New synthetic compounds as inhibitors of mycotoxin synthesis

Ochratoxin A (OTA) is a mycotoxin produced by some Aspergillus and Penicillium species which is often detected in beer, cereals, coffee, feeds, figs, sultanas and wine. Some fungicides have been found to be effective in preventing fungal growth, but, in other cases, an increase in the synthesis of mycotoxins was reported. Also, the pressure to use less harmful compounds to the environment stimulates the exploration of new and more benign compounds. Synthetic compounds were tested on the growth and OTA production of one strain of A. alliaceus, A. ochraceus, A. carbonarius and A. niger. These new synthetic compounds have a linear structure incorporating urea and/or a phenolic unit. Fungi were grown in yeast extract sucrose (YES) medium supplemented with 50 μM to 200 μM of each one of 20 test compounds in triplicate, for 6 days. Growth was recorded by measuring the diameter of colonies every 24 hours, and OTA was quantified after 5 days of growth using HPLC and fluorescence detection. Growth of the A. ochraceus and the A. carbonarius strains were not inhibited by most of these compounds. However, some led to a decrease in OTA detection. Compounds without the phenolic unit were found to be less effective, while those compounds with urea and phenolic units were the most effective. Growth of the A. alliaceus and of the A. niger strains were inhibited by compound-X by 22 and 27% respectively. This approach will lead to the selection of functional groups able to inhibit the synthesis of OTA which could be incorporated into more powerful antifungal compounds.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/11228/2002, SFRH/BD/3185/2000, SFRH/BPD/12044/2003

Radiosynthesis and in vivo evaluation of a 18F-labelled styryl-benzoxazole derivative for β-amyloid targeting

The formation of β-amyloid deposits is considered a histopathological feature of Alzheimer′s disease (AD). In vivo molecular imaging by means of amyloid-avid radiotracers will allow for an early and conclusive diagnostic of AD. Herein, we describe the radiosynthesis of the radiofluorinated styryl benzoxazole derivative [18F]-[2-[N-methyl-N-(2′-fluoroethyl)-4′-aminostyryl]benzoxazole] ([18F]-1) and its pre-clinical evaluation, including metabolic and biodistribution studies in male Wistar rats. The in vivo biological evaluation of [18F]-1 showed that this new radiotracer has a moderate brain uptake with a slow brain washout and a poor in vivo stability

The condensation of salicylaldehydes and malononitrile revisited : synthesis of new dimeric chromene derivatives

The reaction of salicylic aldehydes with malononitrile was reinvestigated, and the reaction pathway was followed by 1H NMR spectroscopy. A delicate control of the experimental conditions allowed the synthesis of 2-imino-2H-chromene-3-carbonitriles 1, (2-amino-3-cyano-4H-chromen-4-yl)malononitriles 2, 4-amino-5-imino-2,7-dimethoxy-5H-chromeno[3,4-c]pyridine-1-carbonitrile 12, and (4,5-diamino-1-cyano-1,10b-dihydro-2H-chromeno[3,4-c]pyridin-2-ylidene)malononitrile 13. Two novel 2-iminochromene dimers, with structures 8 and 9, were isolated and fully characterized. The activity of compound 8a on Aspergillus spp. growth and on ochratoxin A production was evaluated. The results of the bioassays indicate that compound 8a, applied at concentrations of 2 mM, totally inhibited the growth of the fungi tested. Ochratoxin A production by Aspergillus alliaceus was reduced by about 93% with a 200 μM solution of this compound. A moderate inhibitory effect was observed for the analogous structure 8b, and no inhibition was registered for compounds 2 and 1, used as synthetic precursors of the dimeric species 8

Contaminação fúngica das uvas e ocratoxina A em vinhos

[Extrato] Introdução Os fungos constituem um grande grupo de seres vivos ubíquos na Natureza. Estes microrganismos são em geral capazes de produzir uma grande variedade de metabolitos secundários, metabolitos estes que são considerados produtos naturais e, alguns, mesmo vitais para o fungo produtor (e.g., como seja a produção de melaninas que protegem contra a irradiação solar ou outros agentes agressores).[...]info:eu-repo/semantics/publishedVersio

Assessing the degradation of ochratoxin a using a bioassay : the case of contaminated winery wastewater

In vineyards the presence of certain fungi may lead to the production of the mycotoxin ochratoxin A (OTA) and subsequent contamination of grapes and wine. Furthermore, winery wastewaters contaminated with OTA may represent an environmental hazard. Therefore it is imperative to assess the fate of this mycotoxin in conventional wastewater treatment systems. The aim of the present work in this context is to assess the biological degradation of OTA. Experimental work was carried out in batch experiments with initial OTA to biomass concentration ratios (S0/X0) of 1.4 μg mg-1, 7.4 μg mg-1 and 11.9 μg mg-1. The assays were inoculated with activated sludge biomass unadapted to the substance under examination. The proposed bioassay demonstrates that OTA concentrations up to 100 μg L-1 can be degraded by microbial activity in activated sludge

Rhamnolipids inhibit aflatoxins production in Aspergillus flavus by causing structural damages in the fungal hyphae and down-regulating the expression of their biosynthetic genes

Aflatoxins are hepatotoxic and carcinogenic fungal secondary metabolites that usually contaminate crops and represent a serious health hazard for humans and animals worldwide. In this work, the effect of rhamnolipids (RLs) produced by Pseudomonas aeruginosa #112 on the growth and aflatoxins production by Aspergillus flavus MUM 17.14 was studied in vitro. At concentrations between 45 and 1500 mg/L, RLs reduced the mycelial growth of A. flavus by 2340% and the production of aflatoxins by 93.999.5%. Purified mono-RLs and di-RLs exhibited a similar inhibitory activity on fungal growth. However, the RL mixture had a stronger inhibitory effect on aflatoxins production at concentrations up to 190 mg/L, probably due to a synergistic effect resulting from the combination of both congeners. Using transmission electron microscopy, it was demonstrated that RLs damaged the cell wall and the cytoplasmic membrane of the fungus, leading to the loss of intracellular content. This disruptive phenomenon explains the growth inhibition observed. Furthermore, RLs down-regulated the expression of genes aflC, aflE, aflP and aflQ involved in the aflatoxins biosynthetic pathway (6.4, 44.3, 38.1 and 2.0-fold, respectively), which is in agreement with the almost complete inhibition of aflatoxins production. Overall, the results herein gathered demonstrate for the first time that RLs could be used against aflatoxigenic fungi to attenuate the production of aflatoxins, and unraveled some of their mechanisms of action.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER 000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy (HEMS), member of the PPBI (PPBI POCI-01-0145-FEDER-022122). A.I. Rodrigues and L. Abrunhosa acknowledge FCT for the grant SFRH/BD/111600/2015 and the Assistant Research contract CEECIND/00728/2017, respectively.info:eu-repo/semantics/publishedVersio

Evaluation of zearalenone in vitro removal by Saccharomyces cerevisiae strains isolated from bovine forage

Zearalenone (ZEN) is a mycotoxin that has relatively low acute toxicity. However, it is a potent oestrogen, interfering with the reproductive tract of animals. Among other effects, ZEN decreases animals fertility, and induces fibrosis in the uterus, breast cancer and endometrial carcinoma (Zinedine et al., 2007). Anti-mycotoxin additives (AMA) are defined as a group of products that, when added to animal feed, are capable of adsorbing, inactivating, or neutralizing mycotoxins in the gastrointestinal tract of animals. One example of these products are adsorbents based on yeast cell walls, a safe and beneficial animal feed additive (Abreu et al., 2008). When based on active cells, yeast based products also act as a probiotic, contributing to improve the general animal health because it stimulates their immune system and promotes the integrity of intestinal mucosa (Albino et al., 2006). Strains of Saccharomyces cerevisiae isolated from silage were tested for their ZEN removal capability. Their effect on - and b-zearalenol (-ZOL and b-ZOL) was also tested. Strains were grown on YPD separately supplemented with ZEN, -ZOL and b-ZOL, and their elimination from culture media was quantified over time by HPLC-FL.This study was carried out with grants from CYTED (Acción 109ac0371), CNPq, CAPES-DS and FAPUR/UFRRJ (Brazil). Luís Abrunhosa was supported by grant SFRH/BPD/43922/2008 from Fundação para a Ciência e Tecnologia – FCT, Portugal.. Authors also acknowledge the support of the Society for Applied Microbiology – SfAM

Callous-unemotional traits moderate anticipated guilt and wrongness judgments to everyday moral transgressions in adolescents

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyt.2021.625328/full#supplementary-materialCallous-unemotional (CU) traits observed during childhood and adolescence are thought to be precursors of psychopathic traits in adulthood. Adults with high levels of psychopathic traits typically present antisocial behavior. Such behavior can be indicative of atypical moral processing. Evidence suggests that moral dysfunction in these individuals may stem from a disruption of affective components of moral processing rather than from an inability to compute moral judgments per se. No study to date has tested if the dissociation between affective and cognitive dimensions of moral processing linked to psychopathic traits in adulthood is also linked to CU traits during development. Here, 47 typically developing adolescents with varying levels of CU traits completed a novel, animated cartoon task depicting everyday moral transgressions and indicated how they would feel in such situations and how morally wrong the situations were. Adolescents with higher CU traits reported reduced anticipated guilt and wrongness appraisals of the transgressions. However, our key finding was a significant interaction between CU traits and anticipated guilt in predicting wrongness judgments. The strength of the association between anticipated guilt and wrongness judgement was significantly weaker for those with higher levels of CU traits. This evidence extends our knowledge on the cognitive-affective processing deficits that may underlie moral dysfunction in youth who are at heightened risk for antisocial behavior and psychopathy in adulthood. Future longitudinal research is required to elucidate whether there is an increased dissociation between different components of moral processing from adolescence to adulthood for those with high psychopathic traits.This study was supported by the Portuguese Foundation for Science and Technology (FCT) research grant awarded to AS-C (PTDC/MHC-PCN/2296/2014), co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-016747). The study was conducted at the Psychology Research Center (PSI/01662), School of Psychology, University of Minho, supported by FCT through the Portuguese State Budget (Ref.: UIDB/PSI/01662/2020)

Validation study of the Narcissistic Personality Inventory-13 among a school sample of Portuguese youths

The main aim of the present study was to translate and validate the Narcissistic Personality Inventory-13 (NPI-13) among a school sample (N=543) of male and female Portuguese youths. The NPI-13 demonstrated good psychometric properties, namely in terms of its three-factor structure, internal consistency, convergent validity, discriminant validity and criterion-related validity. Positive correlations were found with Conduct Disorder symptoms, alcohol use, drug use and unprotected sex. The psychometric properties of the NPI-13 mostly justify its use among Portuguese adolescents in a school context