Solidarités environnementales, contestation transnationale et renouvellement de la politique mondiale

L’ordre politique de la mondialisation est un champ conflictuel de relations économiques, culturelles et sociales au sein duquel les mouvements sociaux transnationaux construisent une nouvelle politique située au-delà des institutions traditionnelles. Cet article vise à proposer un cadre d´analyse théorique illustré à partir de la contribution d´un mouvement reconnu sur la scène internationale qui a réussi à mener une action politique transnationale dans le champ de l´environnementalisme. Dans ce cadre, les auteurs soulignent la convergence de six catégories d’analyse de l´action collective mise en oeuvre par les mouvements de protection de l´environnement. Les six catégories suggérées (statut de compétence, articulation des échelles, temporalité, multiplicité des identités et des représentations, structure organisationnelle, visibilité) mettent en relief le besoin de reconsidérer le sens hégémonique de la politique mondiale fondée exclusivement sur le marché et les négociations interétatiques.Globalization is a political order creating new fields of economic, cultural and social conflicts, wherein transnational social movements reaffirm a new politics beyond the conventional institutions. This article proposes an analytical framework, illustrated by the history of a well studied environmental movement. The authors present a set of six converging analytical categories stemming from the study of environmental movements. These categories (political competence, scale, temporality, multiple identities/representations, organisational structure, visibility) emphasise the need to question the current hegemonic understanding of world politics that has been almost always exclusively rooted in global markets and inter-state negotiations

ESPAÇO MUNDIAL E ORDEM POLÍTICA CONTEMPORÂNEA: uma agenda de pesquisa para um novo sentido da internacionalização

Este artigo responde a um duplo desafio. Em primeiro lugar, o de assumir a necessidade de ampliar os discursos vigentes sobre o espaço mundial, contornando visões despolitizadoras da política internacional. Em segundo lugar, o de renovar o sentido da internacionalização, no âmbito de um campo interdisciplinar, analisando as relações internacionais como sistema-mundo e integrando temas relativos à desigualdade e diferença, ao gênero, à justiça social, ao desenvolvimento e ao meio ambiente no plano da política mundial – aqui considerada como o conjunto das relações sociais que atravessam as fronteiras nacionais e que se estabelecem entre as diversas sociedades. Para tanto, são sugeridos três eixos analíticos em torno dos quais é apresentada uma proposta de agenda de pesquisas sobre a ordem política contemporânea: a) os ideários, valores e conteúdos de referência na política mundial; b) o sistema-mundo e as relações transnacionais; c) a influência da ação dos sujeitos na redefinição de um novo sentido para a internacionalização da política. PALAVRAS-CHAVE: espaço mundial, política contemporânea, teoria das relações internacionais, transnacionalismos.THE WORLD SPACE AND THE CONTEMPORARY POLITICAL ORDER: a research agenda aiming at a renewed approach to international politics Carlos R. S. Milani Ruthy Nadia Laniado This paper proposes a twofold challenge with respect to theorizing international politics. Firstly, it suggests that it is quite important to enlarge the existing discourses about the world space and, concurrently, to by-pass the consolidated de-politicized approaches to international politics. Secondly, the paper aims at renewing the meaning of internationalization focusing on interdisciplinary approaches and the idea of international relations as a worldsystem. Therefore it is necessary to embrace issues related to inequality, difference, gender, social justice, development and environment at the level of world politics, herein defined as the ensemble of social relations that transpose national frontiers and establish themselves among the most diverse societies. Hence, three analytical axes are proposed for a research agenda about the contemporary political order: a) ideals, values and referring contents of world politics; b) world-system and transnational relations; c) the influence of acting subjects in redefining a new meaning for the internationalization of politics. KEY WORD: world space, contemporary politics, international relations theory, transnationalisms.ESPACE MONDIAL ET ORDRE POLITIQUE CONTEMPORAIN: un agenda de recherche en vue d´un nouveau sens de l´international Carlos R. S. Milani Ruthy Nadia Laniado Cet article relève d´un double défi. En premier lieu, tenir compte du besoin d´ouverture des discours en vogue sur l´espace mondial et dans le même temps, éviter les visions dépolitisées de la politique internationale. En deuxième lieu, renouveler le sens de l´international, dans le cadre d´un champ interdisciplinaire, en analysant les relations internationales comme un système-monde et en intégrant des thématiques relatives à l´inégalité et la différence, aux rapports entre les sexes hommes-femmes (genre), à la justice sociale, au développement et à l´environnement sur le plan de la politique mondiale – laquelle est ici définie comme l´ensemble des relations sociales au-delà des frontières nationales et à travers les différentes sociétés. C´est ainsi que les auteurs de cet article suggèrent trois axes d´analyse autour desquels ils proposent un agenda de recherche sur l´ordre politique contemporain: a) les idées, les valeurs et les contenus de référence dans la politique mondiale; b) le système-monde et les relations transnationales; c) l´influence de l´action des sujets dans la redéfinition d´un nouveau sens de la internationalisation du politique. MOTS CLÉS:espace mondial, politique contemporaine, théorie des relations internationales, transnationalismes.Publicação Online do Caderno CRH:http://www.cadernocrh.ufba.b

