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Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked in vivo the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in Arabidopsis thaliana's root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in prophase in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.

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Introducción: Es importante la relación entre el desarrollo de las categorías originalidad, flexibilidad, autonomía y motivación del modo de actuación creativo. El objetivo del artículo consistió en elaborar un sistema de indicaciones para el desarrollo de categorías del modo de actuación creativo en estudiantes universitarios. Métodos: Se realizó una investigación mixta, donde el universo lo constituyeron estudiantes de la carrera de Pedagogía-Sicología de la Universidad de Sancti Spíritus "José Martí Pérez" en el curso 2021-2022 y se tomó una muestra aleatoria intencional de 24 educandos del tercer año. Resultados: El procesamiento estadístico de los instrumentos aplicados permitió ubicar al 75 % de la muestra entre un nivel medio y bajo en el desarrollo de categorías del modo de actuación creativo, por carencias en su expresión. Discusión: Desde fundamentos teóricos referenciados se analizó una propuesta de indicaciones que permiten la sistematización de contenidos de aprendizaje y facilitan el desarrollo de acciones autónomas y motivadoras para solucionar problemáticas en el contexto laboral. Conclusiones: La elaboración de indicaciones, desde la disciplina principal integradora y en estrecha relación con las categorías declaradas del modo de actuación creativo, facilitaron su desarrollo y demostraron pertinencia y factibilidad en el contexto de la práctica laboral.

Introduction: The relationship between the development of the categories of originality, flexibility, autonomy and motivation of the creative mode of action is important. The objective of the article was to develop a system of indications for the development of categories of the creative mode of action in university students. Methods: A mixed investigation was carried out, where the universe was made up of students of the Pedagogy-Psychology degree at the University of Sancti Spíritus "José Martí Pérez" in the 2021-2022 academic year and an intentional random sample of 24 students from the third year was taken. In the research, actions were designed to solve problems in work practice and a self-assessment scale about the development of the categories of the creative mode of action. Results: The statistical processing of the applied instruments allowed 75 % of the sample to be placed between a medium and low level in the development of categories of the creative mode of action, due to deficiencies in its expression. Discussion: From referenced theoretical foundations, a proposal of indications was analyzed that allow the systematization of learning content and facilitate the development of autonomous and motivating actions to solve problems in the work context. Conclusions: The development of indications, from the main integrative discipline and in close relationship with the declared categories of the creative mode of action, facilitated its development and demonstrated relevance and feasibility in the context of work practice.

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Accidental herbicide drift onto neighboring crops, such as soybeans, can seriously harm non-target plants, affecting their growth and productivity. This study examined the impact of simulated drift from ten different herbicides (2,4-D, dicamba, glyphosate, saflufenacil, oxyfluorfen, hexazinone, diuron, diquat, nicosulfuron, and isoxaflutole) on young soybean plants. These herbicides were applied at three simulated drift levels (1/4, 1/16, and 1/32) equivalent to recommended commercial doses, and the resulting symptoms were carefully evaluated. Simulated drift caused distinctive symptoms, including chlorosis, twisting, necrosis, and growth abnormalities, varying depending on each herbicide's mode of action. Dicamba proved more toxic than 2,4-D, and symptom severity increased with drift proportion, with all herbicides causing over 30% injury at the 1/16 proportion. Notably, 2,4-D, dicamba, glyphosate, hexazinone, and diquat exceeded the half-maximal inhibitory concentration (IC50) value, significantly reducing total biomass. Dicamba consistently caused 50% injury at all proportions, while hexazinone, at the highest dose proportion, led to plant mortality. Dicamba also had biomass accumulation beyond the growth reduction (GR50), whereas hexazinone exhibited less than 10% accumulation due to its capacity to induce plant mortality. This study emphasizes the importance of understanding herbicide drift effects on non-target crops for more effective and safe weed management strategies.

