Agricultural systems are in need of low-cost, safe antibiotics to protect crops from pests and diseases. Peptaibiotics, a family of linear, membrane-active, amphipathic polypeptides, have been shown ...to exhibit antibacterial, antifungal, and antiviral activity, and to be inducers of plant resistance against a wide range of phytopathogens. Peptaibiotics belong to the new generation of alternatives to agrochemicals, aligned with the United Nations Sustainable Development Goals and the One Health approach toward ensuring global food security and safety. Despite that, these fungi-derived, non-ribosomal peptides remain surprisingly understudied, especially in agriculture, where only a small number has been tested against a reduced number of phytopathogens. This lack of adoption stems from peptaibiotics’ poor water solubility and the difficulty to synthesize and purify them in vitro, which compromises their delivery and inclusion in formulations. In this review, we offer a comprehensive analysis of peptaibiotics’ classification, biosynthesis, relevance to plant protection, and mode of action against phytopathogens, along with the techniques enabling researchers to extract, purify, and elucidate their structure, and the databases holding such valuable data. It is also discussed how chemical synthesis and ionic liquids could increase their solubility, how genetic engineering and epigenetics could boost in vitro production, and how omics can reduce screenings’ workload through in silico selection of the best candidates. These strategies could turn peptaibiotics into effective, ultra-specific, biodegradable tools for phytopathogen control.
•Peptaibiotics’ are bioactive against a wide range of phytopathogens.•Peptaibiotics’ poor water solubility compromises their delivery and inclusion in formulations.•Novel techniques, like chemical synthesis and ionic liquids, could increase their solubility.•Genetic engineering and epigenetics could boost peptaibiotics’ in vitro production.•Omics can reduce screenings’ workload through in silico genome mining selection of best isolate and molecule.
The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with ...moderate to severe asthma.
A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing (Bruce protocol) and lung function.
No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p < 0.05). Although the mean energy expenditure at rest and during exercise training was similar for both groups, the maximum energy expenditure was higher in the VGG.
The present findings strongly suggest that aerobic training promoted by an active video game had a positive impact on children with asthma in terms of clinical control, improvement in their exercise capacity and a reduction in pulmonary inflammation.
Clinicaltrials.gov NCT01438294.
Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is ...the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectively; conversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37°C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work unravels (i) interesting physiological property of C. neoformans regarding its amino acid uptake system; (ii) an important aspect of virulence, which is the need for amino acid permeases during thermal and oxidative stress resistance and, hence, host invasion and colonization; and (iii) provides a convenient prototype for antifungal development, which are the amino acid permeases Aap4/Aap5 and their inhibitor.
The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators ...upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.
Genetic mutations and aging-associated oxidative damage underlie the onset and progression of neurodegenerative diseases, like Parkinson’s disease (PD) and Machado-Joseph disease (MJD). Natural ...products derived from plants have been regarded as important sources of novel bioactive compounds to counteract neurodegeneration. Here, we tested the neuroprotective effect of an ethanolic extract of rapeseed pomace (RSP), a rapeseed (canola) oil production by-product, in
C. elegans
models of MJD and PD. The extract, containing sinapine and other phenolics, restored motor function of mutant ataxin-3 (ATXN3) animals (MJD) and prevented degeneration of dopaminergic neurons in one toxin-induced and two genetic models of PD. Whole-organism sensors of antioxidant and xenobiotic response activation revealed the induction of phase II detoxification enzymes, including glutathione S- transferase (GST-4) upon RSP extract supplementation. Furthermore
in vivo
pharmacogenetic studies confirmed
gst-4
is required for the therapeutic effect of RSP extract in the two disease models. The results suggest that GST-4-mediated antioxidant pathways may constitute promising therapeutic co-targets for neurodegenerative diseases and confirm the utility of searching for bioactive compounds in novel sources, including food and agricultural waste/by-products, such as RSP.
This study aimed to develop and evaluate a pooled antigen for use in the macroscopic slide agglutination test (MSAT) to detect cattle positive for the Sejroe serogroup. To this end, 193 bovine serum ...samples from different Pará State regions (Amazonia) were subjected to a reference microscopic agglutination test (MAT) for the serological diagnosis of leptospirosis using 11 serovars representing the Sejroe serogroup: Hardjo-prajitno; Hardjo-bovis; Sejroe; Wolffi; Guaricura (Bov.G.); Guaricura (M4/98); Ricardi; Gorgas; Recreo; Polonica and Medanensis. The three most prevalent serovars in the MAT were selected for the development of a pooled antigen for use in MSAT; subsequently, the 193 serum were assessed with the macroscopic slide agglutination test (MSAT) containing the developed antigen. The Kappa test was used to determine the general agreement between the MAT and MSAT results. As a result, of the 193 serum samples, 155 (80.3%) were reactive, and 38 (19.7%) were non-reactive in the MAT; Hardjo-prajitno, Wolffi and Medanensis were the three most prevalent serovars. Of the 193 serum samples tested in the MSAT using the developed pooled antigen, 114 were reactive (59.0%), and 79 (41.0%) were non-reactive; the Kappa coefficient was 0.52 (CI 95%, 0.40–0.63), indicating moderate agreement between the two tests. The MSAT with the pooled antigen including the most prevalent serovars detected bovines with the Sejroe serogroup exposure, mainly in animals with high titters in the MAT, and could be used to screen herds suspected of acute infection by this serogroup in Pará State.
