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Background: Piotr Ya. Galperin and his collaborator Nina F. Talyzina performed solid experimental work which led them to propose the theory of stage-by-stage formation of mental actions and concepts, as well as a method to investigate cognitive processes, whose conceptual and procedural streamlining demands analysis and systematization., Objective: To investigate the formative experiment of P.Ya. Galperin and N.F. Talyzina, with the aim of analyzing their contributions to the method of psychological investigation of cognitive processes., Design: The article is part of a theoretical research project on developmental didactics systems, of which the Galperin-Talyzina system is one. Russian works by the two authors and their translations into English, Spanish, and Portuguese, as well as works by other psychologists and educators from the Galperin-Talyzina school, were sources of the work., Results: The experiments of P.Ya. Galperin and N.F. Talyzina studied, promoted, and analyzed the assimilation of new knowledge and mental actions, by introducing different conditions. The article systematizes the stages and procedures of such experiments, as well as the series and steps of diagnosis of the developmental level and the formation of mental actions and concepts, in relation to the type of Orienting Basis of an Action (OBA)., Conclusion: The theory was built on the basis of simultaneous production of a method to study the genesis of the cognitive processes and the theory of stage-by-stage formation of mental actions and concepts; it led us to define the method of P.Ya. Galperin and N.F. Talyzina as a gradual formation experiment., Competing Interests: The authors declare no conflict of interest., (© Lomonosov Moscow State University, 2023© Russian Psychological Society, 2023.)

Mancozeb (MZ) is a broad-spectrum fungicide used worldwide in several crops. Neurological disorders in humans and animals have been associated with exposure to this compound by mechanisms still not fully understood. Drosophila melanogaster represents a reliable model in toxicological studies, presenting genetic and biochemical similarities with mammals. In this study, D. melanogaster flies were exposed for 15 days to MZ through the food (5 and 10 mg/mL). After that period, the efficiency of mitochondrial respiration complexes and metabolic markers were analyzed and evaluated. Flies presented weight loss, lower glucose, trehalose, and glycogen levels, and augmented levels of triglycerides concerning control (non-treated group). Acetyl-CoA Synthetase (ACeCS-1) and Acyl-Coenzyme Synthetase (ACSL1) contents were unchanged by MZ treatment. Mitochondrial respiration of flies was targeted by MZ treatment, evidenced by a decrease in oxygen consumption and bioenergetics rate and inhibition in mitochondrial complexes I/II. These results suppose that an impairment in mitochondrial respiration jointly with reduced levels of energetic substrates might be a mechanism involved in MZ deleterious effects, possibly by the limitation of ATP's availability, necessary for essential cellular processes., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Fungal volatile organic compounds (VOCs) comprise a group of compounds commonly found in damp or water-damaged indoor places affecting air quality. Indoor fungal pollution is a severe threat to human health, contributing to the onset of allergic diseases. The compound 1-octen-3-ol, known as "mushroom alcohol", is the most abundant VOC and confers the characteristic mold odor. Exposure to 1-octen-3-ol induces inflammatory markers and episodes of allergic rhinitis and conjunctivitis; however, the effects of this compound towards mitochondria are fairly known. The present study aimed to evaluate the effects of 1-octen-3-ol on inflammatory targets and on mitochondrial morphology and bioenergetic rate in D. melanogaster. Drosophilas were exposed by inhalation to 2.5 μL/L and 5 μL/L of 1-octen-3-ol for 24 h. Observation showed a decreasing in the survival and locomotor ability of flies. Superoxide dismutase (SOD) activity was induced whereas Catalase (CAT) activity was inhibited. Analysis of the mitochondria respiration, detected inhibition of complex I and II in the electron transport chain and a decreased bioenergetic rate. Electronic microscopy provided morphological insights of the mitochondrial status in which a disarrangement in mitochondrial cristae profile was observed. 1-Octen-3-ol induced increased activity of caspase 3/7 and ERK phosphorylation. The mRNA relative steady-state levels of p38 MAPK and JNK were down-regulated, whereas NF-κB and p53 were up-regulated. In parallel, nitrite levels were induced in relation to the non-exposed group. These findings point to the mitochondria as a crucial target for the toxicity of 1-octen-3-ol in parallel with activation of pro-inflammatory factors and apoptotic signaling pathway cascade., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Croton campestris A. St-Hill popularly known as "velame do campo" is a native species of the savannah from northeastern Brazil, being used in folk medicine due to its beneficial effects in the treatment of many diseases, inflammation, detoxification, gastritis, and syphilis; however, its potential use as an antidote against organophosphorus compound poisoning has not yet been shown. Here, the protective effect of the methanolic fraction of C. campestris A. St.-Hill (MFCC) in Drosophila melanogaster exposed to chlorpyrifos (CP) was investigated. Flies were exposed to CP and MFCC during 48 h through the diet. Following the treatments, parameters such as mortality, locomotor behavior, and oxidative stress markers were evaluated. Exposure of flies to CP induced significant impairments in survival and locomotor performance. In parallel, increased reactive oxygen species and lipoperoxidation occurred. In addition, the activity of acetylcholinesterase was inhibited by CP, and superoxide dismutase and glutathione S-transferase activity was induced. Treatment with MFCC resulted in a blockage of all CP-induced effects, with the exception of glutathione S-transferase. Among the major compounds found in MFCC, only gallic acid (GA) showed a protective role against CP while quercetin and caffeic acid alone were ineffective. When in combination, these compounds avoided the toxicity of CP at the same level as GA. As far as we know, this is the first study reporting the protective effect of MFCC against organophosphate toxicity in vivo and highlights the biotechnological potential of this fraction attributing a major role in mediating the observed effects to GA. Therefore, MFCC may be considered a promising source for the development of new therapeutic agents for the treatment of organophosphate intoxications., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 Karen Kich Gomes et al.)

