REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia

The hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia which promotes oxygen delivery and metabolic adaptation to oxygen deprivation. However, the degree and duration of HIF-1α expression in hypoxia must be carefully balanced within cells in order to avoid unwanted side effects associated with excessive activity. The expression of HIF-1α mRNA is suppressed in prolonged hypoxia, suggesting that the control of HIF1A gene transcription is tightly regulated by negative feedback mechanisms. Little is known about the resolution of the HIF-1α protein response and the suppression of HIF-1α mRNA in prolonged hypoxia. Here, we demonstrate that the Repressor Element 1-Silencing Transcription factor (REST) binds to the HIF-1α promoter in a hypoxia-dependent manner. Knockdown of REST using RNAi increases the expression of HIF-1α mRNA, protein and transcriptional activity. Furthermore REST knockdown increases glucose consumption and lactate production in a HIF-1α- (but not HIF-2α-) dependent manner. Finally, REST promotes the resolution of HIF-1α protein expression in prolonged hypoxia. In conclusion, we hypothesize that REST represses transcription of HIF-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1α response

Thrombospondin-2 and SPARC/osteonectin are critical regulators of bone remodeling

Thrombospondin-2 (TSP2) and osteonectin/BM-40/SPARC are matricellular proteins that are highly expressed by bone cells. Mice deficient in either of these proteins show phenotypic alterations in the skeleton, and these phenotypes are most pronounced under conditions of altered bone remodeling. For example, TSP2-null mice have higher cortical bone volume and are resistant to bone loss associated with ovariectomy, whereas SPARC-null mice have decreased trabecular bone volume and fail to demonstrate an increase in bone mineral density in response to a bone-anabolic parathyroid hormone treatment regimen. In vitro, marrow stromal cell (MSC) osteoprogenitors from TSP2-null mice have increased proliferation but delayed formation of mineralized matrix. Similarly, in cultures of SPARC-null MSCs, osteoblastic differentiation and mineralized matrix formation are decreased. Overall, both TSP2 and SPARC positively influence osteoblastic differentiation. Intriguingly, both of these matricellular proteins appear to impact MSC fate through mechanisms that could involve the Notch signaling system. This review provides an overview of the role of TSP2 and SPARC in regulating bone structure, function, and remodeling, as determined by both in vitro and in vivo studies

Architecture, symbolic capital and elite mobilizations: The case of the Royal Bank of Scotland corporate campus

In this article, we apply the conceptual framework of Pierre Bourdieu, in particular forms of capital, social fields, field of power and modes of domination, to demonstrate how the study of a symbolically powerful building can provide insights into what are often opaque elite interactions. In order to do this, we focus on the corporate campus headquarters of a powerful financial institution, the Royal Bank of Scotland in the context of Scotland in the period 2000–2009. We pose the following questions: What is the relationship between corporate space and the field of power? What role does a corporate building play in circuits of capital conversion? What does this case tell us about the role of architecture in elite mobilisations? In addressing these questions, we contribute to critical organisation studies by identifying and theorising the role of corporate space in inter-elite dynamics and circuits of capital conversion. This approach, we argue, provides a methodological lever which could be applied to other symbolically important buildings in order to understand the nature and role of inter-field interactions in the conception and realisation of such buildings

Proximidad espacial y distancia social. Los grandes conjuntos de vivienda social y su población

International audienceVersion espagnole publiée en 2020 d'un texte traduit d'un article de JC Chamboredon décédé en mai 2020 : Proximité spatiale et distance sociale. Les grands ensembles et leur peuplement, Revue française de sociologie Année 1970 11-1 pp. 3-3

Revisiting the role of hCG: new regulation of the angiogenic factorEG-VEGF and its receptor

International audienceEndocrine gland-derived vascular endothelialgrowth factor (EG-VEGF) is an angiogenic factor reportedto be specific for endocrine tissues, including the placenta.Its biological activity is mediated via two G proteincoupledreceptors, prokineticin receptor 1 (PROKR1) andprokineticin receptor 2 (PROKR2). We have recentlyshown that (i) EG-VEGF expression peaks between the 8thand 11th weeks of gestation, (ii) its mRNA and proteinlevels are up-regulated by hypoxia, (iii) EG-VEGF is anegative regulator of trophoblast invasion and (iv) its circulatinglevels are increased in preeclampsia (PE), the mostthreatening pathology of pregnancy. Here, we investigatedthe regulation of the expression of EG-VEGF and itsreceptors by hCG, a key pregnancy hormone that is alsoderegulated in PE. During the first trimester of pregnancy,hCG and EG-VEGF exhibit the same pattern of expression,suggesting that EG-VEGF is potentially regulated by hCG.Both placental explants (PEX) and primary cultures oftrophoblasts from the first trimester of pregnancy were usedto investigate this hypothesis. Our results show that(i) LHCGR, the hCG receptor, is expressed both in cytoandsyncytiotrophoblasts, (ii) hCG increases EG-VEGF,PROKR1 and PROKR2 mRNA and protein expression in adose- and time-dependent manner, (iii) hCG increases therelease of EG-VEGF from PEX conditioned media, (iv)hCG effects are transcriptional and post-transcriptional and(v) the hCG effects are mediated by cAMP via cAMPresponse elements present in the EG-VEGF promoterregion. Altogether, these results demonstrate a new role forhCG in the regulation of EG-VEGF and its receptors, anemerging regulatory system in placental developmen

Between young children and adults: practical logic in families’ lives

International audienc

A educação infantil e a questão da escola: o caso da França

Nos últimos trinta anos, a prioridade dada a uma lógica escolar para justificar a pré-escola coincide com uma dupla mudança na instituição. A primeira diz respeito às relações que a escola maternal mantém com a escolarização obrigatória e com as estruturas de cuidados para as crianças pequenas. A outra refere-se às reformas do currículo escolar e ao desenvolvimento dos processos de avaliação. A escola maternal, local de acolhimento, de cuidados e de preparação para a escola, tornou-se institucionalmente uma verdadeira escola. A difusão das comparações internacionais contribuiu para essas mudanças