120 research outputs found

    Sustainable management of coastal sand dunes to human activities and natural disasters in Oregon, the United States

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    Dune destabilization became a socio-economic issue as Euro-Americans settled in Oregon in the 19th century. Non-native Ammophila arenaria and Ammophila breviligulata were widely used for stabilization from the early-20th century. As non-native beachgrasses turned invasive causing the loss of biodiversity and habitats, their removal became the focus to regain the active dunes to support the natural processes of the ecosystem. In this work we aimed to understand the response of coastal sand dunes to natural hazards (e.g. sea-level rise), human activities (e.g. settlement, urbanization and animal husbandry) and dune management initiatives (e.g. planting of non-native beachgrasses) in Oregon in the United States during two contrasting periods: 1) from the 19th to late-20th century and 2) from there to the early-21st century.info:eu-repo/semantics/publishedVersio

    Genetic variation in PFKFB3 impairs antifungal immunometabolic responses and predisposes to Invasive Pulmonary Aspergillosis

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    Copyright © 2021 Gonçalves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.Activation of immune cells in response to fungal infection involves the reprogramming of their cellular metabolism to support antimicrobial effector functions. Although metabolic pathways such as glycolysis are known to represent critical regulatory nodes in antifungal immunity, it remains undetermined whether these are differentially regulated at the interindividual level. In this study, we identify a key role for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the immunometabolic responses to Aspergillus fumigatus. A genetic association study performed in 439 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) and corresponding donors revealed that the donor, but not recipient, rs646564 variant in the PFKFB3 gene increased the risk of invasive pulmonary aspergillosis (IPA) after transplantation. The risk genotype impaired the expression of PFKFB3 by human macrophages in response to fungal infection, which was correlated with a defective activation of glycolysis and the ensuing antifungal effector functions. In patients with IPA, the risk genotype was associated with lower concentrations of cytokines in the bronchoalveolar lavage fluid samples. Collectively, these findings demonstrate the important contribution of genetic variation in PFKFB3 to the risk of IPA in patients undergoing HSCT and support its inclusion in prognostic tools to predict the risk of fungal infection in this clinical setting. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. Activation of glycolysis is essential for innate immune cells to mount effective antifungal responses. In this study, we report the contribution of genetic variation in the key glycolytic activator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) to the risk of invasive pulmonary aspergillosis (IPA) after allogeneic hematopoietic stem cell transplantation. The PFKFB3 genotype associated with increased risk of infection was correlated with an impairment of the antifungal effector functions of macrophages in vitro and in patients with IPA. This work highlights the clinical relevance of genetic variation in PFKFB3 to the risk of IPA and supports its integration in risk stratification and preemptive measures for patients at high risk of IPA.This work was supported by the Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-SER/29635/2017, PTDC/MED-GEN/28778/2017, UIDB/50026/2020, and UIDP/50026/2020), the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000039), the Institut Mérieux (Mérieux Research Grant 2017), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017), the European Union’s Horizon 2020 research and innovation program under grant agreement no. 847507, and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003. Individual support was provided by FCT (SFRH/BD/136814/2018 to S.M.G., PD/BD/137680/2018 to D.A., CEECIND/04058/2018 to C.C., and CEECIND/03628/2017 to A.C.). M.G.N. was supported by an ERC Advanced Grant and a Spinoza Grant of the Netherlands Organization for Scientific Research.info:eu-repo/semantics/publishedVersio

    A atitude do educador de infância e a participação da criança como referenciais de qualidade em educação

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    Neste artigo, fundamentado em dois estudos de caso em jardim de infância, refletiu- -se sobre como e com quais ferramentas de apoio se pode avaliar e promover qualidade e intervenção educativa adequada nos contextos. Selecionou-se um grupo de crianças (entre 3 e 6 anos) e desenvolveram-se estratégias com a finalidade de escutar e compreender o modo como elas participam. Ainda, em diversos tempos da rotina de cada contexto, identificaram-se interações e atitudes do educador, analisando-se o respetivo impacto no nível da participação das crianças. Os resultados revelaram que, quando as crianças desenvolvem um sentimento de pertença ao contexto e lhes são oferecidas oportunidades de participação, mais facilmente se envolvem, revelam bem-estar emocional e motivação para aprender, explorar e participar nos processos de tomada de decisão. A escuta ativa, o questionamento e o encorajamento do diálogo assumem-se, por parte do adulto, competências essenciais para a qualidade da intervenção educativa.This paper, based on two case studies in a kindergarten context, describes a reflection on the most appropriate method and tools for the assessment and promotion of quality and context intervention. A group of children (between 3 and 6 years old) was selected and strategies were developed in order to listen to the children’s voices and understand how they were participating. Moreover, in different routine times within each context, interactions and attitudes of educators were identified, with the corresponding analysis of the impact on children’s participation. The results revealed that when children develop a sense of belonging in the context and they are offered opportunities to participate, they more easily get engaged, reveal emotional wellbeing and motivation to learn, explore and participate in decision-making processes. For the adult, active listening, questioning and encouragement of dialogue appear as essential skills to promote quality in educational intervention.En el presente artículo, basado en dos estudios de caso en un jardín de infancia, se reflexionó sobre cómo y con qué herramientas de apoyo se puede evaluar y promover calidad e intervención educativa apropiada en los contextos. Se seleccionó un grupo de niños (entre los 3 y 6 años de edad) y se desarrollaron estrategias con la finalidad de escuchary comprender el modo como dichos niños participan. Además, en diversos momentos de la rutina de cada contexto, se identificaron interacciones y actitudes del educador, analizando el respectivo impacto en la participación de los infantes. Los resultados revelaron que, cuando los niños desarrollan un sentido de pertenencia al contexto y se les ofrece la oportunidad de participar, más fácilmente se envuelven, revelan bienestar emocional y motivación para aprender, explorar y participar en la toma de decisiones. La escucha activa, el cuestionar y fomentar el diálogo constituyen, para el adulto, competencias esenciales para la calidad de la intervención educativa

