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Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries, reduces neuroinflammation by driving macrophages toward an antiinflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animal models. Improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred independently from alterations in microglia function and inflammation. We found, mechanistically, that phloretin acts as a direct ligand for the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma, thereby promoting the maturation of OPCs. Together, our findings indicate that phloretin has proregenerative properties in central nervous system disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions aimed at promoting remyelination.
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Células Precursoras de Oligodendrócitos , Remielinização , Animais , Camundongos , Remielinização/fisiologia , Floretina/farmacologia , Camundongos Endogâmicos C57BL , Oligodendroglia , Diferenciação Celular/fisiologia , Bainha de MielinaRESUMO
BACKGROUND: Macrophages play a dual role in neuroinflammatory disorders such as multiple sclerosis (MS). They are involved in lesion onset and progression but can also promote the resolution of inflammation and repair of damaged tissue. In this study, we investigate if and how phloretin, a flavonoid abundantly present in apples and strawberries, lowers the inflammatory phenotype of macrophages and suppresses neuroinflammation. METHODS: Transcriptional changes in mouse bone marrow-derived macrophages upon phloretin exposure were assessed by bulk RNA sequencing. Underlying pathways related to inflammation, oxidative stress response and autophagy were validated by quantitative PCR, fluorescent and absorbance assays, nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice, western blot, and immunofluorescence. The experimental autoimmune encephalomyelitis (EAE) model was used to study the impact of phloretin on neuroinflammation in vivo and confirm underlying mechanisms. RESULTS: We show that phloretin reduces the inflammatory phenotype of macrophages and markedly suppresses neuroinflammation in EAE. Phloretin mediates its effect by activating the Nrf2 signaling pathway. Nrf2 activation was attributed to 5' AMP-activated protein kinase (AMPK)-dependent activation of autophagy and subsequent kelch-like ECH-associated protein 1 (Keap1) degradation. CONCLUSIONS: This study opens future perspectives for phloretin as a therapeutic strategy for neuroinflammatory disorders such as MS. TRIAL REGISTRATION: Not applicable.
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Autofagia/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Macrófagos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Floretina/farmacologia , Animais , Autofagia/fisiologia , Células Cultivadas , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/deficiência , Floretina/uso terapêuticoRESUMO
The invasion of Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) worldwide has disrupted existing or developing integrated pest management (IPM) programs in soft-skinned fruits. Currently, with a reliance on only broad-spectrum insecticides, there is a critical call for alternative control measures. Behavioural control is one of the pillars of IPM, and, in the present study, it is investigated whether mass trapping could be viable for D. suzukii management. By quantifying trap interference in 4 × 4 replicate trapping grids, an estimate of the attraction radius for a certain attractant and context can be obtained. Traps designed for dry trapping (no drowning solution, but a killing agent inside) and synthetic controlled released experimental lures were tested in a two-year field study. Apple cider vinegar (ACV) was included as a reference bait and trials were performed with 5, 10 and 15 m inter-trap spacings at different seasonal timings. Clear trap interference and, hence, overlapping attraction radii were observed both in spring and summer for both the synthetic lures and ACV. In early spring, ACV shows the most potential for mass trapping, however from June onwards, the experimental dry lures show equal or better results than ACV. Based on our findings, workable trap densities are deemed possible, encouraging further development of mass trapping strategies for the control of D. suzukii.
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The woolly apple aphid Eriosoma lanigerum (Homoptera: Aphidiae) is an important pest in apple orchards worldwide. Since the withdrawal or restricted use of certain broad-spectrum insecticides, E. lanigerum has become one of the most severe pests in apple growing areas across Western Europe. At present, effective limitation of woolly aphid populations relies on a good synergy between chemical control treatments and biological suppression by beneficial arthropods, especially by its main specific natural enemy, the parasitoid Aphelinus mali (Hymenoptera: Aphelinidae). To develop a knowledge-based decision support system, detailed monitoring data of both species were collected in the field (region of Sint-Truiden, Belgium) for a period of ten years (2010-2020). Aphelinus mali flights were monitored in the field, starting before flowering until the end of the second-generation flight at minimum. The seasonal occurrence of the most important management stages of E. lanigerum, e.g., start of wool production or activity on aerial parts in spring and migration of crawlers from colonies towards flower clusters or shoots, were thoroughly monitored. All obtained data were compared with historical and literature data and analysed in a population dynamics phenological model. Our outcomes showed that the emergence of first-generation A. mali adults (critical for the first parasitation activity and the basis for following A. mali generations in the continuation of the season) can be accurately predicted by the developed model. Hence, this information can be utilized to avoid insecticide sprayings with detrimental side effects at this particular moment as demonstrated by the outcomes of a field trial. In addition, the start of migration of E. lanigerum crawlers towards flower clusters or shoots is accurately predicted by the model. In conclusion, our results demonstrate that the model can be used as decision support system for the optimal timing of control treatments in order to achieve effective control of E. lanigerum with maximal biological suppression by its main natural enemy.
