Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 ...lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A
GM-CSF
double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF
CD4
cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF
and IL-17A
GM-CSF
double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.
Introduction
Cette étude a permis d’examiner les associations entre microfacteurs et consommation d’alcool ainsi que consommation excessive d’alcool au sein d’un vaste échantillon de jeunes ...Canadiens.
Méthodologie
Cette étude descriptive et analytique a porté sur les élèves du secondaire ayant participé à l’étude COMPASS entre 2012-2013 et 2017-2018. Nous avons utilisé la modélisation par équations d’estimation généralisées pour déterminer chez les répondants les associations entre les microfacteurs et la probabilité de consommer de l’alcool et de consommer de l’alcool de manière excessive plutôt que ne pas consommer d’alcool.
Résultats
Les élèves ayant déclaré consommer du cannabis étaient plus susceptibles de déclarer consommer de l’alcool plutôt que n’en avoir jamais consommé (rapport de cotes RC = 4,46; intervalle de confiance IC à 95 % : 4,33 à 4,60), comparativement aux élèves ayant indiqué ne pas consommer de cannabis. Les élèves ayant déclaré fumer du tabac étaient plus susceptibles de déclarer consommer de l’alcool de manière excessive plutôt que ne l’avoir jamais fait (RC = 2,52; IC à 95 % : 2,45 à 2,58), comparativement aux élèves non-fumeurs. Les élèves ayant déclaré disposer d’un revenu hebdomadaire de plus de 100 $ étaient plus susceptibles de déclarer consommer de l’alcool de manière excessive plutôt que de ne l’avoir jamais fait (RC = 2,14; IC à 95 % : 2,09 à 2,19), comparativement aux élèves ayant indiqué ne disposer d’aucun revenu hebdomadaire.
Conclusion
Un revenu disponible plus élevé, l’usage du tabac et la consommation de cannabis étaient associés à une consommation d’alcool et à une consommation excessive d’alcool chez les jeunes. Ces résultats peuvent éclairer la mise en place de mesures de prévention de l’usage de plusieurs substances dans les écoles secondaires.
Ecosystem restoration is a global priority, currently promoted by several ambitious commitments. Most of the research to guide restoration practices was so far put on the recovery of above‐ground ...functions and services, although soil health is increasingly recognized as a fundamental condition to restoration success. Soil restoration is particularly needed in mining areas, in which the surface soil layers are removed and the left over, highly deprived substrate does not support vegetation recovery.
Here, we evaluated the potential of active restoration to recover soil attributes after bauxite mining in the Brazil's Atlantic Forest. We specifically studied how physical, chemical and microbiological soil attributes down to 40 cm depth respond to restoration (i.e. topsoil spreading and tree planting) by comparing newly mined areas, areas undergoing restoration for ~7 years and conserved forests. We further explored the associations between microbiological and physico‐chemical soil attributes.
Restoration interventions resulted in a 10‐fold increase in the soil organic matter content compared to mined areas, as well as in the recovery of P content. Restoration was also shown to be associated with the recovery of the activity and diversity of soil bacterial communities, reaching similar levels to those observed in conserved forest. Restored and conserved forests were characterized by a higher proportion of Acidobacteria, Planctomycetes and Verrucomicrobia. All bacterial attributes were correlated with soil physical attributes, except for microporosity, and with organic matter and cation exchange capacity.
Within a few years, restoration allowed recovering crucial physical, chemical and microbiological soil attributes, reaching levels comparable to those found in conserved forests.
Synthesis and applications. We demonstrate that intensive management can result in the fast restoration of tropical forest soils after mining, at least at small scales. Our results stress the need to consider soil recovery both as a driver and a measure of ecosystem restoration success, and support the development of more holistic monitoring protocols to be used during the United Nations Decade on Ecosystem Restoration.
Resumo
A restauração de ecossistemas é uma prioridade global, atualmente promovida por vários compromissos ambiciosos. A maior parte da pesquisa para orientar as práticas de restauração foi até agora focada na recuperação de funções e serviços acima do solo, embora a saúde do solo seja cada vez mais reconhecida como uma condição fundamental para o sucesso da restauração. A restauração do solo é particularmente necessária em áreas de mineração, nas quais as camadas superficiais do solo são removidas e o substrato que sobra, altamente degradado, não suporta a recuperação da vegetação.
Neste estudo, avaliamos o potencial da restauração ativa para recuperar atributos do solo após a mineração de bauxita na Mata Atlântica do Brasil. Nós estudamos especificamente como os atributos físicos, químicos e microbiológicos do solo respondem à restauração até 40 cm de profundidade (ou seja, espalhamento de topsoil e plantio de árvores), comparando áreas recém‐mineradas, áreas em restauração por ~ 7 anos e florestas conservadas. Exploramos ainda as associações entre atributos microbiológicos e físico‐químicos do solo.