    A Spitzer Space Telescope far-infrared spectral atlas of compact sources in the Magellanic Clouds. I. The Large Magellanic Cloud

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    [abridged] We present 52-93 micron spectra obtained with Spitzer in the MIPS-SED mode, of a representative sample of luminous compact far-IR sources in the LMC. These include carbon stars, OH/IR AGB stars, post-AGB objects and PNe, RCrB-type star HV2671, OH/IR red supergiants WOHG064 and IRAS05280-6910, B[e] stars IRAS04530-6916, R66 and R126, Wolf-Rayet star Brey3a, Luminous Blue Variable R71, supernova remnant N49, a large number of young stellar objects, compact HII regions and molecular cores, and a background galaxy (z~0.175). We use the spectra to constrain the presence and temperature of cold dust and the excitation conditions and shocks within the neutral and ionized gas, in the circumstellar environments and interfaces with the surrounding ISM. Evolved stars, including LBV R71, lack cold dust except in some cases where we argue that this is swept-up ISM. This leads to an estimate of the duration of the prolific dust-producing phase ("superwind") of several thousand years for both RSGs and massive AGB stars, with a similar fractional mass loss experienced despite the different masses. We tentatively detect line emission from neutral oxygen in the extreme RSG WOHG064, with implications for the wind driving. In N49, the shock between the supernova ejecta and ISM is revealed by its strong [OI] 63-micron emission and possibly water vapour; we estimate that 0.2 Msun of ISM dust was swept up. Some of the compact HII regions display pronounced [OIII] 88-micron emission. The efficiency of photo-electric heating in the interfaces of ionized gas and molecular clouds is estimated at 0.1-0.3%. We confirm earlier indications of a low nitrogen content in the LMC. Evidence for solid state emission features is found in both young and evolved object; some of the YSOs are found to contain crystalline water ice.Comment: Accepted for publication in The Astronomical Journal. This paper accompanies the Summer 2009 SAGE-Spec release of 48 MIPS-SED spectra, but uses improved spectrum extraction. (Fig. 2 reduced resolution because of arXiv limit.

    IL-10 overexpression predisposes to invasive aspergillosis by suppressing antifungal immunity

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    © 2017 American Academy of Allergy, Asthma & ImmunologyProinflammatory immune responses are critically required for antimicrobial host defenses; however, excessive inflammation has the potential to damage host tissues thereby paradoxically contributing to the progression of infection. A central negative regulator of inflammatory responses is IL-10, an immunosuppressive cytokine with a wide variety of functions across multiple cell types. Although the role of IL-10 during infection appears to vary for different microorganisms, a largely detrimental role has been attributed to this cytokine during fungal disease. Given the variable risk of infection and its outcome among patients with comparable predisposing factors, susceptibility to invasive aspergillosis (IA) is thought to rely largely on genetic predisposition. The initial investigation of genetic variability at the IL10 locus led to the identification of single nucleotide polymorphisms (SNPs) influencing its transcriptional activity; thus, IL-10 may be a reasonable candidate for the genetic regulation of susceptibility to IA in high-risk patients.Supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (contracts IF/00735/2014 to A.C., IF/01390/2014 to E.T., IF/00021/2014 to R.S., and SFRH/BPD/96176/2013 to C.C.), the Conselho de Reitores das Universidades Portuguesas (CRUP), Portugal (Ações Integradas Luso-Alemãs A-43/16), the Deutscher Akademischer Austauschdienst (DAAD) (project-ID 57212690), the Fondo de Investigaciones Sanitarias (Madrid, Spain) (grant #PI12/02688) and the ERA-NET PathoGenoMics (grant #0315900A).info:eu-repo/semantics/publishedVersio

    Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus

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    Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451062/We propose a novel, non-discriminatory classification of monkeypox virus diversity. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within IIb, the cause of the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomic surveillance.info:eu-repo/semantics/publishedVersio

    Inhibitors of trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

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    Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi

    Adapting Agriculture to Climate Change: A Synopsis of Coordinated National Crop Wild Relative Seed Collecting Programs across Five Continents

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    The Adapting Agriculture to Climate Change Project set out to improve the diversity, quantity, and accessibility of germplasm collections of crop wild relatives (CWR). Between 2013 and 2018, partners in 25 countries, heirs to the globetrotting legacy of Nikolai Vavilov, undertook seed collecting expeditions targeting CWR of 28 crops of global significance for agriculture. Here, we describe the implementation of the 25 national collecting programs and present the key results. A total of 4587 unique seed samples from at least 355 CWR taxa were collected, conserved ex situ, safety duplicated in national and international genebanks, and made available through the Multilateral System (MLS) of the International Treaty on Plant Genetic Resources for Food and Agriculture (Plant Treaty). Collections of CWR were made for all 28 targeted crops. Potato and eggplant were the most collected genepools, although the greatest number of primary genepool collections were made for rice. Overall, alfalfa, Bambara groundnut, grass pea and wheat were the genepools for which targets were best achieved. Several of the newly collected samples have already been used in pre-breeding programs to adapt crops to future challenges.info:eu-repo/semantics/publishedVersio
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