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The spotted wing drosophila, Drosophila suzukii, is an invasive pest species from Southeast Asia that was recently introduced in Europe and North America. As this fruit fly lays its eggs in ripening soft-skinned fruit, it causes great damage to a variety of crops, including cherries, blueberries, blackberries, raspberries, grapes, plums and strawberries. Consequently, there is a great demand for an effective and species-specific lure, which requires the development of successful attractants. Until now, there is no lure available that is species-specific and can detect the presence of D. suzukii before infestation. As blackberry (Rubus fruticosus) is one of the preferred host crops of D. suzukii, the volatile compounds of R. fruticosus berries are here identified and quantified using multiple headspace SPME (solid phase micro extraction) GC-MS (gas chromatography-mass spectrometry). Subsequently, the attractivity of 33 of the identified compounds was tested with a two-choice laboratory bioassay. Acetaldehyde, hexyl acetate, linalool, myrtenol, L-limonene and camphene came out as significantly attractive to D. suzukii. The first four attractive compounds induced the strongest effect and therefore provided the best prospects to be implemented in a potential lure. These findings could contribute towards the development of more effective attractants for monitoring and mass trapping D. suzukii.
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Recently, the concept of Integrated Pest Management (IPM) was further extended into Integrated Pest and Pollinator Management (IPPM). Implementation of IPPM strategies entails the combination of actions for pest and pollinator management providing complementary or synergistic benefits for yield and/or quality of the harvest. The aim of this study was to examine IPPM elements (i.e., mixed hedgerow, nesting boxes for mason bees, Osmia spp.) and demonstrate their impact in the practical context of modern commercial fruit cultivation in a 4-year case study in an intensive 'Conference' pear orchard. The outcomes of visual observations during transect walks and molecular analysis of pollen collected by mason bees, showed the importance of additional floral resources for the presence of mason bees and other pollinating insects in the orchard environment. Pear quality assessments indicated that insect-mediated pollination had a significant positive impact, with a tendency for higher quality pears in the close vicinity of Osmia nesting boxes. However, despite the fact that pear pollen was also detected in Osmia spp. nest cells, the amount and frequency of pear pollen collection for their nest built-up turned out to be rather low. In the same intensive pear orchard studied for pollination effects, we simultaneously demonstrate the impact of a mixed hedgerow to enhance integrated pest control.
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Feeding a rising population of currently 7.8 billion people globally requires efficient agriculture, which is preferably sustainable. Today, farmers are largely dependent on synthetic fungicides to avoid food losses caused by fungal diseases. However, the extensive use of these has resulted in the emergence of fungicide-resistant pathogens and concerns have been raised over the residual effects on the environment and human health. In this regard, biocontrol agents (BCAs) have been proposed as an alternative to standard fungicides but their disease management capacity is usually incomplete and heavily relies on uncontrollable environmental conditions. An integrated approach combining BCAs with fungicides, which is the focus of this review, is put forward as a way to reduce the fungicide doses to manage plant diseases and thereby their residue on harvested crops. In addition, such a strategy of combining antifungal treatments with different modes of action reduces the selection pressure on pathogens and thereby the chances of resistance development. However, to allow its large-scale implementation, further knowledge is needed, comprising timing, number and interval of repeated BCA applications and their compatibility with fungicides. The compatibility of BCAs with fungicides might differ when applied in a mixture or when used in alternation.