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Drosophila suzukii, an invasive insect pest, poses a significant threat to various fruit crops. The use of broad-spectrum insecticides to control this pest can reduce the effectiveness of biological control agents, such as the parasitoid Trichopria anastrephae. Here, we evaluated the toxicity of newly synthesized lactone derivatives on D. suzukii and their selectivity towards T. anastrephae. We used in silico approaches to identify potential targets from the most promising molecules in the D. suzukii nervous system and to understand potential differences in susceptibilities between D. suzukii and its parasitoid. Of the nine molecules tested, (rac)-8 and compound 4 demonstrated efficacy against the fly. Exposure to the estimated LC90 of (rac)-8 and compound 4 resulted in a mortality rate of less than 20% for T. anastrephae without impairing the parasitoid's functional parasitism. The in silico predictions suggest that (rac)-8 and compound 4 target gamma amino butyric acid (GABA) receptors and transient receptor potential (TRP) channels of D. suzukii. However, only the reduced interaction with TRP channels in T. anastrephae demonstrated a potential reason for the selectivity of these compounds on the parasitoid. Our findings suggest the potential for integrating (rac)-8 and compound 4 into D. suzukii management practices.

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Multidrug-resistant bacteria, such as ESBL producing-Klebsiella pneumoniae, have increased substantially, encouraging the development of complementary therapies such as photodynamic inactivation (PDI). PDI uses photosensitizer (PS) compounds that kill bacteria using light to produce reactive oxygen species. We test Ru-based PS to inhibit K. pneumoniae and advance in the characterization of the mode of action. The PDI activity of PSRu-L2, and PSRu-L3, was determined by serial micro dilutions exposing K. pneumoniae to 0.612 J/cm 2 of light dose. PS interaction with cefotaxime was determined on a collection of 118 clinical isolates of K. pneumoniae. To characterize the mode of action of PDI, the bacterial response to oxidative stress was measured by RT-qPCR. Also, the cytotoxicity on mammalian cells was assessed by trypan blue exclusion. Over clinical isolates, the compounds are bactericidal, at doses of 8 µg/mL PSRu-L2 and 4 µg/mL PSRu-L3, inhibit bacterial growth by 3 log10 (>99.9%) with a lethality of 30 min. A remarkable synergistic effect of the PSRu-L2 and PSRu-L3 compounds with cefotaxime increased the bactericidal effect in a subpopulation of 66 ESBL-clinical isolates to > 6 log10 with an FIC-value of 0.16 and 0.17, respectively. The bacterial transcription response suggests that the mode of action occurs through Type II oxidative stress. The upregulation of the extracytoplasmic virulence factors mrkD, magA, and rmpA accompanied this response. Also, the compounds show little or no toxicity in vitro on HEp-2 and HEK293T cells. Through the type II effect, PSs compounds are bactericidal, synergistic on K. pneumoniae, and have low cytotoxicity in mammals.

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PURPOSE: Acanthamoeba spp. are free-living amoebas with worldwide distribution and play an important role as disease-causing agents in humans. Drug inability to completely eradicate these parasites along with their toxic effects suggest urgent need for new antimicrobials. Nisin is a natural antimicrobial peptide produced by Lactococcus lactis. Nisin is also the only bacteriocin approved for use in food preservation. In this work, we analyzed the effect of nisin on the growth of Acanthamoeba castellanii trophozoites. METHODS: A total of 8 × 104 trophozoites were exposed to increasing concentrations of nisin to determine its activity. Changes in cell membrane and cellular cycle of trophozoites were investigated by flow cytometry, and nisin cytotoxicity in mammalian cells was evaluated in L929 cells by MTT method. RESULTS: After 24 h exposure to increasing nisin concentrations, an IC50 of 4493.2 IU mL-1 was obtained for A. castellanii trophozoites. However, after 72 h a recovery in amoebic growth was observed, and it was no longer possible to determine IC50. Flow cytometry analysis showed that nisin has no effect on the membrane integrity. Treatment with nisin induced cell-cycle arrest during G1 and S phases in A. castellanii trophozoites, which recovered their growth after 72 h. CONCLUSION: This is one of the first studies showing the effect of internationally approved nisin against A. castellanii trophozoites. Nisin caused cell-cycle arrest in trophozoites, momentarily interfering with the DNA replication process. The data highlight the amoebostatic activity of nisin, and suggest its use as an adjuvant for the treatment of infections caused by Acanthamoeba spp.

