Abordagem por Competências no Currículo Escolar em Cabo Verde: Desfazendo Equívocos para uma Mudança Significativa nas Políticas e Práxis Educacionais

A abordagem curricular por competências, enquanto fenómeno recente no discurso educativo em Cabo Verde, corre o risco de não passar de mero modismo, sem se traduzir numa inovação efectiva ao nível das práxis educacionais, se não for correctamente compreendida pelos diversos actores envolvidos na obra educativa e, em particular, nos processos de deliberação, gestão e realização dos currículos escolares. O presente artigo procura esclarecer alguns equívocos que em Cabo Verde, como em outras latitudes, acompanham a defesa da pedagogia por competências. Assim, importa elucidar que a abordagem curricular por competências vem aprofundar, entre outras, as abordagens por conteúdos e por objectivos e não, pura e simplesmente, substituí-las, por serem, alegadamente, tradicionais. Outrossim, no contexto da educação escolar, as competências não devem ser encaradas numa perspectiva redutora, focalizada na transferibilidade de conhecimentos para o mercado de trabalho, mas, fundamentalmente, no sentido da mobilização do conhecimento escolar para a resolução dos problemas nos diversos contextos ou situações da vida, que não se esgota no mercado

Caractérisation du rôle des vésicules extracellulaires sur le microenvironnement du lymphome folliculaire

Extracellular vesicles (EVs) are membrane-derived vesicles originating from multiple cellular pathways and exhibiting diverse content and nature. EVs are endowed with protumoral activities such as metabolism modification, immune escape, metastasis, and microenvironment reprogramming. Recent studies have shown that EVs contribute to the polarisation of tumor-infiltrating fibroblasts into pro-tumor supportive cells. This has been reported in particular in lymphoid malignancies developing within bone marrow (BM), such as multiple myeloma and chronic lymphocytic leukaemia. Follicular lymphoma is the most common indolent B-cell lymphoma, developing as a disseminated disease infiltrating lymph nodes (LN) and bone marrow (BM). This B-cell malignancy is strongly dependent on a germinal center-like permissive microenvironment exhibiting FL-specific features and driving the FL-supportive niche. Accordingly, the FL BM niche is characterized by an ectopic differentiation of lymphoid-like stromal cells and a local enrichment in CD4+ T cells, both reminiscent of LN follicular organization. However, the early driver mechanisms triggering the formation of this medullar FL permissive niche has not been yet identified. In the current work, we report that FL B cells produce EVs that could be internalized by BM mesenchymal stromal cells (BM-MSC), making them more efficient to support FL B-cell survival. Moreover, this supportive phenotype is different from that obtained under TNF/LT stimulation, the main driver of lymphoid stroma differentiation, and includes a strong upregulation of genes previously involved in the hematopoietic stem cell niche. Finally, BM-MSC priming by FL-derived EVs contribute to the selection of FL B cells with a quiescent phenotype mimicking those of BM FL B cells, supporting a role of EVs in FL dissemination and drug resistance.Les vésicules extracellulaires (EVs) sont des vésicules membranaires de contenu et de nature diverse, provenant de multiples voies cellulaires. Ces EVs sont impliquées dans de nombreux processus contribuant à la cancérogenèse tels que la modification du métabolisme, l'échappement immunitaire, la formation de métastases et la reprogrammation du microenvironnement. Des études récentes ont en particulier démontré que les EVs contribuent à reprogrammer les cellules fibroblastiques du microenvironnement en cellules de soutien pro-tumoral. Ceci a notamment été rapporté dans les hémopathies lymphoïdes se développant dans la moelle osseuse (BM), comme le myélome multiple et la leucémie lymphoïde chronique. Le lymphome folliculaire (FL), qui est le lymphome à cellules B indolent le plus fréquent se développe comme une maladie disséminée infiltrant les ganglions lymphatiques (LN) et la BM. Cette hémopathie B dépend fortement d'un microenvironnement permissif proche de celui des centres germinatifs normaux des LN mais présentant des caractéristiques spécifiques de soutien du FL. En ce sens, la niche médullaire du FL est caractérisée par une différenciation ectopique de cellules stromales lymphoïdes et un enrichissement local en cellules T CD4+, rappelant toutes deux l'organisation folliculaire ganglionnaire. Cependant, le déterminant déclenchant la formation de cette niche folliculaire permissive dans la BM n'a pas encore été identifié. Dans ce travail, nous démontrons que les cellules B de FL produisent des EVs qui sont internalisées par les cellules stromales mésenchymateuses médullaires (BM-MSC), ce qui les rend plus efficaces pour soutenir la survie des cellules B malignes. Par ailleurs, ce phénotype de soutien est différent de celui obtenu par la stimulation TNF/LT, inductrice de la différentiation en stroma lymphoide, et comprend une induction forte de gènes précédemment impliqués dans la niche des cellules souches hématopoïétiques. Enfin, le traitement des BM-MSC par les EVs dérivées du FL contribue à la sélection de cellule B tumorales quiescentes imitant celles des cellules B de FL médullaires, et soutenant un rôle des EVs dans la dissémination du FL et la résistance au traitement