Permethrin (PM) is a synthetic pyrethroid insecticide widely used as domestic repellent. Damage effects to nontarget organisms have been reported, particularly in the early stages of development. Studies indicate redox unbalance as secondary PM effect. Therefore, our goal was to investigate the acute PM effects on larval zebrafish. Larvae (6 days postfertilization) were exposed to PM (25-600 μ g/L) during 24 hours, and 50% lethal concentration was estimated. For subsequent assays, the sublethal PM concentrations of 25 and 50 μ g/L were used. PM increased anxiety-like behaviors according to the Novel Tank and Light-Dark tests. At the molecular level, PM induced increased ROS, which may be related to the increased lipid peroxidation, DNA damage, and apoptosis detected in PM-exposed organisms. In parallel, upregulation of the antioxidant system was detected after PM exposure, with increased superoxide dismutase, glutathione S-transferase and glutathione reductase activities, and thiol levels. The increased of Nrf2 target genes and the activation of an electrophile response element-driven reporter Tg( EPRE :LUC-EGFP) suggest that the Nrf2 pathway can mediate a fast response to PM, leading to antioxidant amplification. By using high-resolution respirometry, we found that exposure to PM decreased the oxygen consumption in all respiratory stages, disrupting the oxidative phosphorylation and inhibiting the electron transfer system, leading to decrease in bioenergetics capacity. In addition, PM led to increases of residual oxygen consumption and changes in substrate control ratio. Glucose metabolism seems to be affected by PM, with increased lactate dehydrogenase and decreased citrate synthase activities. Taken together, our results demonstrated the adverse effects of acute sublethal PM concentrations during larval development in zebrafish, causing apparent mitochondrial dysfunction, indicating a potential mechanism to redox unbalance and oxidative stress, which may be linked to the detected cell death and alterations in normal behavior patterns caused by acute PM exposure., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Mauro Eugênio Medina Nunes et al.)

Parkinson's disease is a degenerative and progressive illness characterized by the degeneration of dopaminergic neurons. 6-hydroxydopamine (6-OHDA) is a widespread model for induction of molecular and behavioral alterations similar to Parkinson and has contributed for testing of compounds with neuroprotective potential. The Brazilian plant Anacardium microcarpum is used in folk medicine for treatment of several illnesses; however, the knowledge about toxicology and biological effects for this plant is very rare. The neuroprotective effect from hydroalcoholic extract and methanolic and acetate fraction of A. microcarpum on 6-OHDA-induced damage on chicken brain slices was investigated in this study. 6-OHDA decreased cellular viability measured by MTT reduction assay, induced lipid peroxidation by HPLC, stimulated Glutathione-S-Transferase and Thioredoxin Reductase activity, and decreased Glutathione Peroxidase activity and the total content of thiols containing compounds. The methanolic fraction of A. microcarpum presented the better neuroprotective effects in 6-OHDA-induced damage in relation with hydroalcoholic and acetate fraction. The presence of AKT and ERK1/2 pharmacological inhibitors blocked the protective effect of methanolic fraction suggesting the involvement of survival pathways in the neuroprotection by the plant. The plant did not prevent 6-OHDA autoxidation or 6-OHDA-induced mitochondrial dysfunction. Thus, the neuroprotective effect of the methanolic fraction of A. microcarpum appears to be attributed in part to chelating properties of extract toward reactive species and is dependent on ERK1/2 and AKT phosphorylation. This study contributes to the understanding of biochemical mechanisms implied in neuroprotective effects of the vegetal species A. microcarpum.