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Species of Burkholderia are highly versatile being found not only abundantly in soil, but also as plants and animals' commensals or pathogens. Their complex multireplicon genomes harbour an impressive number of polyketide synthase (PKS) and nonribosomal peptide-synthetase (NRPS) genes coding for the production of antimicrobial secondary metabolites (SMs), which have been successfully deciphered by genome-guided tools. Moreover, genome metrics supported the split of this genus into Burkholderia sensu stricto (s.s.) and five new other genera. Here, we show that the successful antimicrobial SMs producers belong to Burkholderia s.s. Additionally, we reviewed the occurrence, bioactivities, modes of action, structural, and biosynthetic information of thirty-eight Burkholderia antimicrobial SMs shedding light on their diversity, complexity, and uniqueness as well as the importance of genome-guided strategies to facilitate their discovery. Several Burkholderia NRPS and PKS display unusual features, which are reflected in their structural diversity, important bioactivities, and varied modes of action. Up to now, it is possible to observe a general tendency of Burkholderia SMs being more active against fungi. Although the modes of action and biosynthetic gene clusters of many SMs remain unknown, we highlight the potential of Burkholderia SMs as alternatives to fight against new diseases and antibiotic resistance.

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ABSTRACT Increasing antimicrobial resistance amongStaphylococcus aureusnecessitates a new antimicrobial with a different site of action. We have isolated a novel cyclic peptide-1 (ASP-1) fromBacillussubtiliswith potent activity against methicillin-resistantS. aureus(MRSA) at a minimum inhibitory concentration (MIC) of 8-64μg/ml. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of ASP-1 treated cells ofS. aureusATCC 29213 and an MRSA clinical isolate at MICs, with damages to the cell wall, membrane lysis and probable leakage of cytoplasmic contents at minimum bactericidal concentrations. The ultrastructure alterations induced by ASP-1 have also been compared with those of oxacillin-treated MRSA cells at its MIC using scanning electron microscopy.

RESUMEN El incremento de la resistencia antimicrobiana entre los tipos deS. aureusexige un nuevo agente antimicrobiano con un sitio de acción diferente. Aislamos un nuevo péptido cíclico (ASP-1) deBacillussubtiliscon potente actividad frente aS. aureusresistente a meticilina (SARM) en una concentración inhibitoria mínima (CIM) de 8-64μg/ml. Las micrografías obtenidas con microscopio electrónico de barrido mostraron cambios drásticos en la arquitectura celular de las células deS. aureusATCC 29213 tratadas con ASP-1, y un aislamiento clínico de SARM a la CIM, con daños a la pared celular, lisis de la membrana y probable fuga de contenido citoplasmático a concentraciones bactericidas mínimas. Comparamos también, las alteraciones de la ultraestructura inducidas por ASP-1 con las de células de SARM tratadas con oxacilina a su CIM, utilizando microscopio electrónico de barrido.

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A total of 12 compounds were synthesized from the natural sesquiterpene (-) drimenol (compounds 4 to 15). The synthesized compounds corresponded to N-phenyl-driman-9-carboxamide derivatives, similar to some fungicides that inhibit the electron-transport chain. Their structures were characterized and confirmed by 1H NMR, 13C NMR spectroscopy, and mass spectrometry. Compounds 5 to 15 corresponded to novel compounds. The effect of the compounds on the mycelial growth of Botrytis cinerea was evaluated. Methoxylated and chlorinated compounds in the aromatic ring (compounds 6, 7, 12, and 13) exhibited the highest antifungal activity with IC50 values between 0.20 and 0.26 mM. On the other hand, the effect on conidial germination of B. cinerea of one methoxylated compound (6) and one chlorinated compound (7) was analyzed, and no inhibition was observed. Additionally, compound 7 decreased 36% the rate of oxygen consumption by germinating conidia.

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The British Society for Parasitology (BSP) holds a biannual symposium devoted to the kinetoplastids, and seeks to cover the full gamut of research into these important organisms, and alternates with the Woods Hole Kinetoplastid Molecular Cell Biology meeting that serves a similar community. While normally embedded within the main BSP Spring meeting, on several occasions the symposium has enjoyed the opportunity of being hosted on mainland Europe. In 2020, the BSP was fortunate to spend some time in Granada in Spain, where a superb meeting with excellent science in a spectacular setting was overshadowed by news of an emerging novel coronavirus. In this editorial, we hope to have captured some of that excellent science and to highlight aspects of the many great papers and reviews in this special issue, as well as provide a few images from the meeting, which we hope for this who attended will bring back some fond memories.