A Novel t(8;14)(q24;q11) Rearranged Human Cell Line as a Model for Mechanistic and Drug Discovery Studies of NOTCH1-Independent Human T-Cell Leukemia

MYC-translocated T-lineage acute lymphoblastic leukemia (T-ALL) is a rare subgroup of T-ALL associated with CDKN2A/B deletions, PTEN inactivation, and absence of NOTCH1 or FBXW7 mutations. This subtype of T-ALL has been associated with induction failure and aggressive disease. Identification of drug targets and mechanistic insights for this disease are still limited. Here, we established a human NOTCH1-independent MYC-translocated T-ALL cell line that maintains the genetic and phenotypic characteristics of the parental leukemic clone at diagnosis. The University of Padua T-cell acute lymphoblastic leukemia 13 (UP-ALL13) cell line has all the main features of the above described MYC-translocated T-ALL. Interestingly, UP-ALL13 was found to harbor a heterozygous R882H DNMT3A mutation typically found in myeloid leukemia. Chromatin immunoprecipitation coupled with high-throughput sequencing for histone H3 lysine 27 (H3K27) acetylation revealed numerous putative super-enhancers near key transcription factors, including MYC, MYB, and LEF1. Marked cytotoxicity was found following bromodomain-containing protein 4 (BRD4) inhibition with AZD5153, suggesting a strict dependency of this particular subtype of T-ALL on the activity of super-enhancers. Altogether, this cell line may be a useful model system for dissecting the signaling pathways implicated in NOTCH1-independent T-ALL and for the screening of targeted anti-leukemia agents specific for this T-ALL subgroup

Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism

Immunometabolism investigates the intricate relationship between the immune system and cellular metabolism. This study delves into the consequences of mitochondrial frataxin (FXN) depletion, the primary cause of Friedreich's ataxia (FRDA), a debilitating neurodegenerative condition characterized by impaired coordination and muscle control. By using single-cell RNA sequencing, we have identified distinct cellular clusters within the cerebellum of an FRDA mouse model, emphasizing a significant loss in the homeostatic response of microglial cells lacking FXN. Remarkably, these microglia deficient in FXN display heightened reactive responses to inflammatory stimuli. Furthermore, our metabolomic analyses reveal a shift towards glycolysis and itaconate production in these cells. Remarkably, treatment with butyrate counteracts these immunometabolic changes, triggering an antioxidant response via the itaconate-Nrf2-GSH pathways and suppressing the expression of inflammatory genes. Furthermore, we identify Hcar2 (GPR109A) as a mediator involved in restoring the homeostasis of microglia without FXN. Motor function tests conducted on FRDA mice underscore the neuroprotective attributes of butyrate supplementation, enhancing neuromotor performance. In conclusion, our findings elucidate the role of disrupted homeostatic function in cerebellar microglia in the pathogenesis of FRDA. Moreover, they underscore the potential of butyrate to mitigate inflammatory gene expression, correct metabolic imbalances, and improve neuromotor capabilities in FRDA