We conducted an investigation to evaluate the effects of Brazilian Pampa biome honey and its major phenolic compounds on the development of an erected wings posture phenotype and related mitochondrial aspects induced by Hypoxia/Reoxygenation (H/R) in Drosophila melanogaster. Flies were pre-treated for 3 days with a 10% honey solution and different concentrations of caffeic acid and ρ-coumaric acid and then submitted to hypoxia for 3 h. We observed that after reoxygenation, some flies acquired an erected wings posture and that this feature may be related to mortality. In addition, H/R induced down-regulation of ewg mRNA expression, which could be associated to the observed complex phenotype. H/R also caused a dysregulation in opa1-like, ldh and diap genes expression and reduced O 2 fluxes in flie's mitochondria. Honey mitigated opa1-like mRNA expression changes provoked by H/R. Differently from honey, caffeic and ρ-coumaric acids displayed no protective effects. In conclusion, we report for the first time the protective effects of honey against complex phenotypes and mitochondrial changes induced by H/R in adult flies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Mancozeb (MZ), a manganese- and zinc-containing ethylene-bis-dithiocarbamate, is a broad-spectrum fungicide. Harmful effects of this fungicide have been reported in nontarget organisms via a not fully understood mechanism. Drosophila melanogaster has provided remarkable contributions for toxicological studies. This work was aimed at evaluating the biochemical targets and implication of oxidative stress in MZ-mediated toxicity in drosophilas. Exposure of flies for fifteen days to MZ at 5 and 10 mg/mL through the diet impaired locomotor performance and induced fly mortality. In parallel, it caused lipid peroxidation and reactive oxygen species (ROS) formation and Mn overload. MZ inhibited superoxide dismutase and inducted catalase and glutathione S-transferase activities. Nitric oxide and reduced glutathione levels were significantly decreased by MZ. Heat shock proteins (HSP70 and HSP83) and Nrf2 mRNA levels were significantly augmented in MZ-exposed flies. Our study reinforced the use of Drosophila melanogaster as a reliable model for the study of biochemical targets of pesticides, and based on our data, MZ induced oxidative damage and Mn accumulation in a concentration-dependent manner. An adaptative cellular state was inducted by the lower concentration of pesticide, possibly contributing to the slighter damage observed.

Anacardium microcarpum Ducke (Anacardiaceae) is a native species of Brazil used in folk medicine for the treatment of several illnesses although its antioxidant activity has been reported in vitro , there is no evidence of this effect in an in vivo model. Here, we investigated the potential protective effect of hydroalcoholic extract (AMHE), methanol (AMMF) and acetate (AMAF) fraction of A. microcarpum against paraquat toxicity on survivorship, locomotor performance, antioxidant enzymes activity and reactive species using Drosophila melanogaster . Flies were exposed to the extract or fractions (1 and 10 mg/ml) in the presence or absence of paraquat (5 mM) in sucrose solution for 72 h. In addition, total phenolic content of extract and fractions was evaluated as well as ABTS radical scavenging capacity. Our results demonstrated that AMAF presented higher content of phenols and ABTS chelating potential. Treatment of flies with the extract or fractions did not alter the survivorship, locomotor ability, and acetylcholinesterase (AchE) activity per se. Paraquat caused 85 % mortality of flies and 30 % increase in reactive species generation, which were significantly attenuated by AMHE and AMMF. AAMF increased catalase activity (from 66.77 ± 6.64 to 223.94 ± 25.92 mU/mg of protein), while AMAF increased GST activity (from 477.76 ± 92 to 770.19 ± 147.92 mU/mg of protein) and catalase activity (from 66.77 ± 6.64 to 220.54 ± 26.63 mU/mg of protein). AMHE and AMMF were more effective in protecting against paraquat toxicity. Taken together, the data indicate the potential of this plant in acting as a protective and antioxidant agent in vivo .

Exposure to organophosphate compounds, such as chlorpyrifos, has been linked to disturbances on cell signaling pathways. Mitogen activated protein kinases (MAPK) are a family of protein kinases involved in a range of cellular processes, including stress response, apoptosis and survival. Therefore, changes in the activation state of these kinases may characterize key mechanisms of toxicity elicited by xenobiotics. Here we report data on the phosphorylation of p38MAPK and JNK, members of the MAPK family, in Drosophila melanogaster exposed to chlorpyrifos, as characterized by western blotting assays.