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The marking of Drosophila suzukii can be an important instrument for studying the ecology and behaviour of this economically important fruit pest, aiding the development of new Integrated Pest Management (IPM) tools or strategies. There is, however, a need for a cost-effective methodology that provides an easily detectable and stable mark. Whereas fluorescent pigment powders are often used in entomological research, the pigments (series, dyes), application techniques, or doses need to be evaluated for each studied species in terms of their efficacy and possible adverse effects on the performance of the insect. The effectiveness of different application techniques and dyes (RadGlo® TP-series) and their effect on the survival of adult D. suzukii were investigated in the laboratory. Furthermore, the influence of the marking on the behaviour of the flies was examined in laboratory trap assays (olfaction) and a field recapture study (general orientation). The persistence and detectability of the marks was evaluated both on living flies (for different application techniques) and dead flies under trapping/storage conditions. The use of fluorescent powders to mark D. suzukii flies yielded a clearly detectable and highly persistent mark, without any adverse effects on the survival and behaviour of the flies.
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BACKGROUND: Spotted wing drosophila (SWD), Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), is a pest of stone and small fruits causing considerable economic losses. Current management strategies rely primarily on calendar-based spraying, owing to the poor relationship between monitoring data and damage levels, and the lack of success of mass-trapping tools. The aim of this study was to evaluate different trap models for SWD, with an emphasis on their fly-retention capacity. To this end, we examined and quantified the added value of two fly-retaining trap features; tunnel entries to impede escape and an insecticide-coated inner surface as a killing agent. RESULTS: An insecticide-coated inner surface resulted in significantly higher trap retention after 24 h in the laboratory (4.9- to 7.4-fold greater, depending on trap type) compared to a noncoated trap. Trapping efficacy was significantly improved in field trials by such a killing agent in the trap (1.2- to 4.5-fold greater). Tunnel entries significantly improved trap retention in the laboratory and field (by 1.5-fold). CONCLUSION: The outcomes of this study clearly reveal the substantial impact of the fly-retention capacity of SWD traps on their overall capture performances. It was demonstrated for the first time that an insecticide-coated inner surface as a killing agent significantly improves trap efficacy for SWD. This finding can readily be implemented in any trap model to improve monitoring and mass trapping of SWD. Also tunnel entries were shown to have a significant influence on the fly retention and, hence, substantially enhance trapping efficacy.
Assuntos
Drosophila , Animais , Frutas , Controle de Insetos , Inseticidas , Fosfatase Ácida Resistente a TartaratoRESUMO
Worldwide monitoring programs of the invasive fruit pest Drosophila suzukii Matsumura (Diptera: Drosophilidae), using fermentation baits like apple cider vinegar (ACV), revealed a counterintuitive period of low trap catches during summer, followed by an autumn peak. In this study, we demonstrate that ACV baited traps indeed provide a distorted image of the D. suzukii population dynamics as it is possible to capture higher numbers during this "low capture period" with synthetic lures. It was hypothesised that the preference of D. suzukii populations for fermentation cues like ACV is most pronounced during autumn, winter and spring, while the flies prefer fresh fruit cues during summer and that this seasonal preference is related to the changing physiology of the flies over the season. To test this hypothesis, the preference between fermentation cues (ACV) and host fruits (strawberries) and the effect of physiology (sex, seasonal morphology and feeding, mating and reproductive status) was investigated both in olfactometer laboratory experiments and a year-round field preference experiment. In olfactometer experiments we demonstrated that protein deprived females, virgin females with a full complement of unfertilised eggs and males show a strong preference for fermentation cues while fully fed reproductive summer morph females generally prefer fruit cues. These findings indicate that D. suzukii is attracted to fermentation volatiles in search of (protein-rich) food and to fruit volatiles in search of oviposition substrates. Winter morph and starved females displayed indiscriminating olfactory behaviour. In the field preference experiment, the hypothesised seasonal shift between fermentation and fruit cues was confirmed. This shift appeared to be highly temperature-related and was similarly observed for summer and winter morphs.
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A major problem in fruit cultivation in Flanders is replant disease due to a lack of uncultivated soils available for new plantings. Replant disease can cause poor growth and affect time to full production, however Arbuscular Mycorrhizal Fungi (AMF) can prove their usefulness with regard to these problems. To further investigate the effect of AMF on nematodes, different AMF species were amended to potted apple seedlings in the presence of the nematode Pratylenchus penetrans. Generally, apple seedlings grew better in the presence of nematodes when mycorrhiza were inoculated into the soil. Moreover, a positive correlation (R² ≥ 0.88) was found between the percentage root length colonization of the roots of apple seedlings, by AMF species, and nematode reduction in the soil of the seedlings. Indigenous AMF could colonize the roots of apple seedlings the most efficiently, resulting in a higher biocontrol effect. Besides, a synergistic effect was observed when two AMF strains were applied together leading to a significant growth response of the seedlings.