Lack of CC chemokine ligand 2 differentially affects inflammation and fibrosis according to the genetic background in a murine model of steatohepatitis

Expression of CCL2 (CC chemokine ligand 2) (or monocyte chemoattractant protein-1) regulates inflammatory cell infiltration in the liver and adipose tissue, favouring steatosis. However, its role in the pathogenesis of steatohepatitis is still uncertain. In the present study, we investigated the development of non-alcoholic steatohepatitis induced by an MCD diet (methionine/choline-deficient diet) in mice lacking the CCL2 gene on two different genetic backgrounds, namely Balb/C and C57/Bl6J. WT (wild-type) and CCL2-KO (knockout) mice were fed on a lipid-enriched MCD diet or a control diet for 8 weeks. In Balb/C mice fed on the MCD diet, a lack of CCL2 was associated with lower ALT (alanine transaminase) levels and reduced infiltration of inflammatory cells, together with a lower generation of oxidative-stress-related products. Sirius Red staining demonstrated pericellular fibrosis in zone 3, and image analysis showed a significantly lower matrix accumulation in CCL2-KO mice. This was associated with reduced hepatic expression of TGF-β (transforming growth factor-β), type I procollagen, TIMP-1 (tissue inhibitor of metalloproteinases-1) and α-smooth muscle actin. In contrast, in mice on a C57Bl/6 background, neither ALT levels nor inflammation or fibrosis were significantly different comparing WT and CCL2-KO animals fed on an MCD diet. In agreement, genes related to fibrogenesis were expressed to comparable levels in the two groups of animals. Comparison of the expression of several genes involved in inflammation and repair demonstrated that IL (interleukin)-4 and the M2 marker MGL-1 (macrophage galactose-type C-type lectin 1) were differentially expressed in Balb/C and C57Bl/6 mice. No significant differences in the degree of steatosis were observed in all groups of mice fed on the MCD diet. We conclude that, in experimental murine steatohepatitis, the effects of CCL2 deficiency are markedly dependent on the genetic background

Optimizing fluid management in patients with acute decompensated heart failure (ADHF): the emerging role of combined measurement of body hydration status and brain natriuretic peptide (BNP) levels

The study tests the hypothesis that in patients admitted with acutely decompensated heart failure (ADHF), achievement of adequate body hydration status with intensive medical therapy, modulated by combined bioelectrical vectorial impedance analysis (BIVA) and B-type natriuretic peptide (BNP) measurement, may contribute to optimize the timing of patient’s discharge and to improve clinical outcomes. Three hundred patients admitted for ADHF underwent serial BIVA and BNP measurement. Therapy was titrated to reach a BNP value of <250 pg/ml, whenever possible. Patients were categorized as early responders (rapid BNP fall below 250 pg/ml); late responders (slow BNP fall below 250 pg/ml, after aggressive therapy); and non-responders (BNP persistently >250 pg/ml). Worsening of renal function (WRF) was evaluated during hospitalization. Death and rehospitalization were monitored with a 6-month follow-up. BNP value on discharge of ≤250 pg/ml led to a 25% event rate within 6 months (Group A: 17.4%; Group B: 21%, Chi2; n.s.), whereas a value >250 pg/ml (Group C) was associated with a far higher percentage (37%). At discharge, body hydration was 73.8 ± 3.2% in the total population and 73.2 ± 2.1, 73.5 ± 2.8, 74.1 ± 3.6% in the three groups, respectively. WRF was observed in 22.3% of the total. WRF occurred in 22% in Group A, 32% in Group B, and 20% in Group C (P = n.s.). Our study confirms the hypothesis that combined BNP/BIVA sequential measurements help to achieve adequate fluid balance status in patients with ADHF and can be used to drive a “tailored therapy,” allowing clinicians to identify high-risk patients and possibly to reduce the incidence of complications secondary to fluid management strategies

Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p

Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p