediated by oxidatively damaged DNA. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), characterized by aberrant behaviour and enhanced ROS formation and proteasomal protein degradation. Herein, ROS-producing NADPH oxidase (NOX) activity was higher in Brca1 +/- vs. +/+ fetal and adult brains, and further enhanced by a single EtOH exposure. EtOH also enhanced catalase and proteasomal activities, while conversely reducing BRCA1 protein levels without affecting Brca1 gene expression. EtOH-initiated adaptive postnatal freezing behaviour was lost in Brca1 +/- progeny. Pretreatment with the free radical spin trap and ROS inhibitor phenylbutylnitrone blocked all EtOH effects, suggesting ROS-dependent mechanisms. This is the first in vivo evidence of NOX regulation by BRCA1, and of EtOH-induced, ROS-mediated depletion of BRCA1, revealing novel mechanisms of BRCA1 protection in FASD.

Disrupting transitions: Qualitatively modelling the impact of Covid-19 on UK food and mobility provision.

The 2020 Covid-19 pandemic provides an empirical testing ground for assessing the impact of critical events on societal transitions. Such events are typically seen as exogenous to the transition process, an assumption which is investigated in this paper. Using a qualitative system dynamics modelling approach we conceptualize transition pathways as sets of interacting sequences of events. This enables the analysis of event sequences that constitute the evolving pandemic as impacting on those pathways. We apply this approach to the provision of (auto)mobility and food in the UK. This shows the way in which the pandemic has had a differential effect on ongoing transitions in both systems, sometimes slowing them down, and sometimes accelerating them. In addition, it reveals how it has established new transition pathways. The empirical work further shows how qualitative modelling with system dynamics facilitates an explicit and systematic comparative analysis of transition case studies.

Spatial Profiling of a Pd/Al2O3 Catalyst during Selective Ammonia Oxidation.

The utilization of operando spectroscopy has allowed us to watch the dynamic nature of supported metal nanoparticles. However, the realization that subtle changes to environmental conditions affect the form of the catalyst necessitates that we assess the structure of the catalyst across the reactant/product gradient that exists across a fixed bed reactor. In this study, we have performed spatial profiling of a Pd/Al2O3 catalyst during NH3 oxidation, simultaneously collecting mass spectrometry and X-ray absorption spectroscopy data at discrete axial positions along the length of the catalyst bed. The spatial analysis has provided unique insights into the structure-activity relationships that govern selective NH3 oxidation-(i) our data is consistent with the presence of PdN x after the spectroscopic signatures for bulk PdN x disappear and that there is a direct correlation to the presence of this structure and the selectivity toward N2; (ii) at high temperatures, ≥400 °C, we propose that there are two simultaneous reaction pathways-the oxidation of NH3 to NO x by PdO and the subsequent catalytic reduction of NO x by NH3 to produce N2. The results in this study confirm the structural and catalytic diversity that exists during catalysis and the need for such an understanding if improvements to important emission control technologies, such as the selective catalytic oxidation of NH3, are to be made.

The electronic structure, surface properties, and in situ N2O decomposition of mechanochemically synthesised LaMnO3.

The use of mechanochemistry to prepare catalytic materials is of significant interest; it offers an environmentally beneficial, solvent-free, route and produces highly complex structures of mixed amorphous and crystalline phases. This study reports on the effect of milling atmosphere, either air or argon, on mechanochemically prepared LaMnO3 and the catalytic performance towards N2O decomposition (deN2O). In this work, high energy resolution fluorescence detection (HERFD), X-ray absorption near edge structure (XANES), X-ray emission, and X-ray photoelectron spectroscopy (XPS) have been used to probe the electronic structural properties of the mechanochemically prepared materials. Moreover, in situ studies using near ambient pressure (NAP)-XPS, to follow the materials during catalysis, and high pressure energy dispersive EXAFS studies, to mimic the preparation conditions, have also been performed. The studies show that there are clear differences between the air and argon milled samples, with the most pronounced changes observed using NAP-XPS. The XPS results find increased levels of active adsorbed oxygen species, linked to the presence of surface oxide vacancies, for the sample prepared in argon. Furthermore, the argon milled LaMnO3 shows improved catalytic activity towards deN2O at lower temperatures compared to the air milled and sol-gel synthesised LaMnO3. Assessing this improved catalytic behaviour during deN2O of argon milled LaMnO3 by in situ NAP-XPS suggests increased interaction of N2O at room temperature within the O 1s region. This study further demonstrates the complexity of mechanochemically prepared materials and through careful choice of characterisation methods how their properties can be understood.

Reflecting on an anniversary. The 1970 SS Arrow oil spill in Chedabucto Bay, Nova Scotia, Canada.