As intervenções de restauração resultaram em um aumento de 10 vezes no teor de matéria orgânica do solo em relação às áreas mineradas, bem como na recuperação do teor de P. A restauração também se mostrou associada à recuperação da atividade e diversidade das comunidades bacterianas do solo, atingindo níveis semelhantes aos observados nas florestas conservadas. Florestas restauradas e conservadas foram caracterizadas por uma maior proporção de Acidobacteria, Planctomycetes e Verrucomicrobia. Todos os atributos bacterianos foram correlacionados com os atributos físicos do solo, exceto com a microporosidade, e com matéria orgânica e capacidade de troca catiônica.
Em poucos anos, a restauração permitiu a recuperação de atributos físicos, químicos e microbiológicos cruciais do solo, atingindo níveis comparáveis aos encontrados em florestas conservadas.
Síntese e aplicações. Demonstramos que o manejo intensivo pode resultar na rápida restauração dos solos da floresta tropical após a mineração, pelo menos em pequena escala. Nossos resultados enfatizam a necessidade de considerar a recuperação do solo tanto como um impulsionador e uma medida do sucesso da restauração de ecossistemas, e para apoiar o desenvolvimento de protocolos de monitoramento mais holísticos a serem usados durante a Década das Nações Unidas para a Restauração de Ecossistemas.
We demonstrate that intensive management can result in the fast restoration of tropical forest soils after mining, at least at small scales. Our results stress the need to consider soil recovery both as a driver and a measure of ecosystem restoration success, and support the development of more holistic monitoring protocols to be used during the United Nations Decade on Ecosystem Restoration.
Introduction
Cette étude vise à examiner l’incidence de l’âge de la première consommation d’alcool sur la consommation actuelle d’alcool et les comportements connexes chez un large échantillon de ...jeunes Canadiens.
Méthodologie
Cette étude descriptive et analytique a été réalisée auprès d’élèves de 12e année de l’Ontario ayant participé à l’étude de référence COMPASS de 2012 à 2017. Nous avons eu recours à la modélisation par équations d’estimation généralisées (EEG) pour établir le lien entre l’âge de la première consommation d’alcool chez les répondants et la probabilité d’une consommation ou d’une absence de consommation d’alcool, d’une consommation excessive d’alcool et du mélange d’alcool et de boissons énergisantes.
Résultats
Les élèves ayant indiqué avoir consommé de l’alcool pour la première fois entre 13 et 14 ans étaient plus susceptibles de déclarer consommer de l’alcool plutôt que de ne pas en consommer (RC = 2,80, intervalle de confiance IC à 95 % : 2,26 à 3,45) et étaient plus susceptibles de déclarer consommer de l’alcool de façon excessive plutôt que de ne pas en consommer de façon excessive (RC = 3,22, IC à 95 % : 2,45 à 4,25) comparativement aux élèves ayant déclaré avoir consommé de l’alcool pour la première fois à 18 ans ou plus. Les élèves ayant commencé à consommer de l’alcool à 8 ans ou moins étaient plus susceptibles de déclarer consommer de l’alcool plutôt que de ne pas en consommer (RC = 3,54, IC à IC à 95 % : 2,83 à 4,43), avoir une consommation excessive d’alcool (RC = 3,99, IC à IC à 95 % : 2,97 à 5,37) et mélanger alcool et boissons énergisantes (RC = 2,26, IC à IC à 95 % : 1,23 à 4,14) comparativement aux élèves ayant commencé à consommer de l’alcool à 18 ans ou plus.
Conclusion
La consommation d’alcool pendant les premières années de l’adolescence permet de prédire la consommation d’alcool, la consommation excessive d’alcool ainsi que la tendance à mélanger alcool et boissons énergisantes lorsque les élèves arrivent en 12e année. Ces résultats soulignent le besoin de déployer de nouveaux efforts de prévention de la consommation d’alcool.
Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight ...transcriptional control to preserve their structure, identity, and functions. We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. Subsequent antisense oligonucleotide-knockdown transcriptomic profiling of two LEC- and two BEC-specific lncRNAs identifies LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein interaction studies, and phenotype rescue analyses reveal that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides several lines of evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.
To determine the microRNA (miR) signature in ankylosing spondylitis (AS) T helper (Th)17 cells.
Interleukin (IL)-17A-producing CD4+ T cells from patients with AS and healthy controls were FACS-sorted ...for miR sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays.
AS Th17 cells exhibited a miR signature characterised by upregulation of miR-155-5p, miR-210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterisation. miR-10b is transiently induced in in vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b overexpression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells.
AS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by proinflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in patients with AS.
