Dose-dependent synergistic and antagonistic mutation responses of binary mixtures of the environmental carcinogen benzo[a]pyrene with food-derived carcinogens

Cooking food at high temperatures produces genotoxic chemicals and there is concern about their impact on human health. DNA damage caused by individual chemicals has been investigated but few studies have examined the consequences of exposure to mixtures as found in food. The current study examined the mutagenic response to binary mixtures of benzo[a]pyrene (BaP) with glycidamide (GA), BaP with acrylamide (AC), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) with GA at human-relevant concentrations (sub-nM). The metabolically competent human MCL-5 cells were exposed to these chemicals individually or in mixtures and mutagenicity was assessed at the thymidine kinase (TK) locus. Mixture exposures gave dose-responses that differed from those for the individual chemicals; for the BaP-containing mixtures, an increased mutation frequency (MF) at low concentration combinations that were not mutagenic individually, and decreased MF at higher concentration combinations, compared to the calculated predicted additive MF of the individual chemicals. In contrast, the mixture of PhIP with GA did not increase MF above background levels. These data suggest BaP is driving the mutation response and that metabolic activation plays a role; in mixtures with BaP the increased/decreased MF above/below the expected additive MF the order is PhIP > AC > GA. The increase in MF at some low concentration combinations that include BaP is interesting and supports our previous work showing a similar response for BaP with PhIP, confirming this response is not limited to the BaP/PhIP combination. Moreover, the lack of a mutation response for PhIP with GA relative to the response of the individual chemicals at equivalent doses is interesting and may represent a potential avenue for reducing the risk of exposure to environmental carcinogens; specifically, removal of BaP from the mixture may reduce the mutation effect, although in the context of food this would be significantly challenging

Istraživanje oksidativnog stresa i genotoksičnosti slatkovodnih riba Cyprinus Carpio nakon izloženosti subletalnoj dozi triazofosa

Triazophos (TAP), an organophosphorus insecticide, is widely used in agricultural practice for controlling various insect pests. The present research work aimed to elucidate the impact of TAP on the antioxidant status and DNA content of the freshwater fish Cyprinus carpio. The fish were grouped into batches (n=6) and received a sublethal dose of 0.3mg/L for a duration of 1 (E1), 10 (E2), 20 (E3) and 30 days (E4). Another group, devoid of any toxicant, was maintained as the control (C). Changes in the enzymatic threshold of the selected antioxidants and malondialdehyde (MDA) levels suggested the conformation of oxidative stress in the livers of the freshwater fish C. carpio due to TAP exposure. Additionally, comet assays and micronucleus tests performed on the peripheral blood of the fish suggested increased damage in the form of the percentage of tail DNA formation and a high frequency of micronucleus as compared to the control. A positive correlation was seen between the decline in antioxidant activity, the elevation in MDA and the comet length and micronucleus frequency. The study thus highlights the impact of TAP on antioxidant levels in the livers and genotoxicity in the blood of the freshwater fish C. carpio. The findings of the study confirm that the antioxidant status, along with the comet assay and micronucleus tests could be used as tools in determining the potential genotoxicity due to the TAP impact. It is therefore suggested that extensive use of TAP should be avoided as it may contribute to the decline in the C. carpio population in its natural habitats.Triazofos (TAP) je organofosforni insekticid koji se široko koristi u poljoprivrednoj praksi za suzbijanje raznih štetnih insekata. Cilj ovog istraživanja bio je procjeniti utjecaj TAP-a na antioksidativni status i DNK slatkovodne ribe Cyprinus carpio. Ribe su razvrstane u skupine (n = 6) u kojima su primale subletalnu dozu TAP-a 0.3mg/L u trajanju od 1 (E1), 10 (E2), 20 (E3) i 30 dana (E4). Druga skupina, koja nije izložena TAP-u, smatrana je kontrolnom (C). Promjene enzimskog praga odabranih antioksidansa i razina malondialdehida (MDA) potvrdile su da izloženost TAP-u izaziva oksidativni stres u jetrama slatkovodne ribe C. carpio. Osim toga, komet analize i mikronukleusni testovi provedeni na perifernoj krvi riba ukazali su da u eksperimentalnih skupina u odnosu na kontrolu postoji povećani postotak oštećenja u obliku DNK repa i povećane učestalosti mikronukleusa. Uočena je pozitivna korelacija između pada antioksidativne aktivnosti, porasta MDA, duljine kometa i učestalosti mikronukleusa. Uzevši u obzir navedeno, istraživanje naglašava utjecaj TAP-a na razine antioksidansa u jetrama i genotoksičnost u krvi slatkovodne ribe C. carpio. Rezultati potvrđuju da se antioksidativni status, zajedno s kometnim testom i mikronukleusnim testovima, može koristiti kao alat za određivanje potencijalne genotoksičnosti TAP-a. Stoga se predlaže izbjegavanje široke uporaba TAP-a koja bi mogla doprinijeti smanjenju populacije C. carpio u njezinim prirodnim staništima