Fifty years ago, the tanker SS Arrow ran aground in Chedabucto Bay on the east coast of Canada, causing a massive spill of Bunker C oil in winter conditions. This article reflects on this anniversary, briefly describing the spill response and the considerable follow-up research over five decades on the fate and effects of oils spilled in northern cold marine waters. Importantly, the spill led to considerable work in Canada on spill control and bioremediation measures, and advice about oil spills as a marine pollutant of global importance.

Al-doped Fe2O3 as a support for molybdenum oxide methanol oxidation catalysts.

We have made high surface area catalysts for the selective oxidation of methanol to formaldehyde. This is done in two ways - (i) by doping haematite with Al ions, to increase the surface area of the material, but which itself is unselective and (ii) by surface coating with Mo which induces high selectivity. Temperature programmed desorption (TPD) of methanol shows little difference in surface chemistry of the doped haematite from the undoped material, with the main products being CO2 and CO, but shifted to somewhat higher desorption temperature. However, when Mo is dosed onto the haematite surface, the chemistry changes completely to show mainly the selective product, formaldehyde, with no CO2 production, and this is little changed up to 10% Al loading. But at 15 wt% Al, the chemistry changes to indicate the presence of a strongly acidic function at the surface, with additional dimethyl ether and CO/CO2 production characteristic of the presence of alumina. Structurally, X-ray diffraction (XRD) shows little change over the range 0-20% Al doping, except for some small lattice contraction, while the surface area increases from around 20 to 100 m2 g-1. Using X-ray absorption spectroscopy (XAS) it is clear that, at 5% loading, the Al is incorporated into the Fe2O3 corundum lattice, which has the same structure as α-alumina. By 10% loading then it appears that the alumina starts to nano-crystallise within the haematite lattice into the γ form. At higher loadings, there is evidence of phase separation into separate Al-doped haematite and γ-alumina. If we add 1 monolayer equivalent of Mo to the surface there is already high selectivity to formaldehyde, but little change in structure, because that monolayer is isolated at the surface. However, when three monolayers equivalent of Mo is added, we then see aluminium molybdate type signatures in the XANES spectra at 5% Al loading and above. These appear to be in a sub-surface layer with Fe molybdate, which we interpret as due to Al substitution into ferric molybdate layers immediately beneath the topmost surface layer of molybdena. It seems like the separate γ-alumina phase is not covered by molybdena and is responsible for the appearance of the acid function products in the TPD.

Monitoring chemical contaminants in the Gulf of Maine, using sediments and mussels (Mytilus edulis): An evaluation.

The objective of this paper is to determine whether contaminant data on mussels and sediments can be used interchangeably, or not, when assessing the degree of anthropogenic contamination of a water body. To obtain adequate coverage of the entire Gulf of Maine, Bay of Fundy sediment samples were collected, analyzed and combined with similar data from four coastal monitoring programs. This required careful interpretation but provided robust results consistent with published literature. A strong correspondence was found between sediment and mussel concentrations for polycyclic aromatic hydrocarbons, moderate to weak correspondence for polychlorinated biphenyls, and except for mercury and zinc, little to no correspondence was found for metals. We conclude that mussel contaminant data are likely sufficient for providing information on the spatial and temporal distribution of chemical contaminants, in coastal waters, under a broad range of environmental conditions and contaminant levels, and unlike sediments, provide direct information on contaminant bioavailability.

In situ K-edge X-ray absorption spectroscopy of the ligand environment of single-site Au/C catalysts during acetylene hydrochlorination.

The replacement of HgCl2/C with Au/C as a catalyst for acetylene hydrochlorination represents a significant reduction in the environmental impact of this industrial process. Under reaction conditions atomically dispersed cationic Au species are the catalytic active site, representing a large-scale application of heterogeneous single-site catalysts. While the metal nuclearity and oxidation state under operating conditions has been investigated in catalysts prepared from aqua regia and thiosulphate, limited studies have focused on the ligand environment surrounding the metal centre. We now report K-edge soft X-ray absorption spectroscopy of the Cl and S ligand species used to stabilise these isolated cationic Au centres in the harsh reaction conditions. We demonstrate the presence of three distinct Cl species in the materials; inorganic Cl-, Au-Cl, and C-Cl and how these species evolve during reaction. Direct evidence of Au-S interactions is confirmed in catalysts prepared using thiosulfate precursors which show high stability towards reduction to inactive metal nanoparticles. This stability was clear during gas switching experiments, where exposure to C2H2 alone did not dramatically alter the Au electronic structure and consequently did not deactivate the thiosulfate catalyst.