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Introducción: El reciente perfeccionamiento curricular de la carrera de Medicina en la educación superior cubana suscita la búsqueda de alternativas científicas que contribuyan a la sistematización del proceso formativo de la atención médica integral en los servicios de la asistencia sanitaria esencial. Objetivo: Exponer una concepción teórico-metodológica para la formación del modo de actuación atención médica integral desde la disciplina Psicología. Métodos: El proceso investigativo asumió un enfoque metodológico mixto o multimodal, que siguió un diseño mixto explicativo secuencial, en el que se integraron métodos teóricos, empíricos, así como de análisis de la información y procesamiento de los datos. Este se desarrolló en la carrera de Medicina de la Universidad de Ciencias Médicas de Villa Clara entre septiembre de 2016 y enero de 2019, y abarcó los momentos de la exploración, el diseño y la evaluación del resultado científico propuesto. Resultados: Se pudo definir la connotación científica de la concepción teórico-metodológica propuesta, en respuesta a la estructura formal para la formación del modo de actuación atención médica integral y a la forma lógica de su vinculación con la disciplina Psicología. Conclusiones: Se estableció que una concepción teórico-metodológica para la formación del modo de actuación atención médica integral desde la disciplina Psicología debe integrar en su estructura los fundamentos generales que sustentan la lógica interna de esta, y los componentes teórico-conceptual y metodológico-instrumental que definen su organización e implementación práctica(AU)

Introduction: The recent curricular improvement of the medical major in Cuban higher education brings about the search for scientific alternatives that contribute to systematization of the training process for comprehensive medical care in essential healthcare services. Objective: To present a theoretical-methodological conception for the formation of a mode of action in comprehensive medical care from the psychology discipline. Methods: The research process followed a mixed or multimodal methodological approach, under a mixed sequential explanatory design, in which theoretical and empirical methods were integrated, as well as information analysis and data processing. This was developed, between September 2016 and January 2019, in the medical major of Villa Clara University of Medical Sciences, and covered the moments of exploration, design and assessment of the proposed scientific result. Results: It was possible to define the scientific connotation of the proposed theoretical-methodological conception, in response to the formal structure for the formation of a mode of action in comprehensive medical care and the logical way of its link with the psychology discipline. Conclusions: It was established that a theoretical-methodological conception for the formation of a mode of action in comprehensive medical care from the psychology discipline must integrate, into its structure, the general foundations that support its internal logic, as well as the theoretical-conceptual and methodological-instrumental components that define its organization and practical implementation(AU)

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Increasing antimicrobial resistance among Staphylococcus aureus necessitates a new antimicrobial with a different site of action. We have isolated a novel cyclic peptide-1 (ASP-1) from Bacillussubtilis with potent activity against methicillin-resistant S. aureus (MRSA) at a minimum inhibitory concentration (MIC) of 8-64µg/ml. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of ASP-1 treated cells of S. aureus ATCC 29213 and an MRSA clinical isolate at MICs, with damages to the cell wall, membrane lysis and probable leakage of cytoplasmic contents at minimum bactericidal concentrations. The ultrastructure alterations induced by ASP-1 have also been compared with those of oxacillin-treated MRSA cells at its MIC using scanning electron microscopy.

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Bacillus thuringiensis is a potential control agent for plant-parasitic nematodes. Nematode intestinal receptors for Cry21-type toxins are poorly known. Therefore, a strategy was tested as a primary screening tool to find possible Cry toxin receptors, using a nematicidal Bt strain and the RNAi technique on Caenorhabditis elegans. Six genes encoding intestinal membrane proteins were selected (abt-4, bre-1, bre-2, bre-3, asps-1, abl-1) as possible targets for Cry proteins. Fractions of each selected gene were amplified by PCR. Amplicons were cloned into the L4440 vector to transform the E. coli HT155 (DE3) strain. Transformed bacteria were used to silence the selected genes using the RNAi feeding method. Nematodes with silenced genes were tested with the Bt strain LBIT-107, which harbors the nematicidal protein Cry21Aa3, among others. Results indicated that nematodes with the silenced abt-4 gene were 69.5% more resistant to the LBIT-107 strain, in general, and 79% to the Cry21Aa3 toxin, specifically.