This paper applies a methodology for interdisciplinary Facilities Management (FM) by alingment between Building Information Modeling (BIM) and Lean. Initially, the literature review of BIM, FM and ...Lean principles. Afterwards, the research applies the Digital Obeya Room for improved FM and describes its application on a real-world case study. Lastly, the work presents a survey with specialists to assess the relevance of each BIM-Lean concepts and correlate their perceptions with the empirical results. The main collaborations of this work are: a conceptual framework that relates the PDCA (Plan-Do-Check-Act) cycle with BIM-Lean approaches; the identification of the most relevant BIM functionalies and Lean principles; and the real-world application of the framework procedures on FM.
Ovarian cancer is the most deadly gynecological malignancy. Understanding the molecular pathogenesis of ovarian cancer is critical to provide new targeted therapeutic strategies. Recent evidence ...supports a role for Notch in ovarian cancer progression and associates its dysregulation to poor overall survival. Similarly, CXCR4/SDF1α signalling correlates with ovarian cancer progression and metastasis. Recent findings indicate that Notch promotes CXCR4/SDF1α signalling and its effect on cell growth and migration; nonetheless, up to now, the association between Notch and CXCR4/SDFα in ovarian cancer has not been reported. Thereby, the aim of this study was to investigate if Notch and CXCR4/SDF1α cooperate in determining ovarian cancer growth, survival and migration.
To address this issue, Notch signalling was inhibited by using γ-secretase inhibitors, or upregulated by forcing of Notch1 expression in ovarian cancer cell lines. Our results indicated that Notch activity influenced tumour cell growth and survival and positively regulated CXCR4 and SDF1α expression. CXCR4/SDF1α signalling mediated the effect of Notch pathway on ovarian cancer cell growth and SDF1α-driven migration. Additionally, for the first time, we demonstrated that Notch signalling activation can be detected in ovarian cancer specimens by immunohistochemistry analysis of the Notch transcriptional target, HES6 and is positively correlated with high expression levels of CXCR4 and SDF1α.
Our results demonstrate that Notch affects ovarian cancer cell biology through the modulation of CXCR4/SDF1α signalling and suggest that Notch inhibition may be a rationale therapeutic approach to hamper ovarian cancer progression mediated by the CXCR4/SDF1α axis.
Introduction
Bone consolidation defects represent a real orthopedic challenge because of the absence of validated treatment guidelines that can assist the surgeon in his choices. The aim of this ...study is to evaluate the appropriateness of the Non-Union Scoring System NUSS treatment protocol in the management of long bone non-unions by comparing it to the experience-based therapeutic approach carried out in our facility.
Materials and Methods
We conducted a comparative outcome study of a retrospective series of 89 patients surgically treated for long bone non-union in our facility vs. clinical results reported by Calori et al. obtained following the NUSS treatment protocol.
Results
Radiographic healing was reached in 13/13 non-unions (100%) in group NUSS 1, in 58/62 (93.5%) in group NUSS 2, and in 13/14 (92.9%) in group NUSS 3. The mean time to radiographic healing was 5.69 ± 2.09 months in group 1, 7.38 ± 3.81 months in group 2 and 9.23 ± 2.31 months in group 3. 91% of patients in group I, 69% in group II and 48% in group III received what would be considered by the NUSS treatment protocol an “overtreatment”, especially from a biological stand point. The comparative outcome analysis shows that our case series achieved significantly higher global healing rates (
p
value = 0.017) and shorter radiological healing times in groups NUSS 1 and 2 (
p
value < 0.001).
Conclusion
From the results obtained, we can assume that the NUSS treatment protocol might underestimate the necessary therapies, particularly from a biological point of view.
Soil phosphorus (P) is a major driver of forest development and a critically limited nutrient in tropical soils, especially when topsoil is removed by mining. This nutrient can be present in soils in ...the form of different fractions, which have direct consequences for P availability to plants and, consequently, for restoration success. Therefore, understanding how the stocks of different soil P fractions change over the restoration process can be essential for guiding restoration interventions, monitoring, and adaptive management. Here, we investigated the recovery of soil P fractions by forest restoration interventions on bauxite mine sites in the Brazilian Atlantic Forest. We assessed the concentration of different fractions of soil organic and inorganic P at (1) a bauxite mine prepared for restoration; (2) two former bauxite mines undergoing forest restoration for 6 and 24 years; and (3) an old‐growth forest remnant. Overall, restored areas recovered levels of labile organic P (Po‐NaHCO3) at 5–40 cm and of moderately labile organic P (Po‐NaOH) at different depths, exhibiting concentrations similar to those found in a conserved forest. The use of P‐rich fertilizers and forest topsoil may have greatly contributed to this outcome. Some other fractions, however, recovered only after 24 years of restoration. Other inorganic P fractions did not differ among mined, restored, and conserved sites: nonlabile Pi (residual P and P‐HCl), labile Pi (Pi‐NaHCO3), and moderately labile Pi (Pi‐NaOH). Forest restoration was able to promote efficient recovery of important soil P fractions, highlighting the value of restoration efforts to mitigate soil degradation by mining.
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