A Categorical Approach to Groupoid Frobenius Algebras

In this paper, we show that \C{G}-Frobenius algebras (for \C{G} a finite groupoid) correspond to a particular class of Frobenius objects in the representation category of D(k[\C{G}]), where D(k[\C{G}]) is the Drinfeld double of the quantum groupoid k[\C{G}].Comment: final version; to appear in Applied Categorical Structure

Representing crop rotations in life cycle assessment: a review of legume LCA studies

There is an imperative to accurately assess the environmental sustainability of crop system interventions in the context of food security and climate change. Previous studies have indicated that the incorporation of legumes into cereal rotations could reduce overall environmental burdens from cropping systems. However, most LCA studies focus on individual crops and miss environmental consequences of inter-annual crop sequence and nutrient cycling effects. This review investigates state-of-the-art representation of inter-crop rotation effects within legume LCA studies

First-principles modeling of strain in perovskite ferroelectric thin films

We review the role that first-principles calculations have played in understanding the effects of substrate-imposed misfit strain on epitaxially grown perovskite ferroelectric films. We do so by analyzing the case of BaTiO$_3$, complementing our previous publications on this subject with unpublished data to help explain in detail how these calculations are done. We also review similar studies in the literature for other perovskite ferroelectric-film materials.Comment: 14 pages, submitted to Phase Transition

A Neuroanatomical Signature for Schizophrenia Across Different Ethnic Groups

Schizophrenia is a disabling clinical syndrome found across the world. While the incidence and clinical expression of this illness are strongly influenced by ethnic factors, it is unclear whether patients from different ethnicities show distinct brain deficits. In this multicentre study, we used structural Magnetic Resonance Imaging to investigate neuroanatomy in 126 patients with first episode schizophrenia who came from 4 ethnically distinct cohorts (White Caucasians, African-Caribbeans, Japanese, and Chinese). Each patient was individually matched with a healthy control of the same ethnicity, gender, and age (±1 year). We report a reduction in the gray matter volume of the right anterior insula in patients relative to controls (P < .05 corrected); this reduction was detected in all 4 ethnic groups despite differences in psychopathology, exposure to antipsychotic medication and image acquisition sequence. This finding provides evidence for a neuroanatomical signature of schizophrenia expressed above and beyond ethnic variations in incidence and clinical expression. In light of the existing literature, implicating the right anterior insula in bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety, we speculate that the neuroanatomical deficit reported here may represent a transdiagnostic feature of Axis I disorders

White matter integrity as a predictor of response to treatment in first episode psychosis

The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response

Net Zero requires ambitious greenhouse gas emission reductions on beef and sheep farms coordinated with afforestation and other land use change measures

CONTEXT: The UK Climate Change Committee has recommended a 64% reduction in greenhouse gas emissionsfrom the agriculture and land-use sector to meet the 2050 Net Zero target in the UK. However, it is unclear howthis reduction can be achieved at a farm level.OBJECTIVE: Using detailed real farm data and novel modelling approaches, we investigated the managementinterventions and afforestation that would be required to deliver Net Zero within the farm boundary.METHODS: Baseline carbon footprints were calculated for twenty Welsh beef and sheep farms using the Agrecalccarbon calculator, whilst carbon sequestration was estimated using Bangor University’s Carbon FootprintingTool. Scenarios were created to determine the emissions reductions achievable on each farm through implementationof cost-effective mitigation measures. Mitigation measures and their abatement potentials weresourced from the most recent UK Marginal Abatement Cost Curve, which allow emissions to be reduced mostlythrough improvements in efficiency thus maintaining the production of the system. Area footprints werecalculated for production, with and without offset (afforested) areas needed to achieve Net Zero

Gene × Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study

BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 – 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer