Peptaibiotics: Harnessing the potential of microbial secondary metabolites for mitigation of plant pathogens

[EN] 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.This work was funded by Fundacao para a Ciencia e Tecnologia (FCT) , through project "KIWIBOL-Looking Beyond KIWIfruit ESCA Complex to Define a PeptaiBOL-based Strategy to Disease Control", reference PTDC/ASP-PLA/2440/2021.Pereira-Dias, L.; Oliveira-Pinto, PR.; Fernandes, JO.; Regalado, L.; Mendes, R.; Teixeira, C.; Mariz-Ponte, N.... (2023). Peptaibiotics: Harnessing the potential of microbial secondary metabolites for mitigation of plant pathogens. Biotechnology Advances. 68. https://doi.org/10.1016/j.biotechadv.2023.1082236

Microglia dysfunction caused by the loss of Rhoa disrupts neuronal physiology and leads to neurodegeneration

© 2020 The Author(s). Creative Commons Attribution (CC BY 4.0)Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, producing a neurological phenotype (including synapse and neuron loss, impairment of long-term potentiation [LTP], formation of β-amyloid plaques, and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated tumor necrosis factor (TNF) production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also find that the Rhoa/Src signaling pathway is disrupted in microglia of the APP/PS1 mouse model of Alzheimer disease and that low doses of Aβ oligomers trigger microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing Rho GTPase signaling in microglia can directly cause neurodegeneration.The authors acknowledge the support of the following i3S Scientific Platforms: Animal Facility, Translational Cytometry Unit (TraCy), BioSciences Screening (BS) and Advanced Light Microscopy (ALM), and members of the national infrastructure PPBI-Portuguese Platform of BioImaging (supported by POCI-01–0145-FEDER-022122). FCT Portugal ( PTDC/MED-NEU/31318/2017-031318 ) supported work in the J.B.R. lab. FCT Portugal , PEst ( UID/NEU/04539/2013 ), COMPETE-FEDER ( POCI-01-0145-FEDER-007440 ), Centro 2020 Regional Operational Programme ( CENTRO-01-0145-FEDER-000008 : BrainHealth 2020), and Strategic Project UIDB/04539/2020 and UIDP/04539/2020 (CIBB) supported work in the A.F.A. lab. C.C.P. and R.S. hold employment contracts financed by national funds through FCT (Fundação para a Ciência e a Tecnologia, I.P.) in the context of the program contract described in paragraphs 4, 5, and 6 of article 23 of law no. 57/2016, of August 29th, as amended by law no. 57/2017 of July 19th.info:eu-repo/semantics/publishedVersio

Long-Term 3-Dimensional Stability of Mandibular Advancement Surgery

To evaluate the three-dimensional changes in the position of the condyles, rami, and chin from 1 to 3 years after mandibular advancement surgery

Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019): who’s being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.info:eu-repo/semantics/publishedVersio

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.info:eu-repo/semantics/publishedVersio

FORMAS DE PERCECIONAR A ESTRUTURA DE UM PROGRAMA DE MENTORIA

Introdução: No âmbito do projeto “Verão com Ciência”, financiado pela Fundação para a Ciência e a Tecnologia (FCT), o presente trabalho teve como objetivo desenvolver um guia orientador para a criação e implementação de um Programa de Mentoria (PM), enquanto promotor de práticas de inclusão em todas as Unidades Orgânicas (UO) da Instituição de Ensino Superior. Objetivos: Este artigo científico tem como objetivos: (i) Caracterizar o Programa de Mentoria implementado na Instituição de Ensino Superior através do projeto piloto em duas Unidades Orgânicas; (ii) Comparar a estrutura do PM implementado, com outras experiências e programas similares noutras instituições do ensino superior; (iii) Apresentar uma proposta de estrutura do PM a ser implementado na Instituição de Ensino Superior, a partir de setembro de 2020, de acordo com as melhorias e constrangimentos identificados, quer no projeto piloto, quer em experiências similares nas Universidades de Lisboa e Porto. Métodos: Estudo descritivo e exploratório, de natureza qualitativa. Análise dos dados recolhidos no projeto piloto “Práticas Inclusivas na Instituição de Ensino Superior”, bem como dados recolhidos por meio de entrevista semiestruturada, a dois mentores e quatro mentorados envolvidos em projetos de mentoria noutras instituições de ensino superior, com especial enfase na informação relativa à caracterização da implementação do PM. Revisão bibliográfica sobre a temática “Mentoria no Ensino Superior, associados ao estudo dos relatos recolhidos. (Silva et al., 2007). Resultados: Os resultados obtidos ao nível das duas principais categorias “Conceitos centrais à Mentoria” e “Caracterização do Programa de Mentoria” revelaram que algumas subcategorias e subespecificações semelhantes no estudo piloto e estudo atual estão de acordo com a literatura acerca da implementação de Programas de Mentoria. Conclusão: Perante a análise dos dados recolhidos, é possível afirmar que a implementação de programas de Mentoria é uma mais valia para o acolhimento dos estudantes recém-chegados e para a consolidação de boas práticas de inclusão no ensino superior.Introduction: Within the scope of the “Summer with Science” project, funded by the Foundation for Science and Technology (FCT), the present work aimed to develop a guiding guide for the creation and implementation of a Mentoring Program (PM), while promoter of inclusion practices in all Organic Units (OU) of the Higher Education Institution (HEI). Objectives: This scientific article aims to: (i) Characterize the Mentoring Program implemented at the Higher Education Institution through the pilot project in two Organic Units; (ii) Compare the structure of the implemented PM, with other experiences and similar programs in other higher education institutions; (iii) Present a proposal for a PM structure to be implemented at the Higher Education Institution, starting in September 2020, according to the improvements and constraints identified, both in the pilot project and in similar experiences at the Universities of Lisbon and Porto. Methods: Descriptive and exploratory study, of qualitative nature. Analysis of the data collected in the pilot project “Inclusive Practices at the Higher Education Institution”, as well as data collected through semi-structured interviews, with two mentors and four mentors involved in mentoring projects in other higher education institutions, with a special focus on information related to characterization of the PM implementation. Bibliographic review on the theme “Mentoring in Higher Education, associated with the study of the collected reports. (Silva et al., 2007). Results: The results obtained at the level of the two main categories “Concepts central to Mentoring” and “Characterization of the Mentoring Program” revealed that some similar subcategories and specifications emerged in the pilot study and current study are in accordance with the literature on the implementation of Programs of Mentoring. Conclusion: In view of the analysis of the data collected, it is possible to affirm that the implementation of Mentoring programs is an unavoidable asIntroducción: En el marco del proyecto “Verano con ciencia”, financiado por la Fundación para la Ciencia y la Tecnología (FCT), el presente trabajo tuvo como objetivo desarrollar una guía orientadora para la creación e implementación de un Programa de Mentoría (PM), mientras promotor de prácticas de inclusión en todas las Unidades Orgánicas (UO) de la institución de Ensino Superior. Objetivos: Este artículo científico tiene como objetivo: (i) Caracterizar el Programa de Mentoría implementado en el Instituição de Ensino Superior a través del proyecto piloto en dos Unidades Orgánicas; (ii) Comparar la estructura del PM implementado, con otras experiencias y programas similares en otras instituciones de educación superior; (iii) Presentar una propuesta para la implementación de una estructura de PM en el Instituição de Ensino Superior, a partir de septiembre de 2020, de acuerdo con las Coutinho, E., Loureiro, C., Mota, T., Loureiro, A., Contente, O., Peixoto, C., & Santos, P. M. (2020). Formas de percecionar a estrutura de um programa de mentoria. Millenium, 2(ed espec nº7), 35-43. DOI: 10.29352/mill0207e.04.00385 e7 37 37 mejoras y limitaciones identificadas, tanto en el proyecto piloto como en experiencias similares en las Universidades de Lisboa y Oporto. Métodos: Estudio descriptivo y exploratorio, de carácter cualitativo. Análisis de los datos recopilados en el proyecto piloto “Prácticas inclusivas en el Instituição de Ensino Superior”, así como datos recopilados a través de entrevistas semiestructuradas, con dos mentores y cuatro mentores involucrados en proyectos de mentoría en otras instituciones de educación superior, con especial énfasis en la información relacionada con caracterización de la implementación de PM. Revisión bibliográfica sobre el tema “Mentoring en Educación Superior, asociado al estudio de los informes recopilados. (Silva et al., 2007). Resultados: Los resultados obtenidos a nivel de las dos categorías principales “Conceptos centrales de la Mentoring” y “Caracterización del Programa de Mentoring” revelaron que algunas subcategorías y especificaciones similares surgieron en el estudio piloto y el estudio actual están de acuerdo con la literatura sobre la implementación de Programas. de tutoría. Conclusión: A la vista del análisis de los datos recolectados, es posible afirmar que la implementación de programas de Mentoring es un activo ineludible paraFundação para a Ciência e Tecnologiainfo:eu-repo/semantics/publishedVersio

An integrated green process for the extraction of triterpenic acids fromEucalyptus globulusleaves after hydrodistillation

In this study the viability of the integrated exploitation of E. globulus leaf essential oil and triterpenic acids was evaluated through the development of a novel extraction process that can be implemented sequentially in a biorefinery context. Thus, essential oil (EO) collected by hydrodistillation was used for the first time as a bio-based solvent to recover triterpenic acids (TTAs) from the residue resulting from the EO recovery (from the hydrodistilled leaves). Ursolic, oleanolic, betulonic and betulinic acids were successfully extracted with EO with, for comparison purposes, its major component, 1,8-cineole (CO), showing TTAs extraction yields of 2.8 and 2.7% dw, respectively. Both EO and CO were particularly efficient in extracting ursolic (18.3 and 17.9 g kg−1 dw) and oleanolic (6.0 and 5.7 g kg−1 dw, respectively) acids, the major components of crude extracts. In addition, cytotoxicity evaluation showed that EO and CO crude extracts are non-toxic to macrophage cell lines at concentrations less than or equal to 0.04 and 0.08 mg mL−1, respectively. Crude extracts dissolved in the EO and CO also showed higher antiinflammatory activity than a synthetic mixture representative of the TTAs detected, demonstrating the synergistic effect between EO or CO and the extracted components. In summary, the EO is a potential bio-based solvent, which could be applied in biorefinery processes, replacing organic solvents such as n-hexane in the recovery of TTAs, without environmental side effects, and even with potential applications of the crude extracts themselves in the nutraceutical and pharmaceutical fields.2021.03348.CEECIN

Long-Term 3-Dimensional Stability of Mandibular Advancement Surgery

To evaluate the three-dimensional changes in the position of the condyles, rami, and chin from 1 to 3 years after mandibular advancement surgery