•The macroscopic slide agglutination test (MSAT) was first used in Brazil to detect cattle exposed to Sejroe serogroup.•The pooled antigen used on MSAT was composed by Hardjo-prajitno, Wolffi and Medanensis serovars.•The addition of Ponceau S dye to pooled antigen favored the visualization of reactive samples.•The MSAT using this developed antigen could be used for initial screening in herds in Amazonia, especially in remote areas.
Objectives
The goal of this study was to assess the newly formed bone and the remnant biomaterial by comparing four different bone grafts used to treat critical‐size defects, associated or not with ...the non‐resorbable membrane.
Materials and Methods
Two calvaria critical‐size bone defects were created in 50 male Wistar rats. They were divided into blood (G1), autogenous (G2), bioglass (G3), hydroxyapatite (G4), and xenograft (G5) groups, associated or not with e‐PTFE. The experimental periods were 15 and 45 days. Sections were prepared for histomorphometric assessment. All data were analyzed by the mixed‐effects model with multiple comparisons (significance level, p < .05).
Results
A similar level of new bone was observed for all groups, associated with a high level of vascularization. G1 and G2 ensured sovereignty over the greater quantity of new bone. A non‐significant result was reported comparing groups with and without membranes. No significant result was found between the experimental synthetic biomaterials (G3 and G4). G5L achieved 22.0% of new bone after 45 days (p > .05). All groups had a stable volume of biomaterial kept in the short term (p > .05). G2 was the best material for new bone formation and final volume of biomaterial, followed by G4 < G5 < G3. Thus, it is possible that G4 had a better degradation profile among the experimental groups.
Conclusions
The best results were found in the autogenous group, with higher resorption and integration; non‐significative new bone was found among the experimental groups; and the regeneration of critical bone defects using an e‐PTFE barrier did not present significant results on new bone formation.
O objetivo deste artigo é analisar as notícias publicadas sobre o slow fashion em websites especializados no jornalismo de moda e identificar como o jornalismo especializado de/em moda vem sendo um ...importante vetor de informação e conscientização ética sobre o consumo responsável nas sociedades ocidentais do século XXI. Para tanto, por meio de pesquisa básica, qualitativa e descritiva, empreendeu-se uma análise de conteúdo comparativa de três blogs especializados em moda: (I) Moda sem crise, (II) Modefica e (III) Stylo urbano, a partir de notícias e reportagens sobre o movimento slow fashion. Os resultados apontaram que, apesar desses websites apresentarem majoritariamente tendências de moda como looks do dia e cartelas de cores ditados por blogueiras, estes se revelam como frutíferos espaços midiáticos para abordagens mais conscientes e alternativas sustentáveis nos conteúdos de moda apresentados.
Introdução: O distúrbio neurocognitivo associado ao HIV (HAND) é caracterizado pelo comprometimento progressivo das funções neurológicas, cuja incidência varia entre 15 a 50% das pessoas vivendo com ...HIV/AIDS (PVHA). Dados clínicos, laboratoriais e fatores sociodemográficos podem corroborar no entendimento da HAND, sendo um passo fundamental para aprimorar o diagnóstico e prognóstico, tratamento e o acompanhamento dos pacientes desta coorte. O objetivo deste estudo é identificar fatores clínicos, laboratoriais e sociodemográficos de PVHA, que possam estar associados a HAND. Metodologia: Foram incluídos 24 participantes provenientes do ambulatório de Imunodeficiências Secundárias (ADEE 3002) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) neste estudo. Os dados demográficos foram coletados no momento da apresentação da pesquisa e assinatura do TCLE e os dados clínicos e laboratoriais de interesse foram coletados através do HCMED. A análise estatística foi feita através do software GraphPad Prism® v.9. Utilizou-se os testes Shapiro-Wilk para analisar a normalidade dos dados, Teste T independente com correção de Welch para a comparação entre os grupos e o teste exato de Fisher para a análise de dados baseados em frequências. Resultados: A análise dos dados sociodemográficos revelou que a média de idade dos participantes foi de 46,8 anos (± 9,8), com uma predominância de 79,2% de mulheres e 20,8% de homens. A escolaridade média foi de 11,1 anos (± 3,7). Em relação aos dados laboratoriais, não foram observadas diferenças estatísticas significativas. No entanto, houve uma tendência de diminuição na contagem de linfócitos T CD4+ no grupo HAND (688, ± 286 cels/mm3) em relação ao grupo normal (1011 ± 474 cels/mm3), assim como no nadir das células T CD4+, no grupo HAND (254 ± 204 cels/mm3) em comparação com o grupo normal (405 ± 290 cels/mm3). Quanto aos demais parâmetros clínicos analisados (tempo de tratamento, regime antirretroviral, e comorbidades) entre as categorias de classificação neurocognitiva, também não foram encontradas diferenças estatísticas. Conclusão: Após análise exploratória das características sociodemográficas e clínicas em PVHA, esses achados sugerem que os fatores clínicos investigados podem não estar diretamente associados ao desenvolvimento da HAND, ou seja, é multifatorial, requer estudos adicionais para uma compreensão mais aprofundada dessa relação e ou um biomarcador.
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