Characterisation of the role of extracellular vesicles on follicular lymphoma microenvironment

Les vésicules extracellulaires (EVs) sont des vésicules membranaires de contenu et de nature diverse, provenant de multiples voies cellulaires. Ces EVs sont impliquées dans de nombreux processus contribuant à la cancérogenèse tels que la modification du métabolisme, l'échappement immunitaire, la formation de métastases et la reprogrammation du microenvironnement. Des études récentes ont en particulier démontré que les EVs contribuent à reprogrammer les cellules fibroblastiques du microenvironnement en cellules de soutien pro-tumoral. Ceci a notamment été rapporté dans les hémopathies lymphoïdes se développant dans la moelle osseuse (BM), comme le myélome multiple et la leucémie lymphoïde chronique. Le lymphome folliculaire (FL), qui est le lymphome à cellules B indolent le plus fréquent se développe comme une maladie disséminée infiltrant les ganglions lymphatiques (LN) et la BM. Cette hémopathie B dépend fortement d'un microenvironnement permissif proche de celui des centres germinatifs normaux des LN mais présentant des caractéristiques spécifiques de soutien du FL. En ce sens, la niche médullaire du FL est caractérisée par une différenciation ectopique de cellules stromales lymphoïdes et un enrichissement local en cellules T CD4+, rappelant toutes deux l'organisation folliculaire ganglionnaire. Cependant, le déterminant déclenchant la formation de cette niche folliculaire permissive dans la BM n'a pas encore été identifié. Dans ce travail, nous démontrons que les cellules B de FL produisent des EVs qui sont internalisées par les cellules stromales mésenchymateuses médullaires (BM-MSC), ce qui les rend plus efficaces pour soutenir la survie des cellules B malignes. Par ailleurs, ce phénotype de soutien est différent de celui obtenu par la stimulation TNF/LT, inductrice de la différentiation en stroma lymphoide, et comprend une induction forte de gènes précédemment impliqués dans la niche des cellules souches hématopoïétiques. Enfin, le traitement des BM-MSC par les EVs dérivées du FL contribue à la sélection de cellule B tumorales quiescentes imitant celles des cellules B de FL médullaires, et soutenant un rôle des EVs dans la dissémination du FL et la résistance au traitement.Extracellular vesicles (EVs) are membrane-derived vesicles originating from multiple cellular pathways and exhibiting diverse content and nature. EVs are endowed with protumoral activities such as metabolism modification, immune escape, metastasis, and microenvironment reprogramming. Recent studies have shown that EVs contribute to the polarisation of tumor-infiltrating fibroblasts into pro-tumor supportive cells. This has been reported in particular in lymphoid malignancies developing within bone marrow (BM), such as multiple myeloma and chronic lymphocytic leukaemia. Follicular lymphoma is the most common indolent B-cell lymphoma, developing as a disseminated disease infiltrating lymph nodes (LN) and bone marrow (BM). This B-cell malignancy is strongly dependent on a germinal center-like permissive microenvironment exhibiting FL-specific features and driving the FL-supportive niche. Accordingly, the FL BM niche is characterized by an ectopic differentiation of lymphoid-like stromal cells and a local enrichment in CD4+ T cells, both reminiscent of LN follicular organization. However, the early driver mechanisms triggering the formation of this medullar FL permissive niche has not been yet identified. In the current work, we report that FL B cells produce EVs that could be internalized by BM mesenchymal stromal cells (BM-MSC), making them more efficient to support FL B-cell survival. Moreover, this supportive phenotype is different from that obtained under TNF/LT stimulation, the main driver of lymphoid stroma differentiation, and includes a strong upregulation of genes previously involved in the hematopoietic stem cell niche. Finally, BM-MSC priming by FL-derived EVs contribute to the selection of FL B cells with a quiescent phenotype mimicking those of BM FL B cells, supporting a role of EVs in FL dissemination and drug resistance