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RESUMEN Fundamento: La práctica de la educación intercultural en Cuba es un campo disciplinar que demanda mayor preparación en el modo de actuación profesional de los docentes universitarios. Objetivo: Construir un programa de preparación, centrado en la solución de conflictos, para perfeccionar el modo de actuación profesional de los docentes universitarios para la educación intercultural. Metodología: Se realizó una investigación en la Universidad de Sancti Spíritus José Martí Pérez, en la que se utilizó la metodología cualitativa basada en el estudio de caso del modo de actuación profesional de los docentes para la educación intercultural. Resultados: El diagnóstico pedagógico integral no se tuvo en cuenta para la identificación y solución de los conflictos interculturales, dependiendo del estatus de igualdad grupal alcanzado. La preparación en educación intercultural, centrada en la solución de conflictos, demostró la efectividad de trabajar en correspondencia al sistema de acciones propias de la dirección del proceso pedagógico. Conclusiones: El programa de preparación permitió reconocer la validez de la experiencia pedagógica practicada, así como la pertinencia de otras perspectivas foráneas compatibles y el manejo conceptual de los principios y competencias para la educación intercultural.

ABSTRACT Background: The practice of intercultural education in Cuba is a disciplinary field that requires greater preparation in the professional way of acting of university teachers. Objective: To build a preparation program, focused on conflicts resolution, to improve the professional performance of university teachers for intercultural education. Methodology: An investigation was carried out at the University of Sancti Spíritus José Martí Pérez, using the qualitative methodology based on the case study of the professional performance of teachers for intercultural education. Results: The comprehensive pedagogical diagnosis was not taken into account for the identification and solution of intercultural conflicts, depending on the group equality status achieved. The preparation in intercultural education, focused on conflict resolution, demonstrated the effectiveness of working in correspondence with the system of actions proper to the direction of the pedagogical process. Conclusions: The preparation program allowed to recognize the validity of the pedagogical experience practiced, as well as the relevance of other compatible foreign perspectives and the conceptual handling of the principles and competences for intercultural education.

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RESUMEN Fundamento: La práctica de la educación intercultural en Cuba es un campo disciplinar que demanda mayor preparación en el modo de actuación profesional de los docentes universitarios. Objetivo: Construir un programa de preparación, centrado en la solución de conflictos, para perfeccionar el modo de actuación profesional de los docentes universitarios para la educación intercultural. Metodología: Se realizó una investigación en la Universidad de Sancti Spíritus José Martí Pérez, en la que se utilizó la metodología cualitativa basada en el estudio de caso del modo de actuación profesional de los docentes para la educación intercultural. Resultados: El diagnóstico pedagógico integral no se tuvo en cuenta para la identificación y solución de los conflictos interculturales, dependiendo del estatus de igualdad grupal alcanzado. La preparación en educación intercultural, centrada en la solución de conflictos, demostró la efectividad de trabajar en correspondencia al sistema de acciones propias de la dirección del proceso pedagógico. Conclusiones: El programa de preparación permitió reconocer la validez de la experiencia pedagógica practicada, así como la pertinencia de otras perspectivas foráneas compatibles y el manejo conceptual de los principios y competencias para la educación intercultural.

ABSTRACT Background: The practice of intercultural education in Cuba is a disciplinary field that requires greater preparation in the professional way of acting of university teachers. Objective: To build a preparation program, focused on conflicts resolution, to improve the professional performance of university teachers for intercultural education. Methodology: An investigation was carried out at the University of Sancti Spíritus José Martí Pérez, using the qualitative methodology based on the case study of the professional performance of teachers for intercultural education. Results: The comprehensive pedagogical diagnosis was not taken into account for the identification and solution of intercultural conflicts, depending on the group equality status achieved. The preparation in intercultural education, focused on conflict resolution, demonstrated the effectiveness of working in correspondence with the system of actions proper to the direction of the pedagogical process. Conclusions: The preparation program allowed to recognize the validity of the pedagogical experience practiced, as well as the relevance of other compatible foreign perspectives and the conceptual handling of the principles and competences for intercultural education.

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Although development of antimicrobial resistance by bacteria is a natural phenomenon, the antibiotic resistance crisis is a reality that leads us in a gap of antimicrobial alternatives on therapeutics. Considering this cruel reality and committed to contribute to look for new antibacterial agents, this manuscript presents a review of easy laboratory methods that evaluate the mode of action of compounds, since it is a basic requirement for the discovery and development of new drugs. The literature was screened by searching the keywords "mode of action", "antibiotic", "antimicrobial activity", "inhibition mode", "method" and "bacteria" in Pubmed, Scopus, Science Direct and BVS in a period of time from 2000 to 2019. This review demonstrates the wide variety of methods that can be employed in research on mechanisms of action of antibacterial substances. Therefore, we compiled different protocols (presented in the supplementary material), available in the literature, with the purpose of facilitating the start of experiments.

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Aedes aegypti is the vector of important diseases like dengue, zika, chikungunya, and yellow fever. Vector control is pivotal in combating the spread of these mosquito-borne illnesses. Photoactivable larvicide curcumin obtained from Curcuma longa Linnaeus has shown high potential for Ae. aegypti larvae control. However, the toxicity of this photosensitizer (PS) might jeopardize non-target aquatic organisms. The aim of this study was to evaluate the toxicity of this PS to Daphnia magna and Danio rerio, besides assessing its mode of action through larvae biochemical and histological studies. Three PS formulations were tested: PS in ethanol+DMSO, PS in sucrose, and PS in D-mannitol. The LC50 of PS in ethanol+DMSO to D. rerio was 5.9 mg L-1, while in D. magna the solvents were extremely toxic, and LC50 was not estimated. The PS formulations in sugars were not toxic to neither of the organisms. Reactive oxygen species (ROS) were generated in D. magna exposed to 50 mg L-1 of PS in D-mannitol, and D. rerio did not elicit this kind of response. D. magna feeding rates were not affected by the PS in D-mannitol. Concerning Ae. aegypti larvae, there were changes in reduced glutathione and protein levels, while catalase activity remained stable after exposure to PS in D-mannitol and sunlight. Histological changes were observed in larvae exposed to PS in sucrose and D-mannitol, most of them irreversible and deleterious. Our results show the feasibility of this photolarvicide use in Ae. aegypti larvae control and its safety to non-target organisms. These data are crucial to this original vector control approach implementation in public health policies.

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ABSTRACT Leaf-cutting ants are controlled with toxic baits. For the method's greater efficiency, the baits must be distributed and processed by workers during fungus cultivation. To test hypotheses whether the mode of action of the active ingredients, which blocks the sodium channels and interrupts the production of ATP in the mitochondria, interferes with fragment distribution in nests; the dispersion of pellets fragments during fungus cultivation by workers was assessed, spatially referencing the fragment onto the fungus garden. Pellets fragments were randomly distributed, but the amount pellets fragments was influenced by the way that the active ingredient acts in the colony.

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Chagas disease, caused by the flagellate parasite Trypanosoma cruzi, is a wellknown neglected tropical disease. This parasitic illness affects 6-7 million people and can lead to severe myocarditis and/or complications of the digestive tract. The changes in its epidemiology facilitate co-infection with the Human Immunodeficiency Virus (HIV), making even more difficult the diagnosis and prognosis. The parasitic infection is reactivated in T. cruzi/HIV co-infection, with the appearance of unusual manifestations in the chronic phase and the exacerbation of classical clinical signs. The therapeutic arsenal to treat Chagas disease, in all its clinical forms, is restricted basically to two drugs, benznidazole and nifurtimox. Both drugs are extremely toxic and the therapeutic efficacy is still unclear, making the clinical treatment a huge issue to be solved. Therefore, it seems obvious the necessity of new tangible approaches to combat this illness. In this sense, the repositioning of approved drugs appears as an interesting and viable strategy. The discovery of Human Immunodeficiency Virus Aspartyl Peptidase Inhibitors (HIV-PIs) represented a milestone in the treatment of Acquired Immune Deficiency Syndrome (AIDS) and, concomitantly, a marked reduction in both the incidence and prevalence of important bacterial, fungal and parasitic co-infections was clearly observed. Taking all these findings into consideration, the present review summarizes the promising and beneficial data concerning the effects of HIV-PIs on all the evolutionary forms of T. cruzi and in important steps of the parasite's life cycle, which highlight their possible application as alternative drugs to treat Chagas disease.

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