Étude du phénotype et de l'expression des miARNs chez les patients présentant une greffe combinée rein-foie

Introduction : Les études animales et cliniques suggèrent que, lors d'une greffe combinée rein-foie, l'allogreffe hépatique protégerait la greffe rénale des phénomènes de rejets. Nous avons comparé le phénotype sanguin et les profils d'expression des miARNs de patients présentant une greffe combinée rein-foie (CLK) avec des patients simples transplantés foie (L-STA) ou rein (K-STA). Pour évaluer l'effet positif de la greffe combinée, les profils d'expression des miARNs des CLK ont été comparés avec ceux de patients tolérants transplantés foie (L-TOL) ou rein (K-TOL). Méthode : Nous avons effectué un phénotypage exhaustif des CMSP en cytométrie en flux et un profilage de l'expression des miRNAs grâce à la technologie TLDA. Toutes les différences d'expression des miARNs ont été confirmées par PCR TaqMan individuelles sur une cohorte indépendante. Résultats : Les CLK présentent plus de B mémoires CD19+CD24+CD38Low que les L-STA et plus de Treg CD3+CD4+CD25HighCD127LowFOXP3+Helios+ que les K-STA. Par ailleurs, le phénotype sanguin des CLK diffère de celui des patients tolérants L-TOL et K-TOL. Au niveau moléculaire les CLK expriment un profil miARN mixte influencé par les deux greffons et n'ayant rien de commun avec les profils miARN observés chez les patients L-TOL et K-TOL. Ceci se traduit par la mise en place de réseaux de gènes différents entre les patients CLK, L-TOL et K-TOL. Conclusion : L'influence de la greffe combinée engendre un phénotype sanguin et un profil miRNA à mi-chemin entre L-STA et K-STA, non partagé par les patients tolérants.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

International audienceB-cell non-Hodgkin lymphoma (B-NHL) evolution and treatment are complicated by a high prevalence of relapses primarily due to the ability of malignant B cells to interact with tumor-supportive lymph node (LN) and bone marrow (BM) microenvironments. In particular, progressive alterations of BM stromal cells sustain the survival, proliferation, and drug resistance of tumor B cells during diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The current review describes how the crosstalk between BM stromal cells and lymphoma tumor cells triggers the establishment of the tumor supportive niche. DLBCL, FL, and CLL display distinct patterns of BM involvement, but in each case tumor-infiltrating stromal cells, corresponding to cancer-associated fibroblasts, exhibit specific phenotypic and functional features promoting the recruitment, adhesion, and survival of tumor cells. Tumor cell-derived extracellular vesicles have been recently proposed as playing a central role in triggering initial induction of tumor-supportive niches, notably within the BM. Finally, the disruption of the BM stroma reprogramming emerges as a promising therapeutic option in B-cell lymphomas. Targeting the crosstalk between BM stromal cells and malignant B cells, either through the inhibition of stroma-derived B-cell growth factors or through the mobilization of clonal B cells outside their supportive BM niche, should in particular be further evaluated as a way to avoid relapses by abrogating resistance niches

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center.

Management of pregnant women at high risk of pre-eclampsia (PE) requires frequent monitoring, with referral to specialized perinatal care centers. Reliable tests are necessary to improve prediction of PE and related complications and to assess disease severity and progression. An imbalance in two biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE. An elevated ratio is highly predictive of PE, whereas the diagnosis of PE can be ruled out within one week for low ratios. The main objective of this study was to assess whether a low sFlt-1/PlGF ratio, below a cutoff of 38, can predict the absence of PE within one week.We performed a prospective, monocentric, observational study to evaluate serum sFlt-1/PlGF ratio (Roche Diagnostics Cobas e411 system) for predicting -PE in a group of 67 high-risk pregnant women (20-37 gestation weeks).Among the 67 patients included, 53 had a sFlt-1/PlGF ratio lower than 38; none developed subsequent PE leading to a negative predictive value of 100%. Eight patients developed clinical PE. The positive predictive value was 21% at one week and 18% at four weeks, in accordance with previous studies.The serum sFlt-1/PlGF ratio showed highly predictive performances for ruling out PE. Using these biomarkers in routine management of PE may improve clinical care and avoid inappropriate hospitalization, which has a significant economic impact

Phenotypic and proteomic analysis of plasma extracellular vesicles highlights them as potential biomarkers of primary Sjogren syndrome

International audienceSjogren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS

CANPA: Computer-Assisted Natural Products Anticipation

Traditional natural products discovery workflows implying a combination of different targeting strategies including structure- and/or bioactivity-based approaches, afford no information about new compound structure until late in the discovery pipeline. By integrating a MS/MS prediction module and a collaborative library of (bio)chemical transformations, we have developed a new platform, coined MetWork, that is able of anticipating the structural identity of metabolites starting from any identified compound. In our quest to discover new monoterpene indole alkaloids, we demonstrate the utility of the MetWork platform by anticipating the structures of five previously undescribed sarpagine-like N-oxide alkaloids that have been targeted and isolated from the leaves of Alstonia balansae using a molecular networking-based dereplication strategy fueled by computer-generated annotations. This study constitutes the first example of non peptidic molecular networking-based natural product discovery workflow, in which the targeted structures were initially generated, and therefore anticipated by a computer prior to their isolation.</p

Effects of different amosite preparations on macrophages, lung damages, and autoimmunity

International audienceThe underlying mechanisms of asbestos-related autoimmunity are poorly understood. As the size, surface reactivity, and free radical activity of asbestos particles are considered crucial regarding the health effects, this study aims to compare the effects of exposure to pristine amosite (pAmo) or milled amosite (mAmo) particles on lung damage, autoimmunity, and macrophage phenotype. Four months after lung exposure to 0.1 mg of amosite, BAL levels of lactate dehydrogenase, protein, free DNA, CCL2, TGF-β1, TIMP-1, and immunoglobulin A of pAmo-exposed C57Bl/6 mice were increased when compared to fluids from control- and mAmo-exposed mice. Effects in pAmo-exposed mice were associated with lung fibrosis and autoimmunity including anti-double-strand DNA autoantibody production. mAmo or pAmo at 20 µg/cm(2) induced a pro-inflammatory phenotype characterized by a significant increase in TNFα and IL-6 secretion on human monocyte-derived macrophages (MDMs). mAmo and pAmo exposure induced a decrease in the efferocytosis capacities of MDMs, whereas macrophage abilities to phagocyte fluorescent beads were unchanged when compared to control MDMs. mAmo induced IL-6 secretion and reduced the percentage of MDMs expressing MHCII and CD86 markers involved in antigen and T-lymphocyte stimulation. By contrast, pAmo but not mAmo activated the NLRP3 inflammasome, as evaluated through quantification of caspase-1 activity and IL-1β secretion. Our results demonstrated that long-term exposure to pAmo may induce significant lung damage and autoimmune effects, probably through an alteration of macrophage phenotype, supporting in vivo the higher toxicity of entire amosite (pAmo) with respect to grinded amosite. However, considering their impact on efferocytosis and co-stimulation markers, mAmo effects should not be neglected. KEY MESSAGES: Lung fibrosis and autoimmunity induced by amosite particles depend on their physicochemical characteristics (size and surface) Inhalation exposure of mice to pristine amosite fibers is associated with lung fibrosis and autoimmunity Anti-dsDNA antibody is a marker of autoimmunity in mice exposed to pristine amosite fibers Activation of lung mucosa-associated lymphoid tissue, characterized by IgA production, after exposure to pristine amosite fibers Pristine and milled amosite particle exposure reduced the efferocytosis capacity of human-derived macrophages

Extracellular vesicles shed by follicular lymphoma B cells promote the polarization of bone marrow stromal cell niche

International audienceFollicular Lymphoma (FL) originates in the lymph nodes (LN) and infiltrates bone marrow (BM) early in the course of the disease. BM FL B cells are characterized by a lower cytological grade, a decreased proliferation, and a specific phenotypic and subclonal profile. Mesenchymal stromal cells (MSC) obtained from FL BM display a specific gene expression profile (GEP), including enrichment for a lymphoid-stromal cell signature, and an increased capacity to sustain FL B-cell growth. However, the mechanisms triggering the formation of the medullar FL permissive stromal niche have not been yet identified. In the current work, we demonstrated that FL B cells produced extracellular vesicles (EVs) that could be internalized by BM-MSC, making them more efficient to support FL B-cell survival and quiescence. Accordingly, EVs purified from FL BM plasma activated TGF-b dependent and independent pathways in BM-MSC, modified their GEP, triggering an upregulation of factors classically associated with hematopoietic stem cell niche, including CXCL12 or angiopoietin-1. Moreover, we provided the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSC. This work identified FL-derived EVs as putative mediators of BM stroma polarization and supported further investigation of their clinical interest for targeting the crosstalk between BM-MSC and malignant B cells