Physiology of cerebral circulation

The brain is unable to store oxygen and glucose. Therefore, its source in nutrients depends wholly on the blood supply, i.e. the cerebral circulation. This article first describes the main structural features of this circulation, before reviewing the mechanisms underlying its different types of regulation. These mechanisms maintain blood flow despite systemic changes (hypercapnia, hypoxia, or changes in perfusion pressure and in haematocrit), and when the neuron metabolic demand increases. This latter type of regulation, also called neurovascular coupling, provides the basis for functional neuroimaging techniques which are briefly described. Lastly, examples of diseases associated with a disorder of the regulation of cerebral circulation are given.Le cerveau est incapable de faire des réserves en oxygène et glucose. Il dépend donc pour ces nutriments de l'apport sanguin c'est-à-dire de la circulation cérébrale. Cet article décrit les principales caractéristiques structurales de cette circulation, puis il fait le point sur les mécanismes des différents types de régulation de la perfusion sanguine cérébrale. Ces mécanismes assurent la circulation malgré des variations systémiques (hypercapnie, hypoxie, variation de pression de perfusion et de l'hématocrite) mais aussi lorsque la demande métabolique neuronale est augmentée. Ce dernier type de régulation ou couplage neurovasculaire est à la base de techniques utilisées en neuroimagerie fonctionnelle, qui sont brièvement explicitées. Enfin, des exemples de pathologies dans lesquelles la régulation de la circulation cérébrale est perturbée sont donnés

Cerebral blood flow and gravito-inertial environment

To understand the pathophysiology of G-induced loss of consciousness (G-LOC) and of space sickness, the cerebral blood flow (CBF) and oxidative status of cerebral tissue were determined in animals (rabbits and rhesus monkeys) exposed to longitudinal positive accelerations (+Gz) and parabolic flights. The acceleration studies showed that CBF remains stable when cephalic arterial pressures are lower than the lower limit of autoregulation, and that CBF autoregulation is probably not triggered by G-load. Furthermore, results showed that G-LOC is due to a cerebral ischaemia. A transient increase in CBF was recorded in rabbits at the onset of weightlessness. CBF returned to control level afterwards, suggesting that its regulatory mechanisms are still efficient under conditions of microgravity.Afin de comprendre la physiopathologie de la perte de conscience induite par les accélérations (PCIA) longitudinales positives (+Gz) et celle du mal de l'espace, le débit sanguin cérébral cortical (DSC) et le statut oxydatif du tissu cérébral ont été mesurés chez des animaux (lapins et macaques rhésus) exposés à des accélérations +Gz et à des vols paraboliques. Les expériences sur les accélérations ont montré que le DSC est maintenu pour des pressions artérielles céphaliques inférieures à la limite inférieure à l'autorégulation, et que l'autorégulation du DSC n'est probablement pas mise en jeu. D'autre part, les résultats démontrent que la PCIA est due à une ischémie cérébrale. Par ailleurs, pendant les premières secondes d'apesanteur, le DSC du lapin est augmenté. Il retourne ensuite à sa valeur témoin, suggérant que les mécanismes de régulation du débit sont toujours efficaces en microgravité

Net Art et autoproduction: Acteurs et enjeux de la recherche : reconnaissance, créativité et industries du numérique

Ce rapport de recherche, financée par le Labex ICCA, industries culturelles & création artistique, met en avant une triple analyse - l’autoproduction et les modes de production ; la création et la créativité ; le processusd’industrialisation de la créativité numérique et de la marchandisation des pratiques artistiques. Cette recherche exploratoire a permis de confirmer les enjeux majeurs de l’autoproduction du Netart : des modèles économiquesémergents, des modes de financement de l’art relayés par l’industrie numérique et la marchandisationde la créativité numérique, la mise à l’écart du Netart et des arts numériques de l’art contemporain,provoquant des initiatives expérimentales pour poursuivre les projets et le processus de reconnaissance

Temps dans le cycle de vie du document numérique (Le)

Intervention au colloque "Le numérique : impact sur le cycle de vie du document", organisé à l\u27université de Montréal par l\u27EBSI et l\u27ENSSIB du 13 au 15 octobre 2004. Cet article propose une modélisation capable de rendre compte des différentes dimensions temporelles portées par un document. Après la définition de la notion de document, nous introduisons trois univers : l\u27univers sociohistorique, l\u27espace documentaire et l\u27univers du discours. Chacun d\u27eux contient sa propre dimension temporelle

Análise ao Observador e ao Polígrafo

As novas possibilidades do mundo conectado abriram brechas para os fenómenos político-culturais de pós-verdade, factos alternativos e de massificação de conteúdos falsos. Todas estas manifestações colocaram o jornalismo numa posição de fragilidade, pedindo por novos projetos que reforcem a sua credibilidade, tal como a verificação de factos. A prática de fact-checking foi iniciada na década de 1990 com o cuidado de verificar e corrigir o discurso político. Da necessidade crescente de validar e reagrupar os fact-checkers criouse, em 2015, a International Fact Checking Network. Com o objetivo de perceber como é feita a verificação de factos em Portugal, esta dissertação procura, através de uma análise de conteúdo, perceber a evolução, origem e execução dos mecanismos de fact-checking, a partir dos fact-checks realizados pelo Observador e pelo Polígrafo, em 2019. Esta investigação permitiu observar que as parcerias e as iniciativas de verificação de factos têm aumentado, principalmente em períodos de campanha eleitoral. Foi igualmente constatado que estas produções são, essencialmente, motivadas pelo número de compartilhamento de informação e, principalmente, de desinformação nas redes sociais. Observa-se, desta forma, um afastamento da função inicial de análise de discurso político que foi desvirtuada para o combate às notícias falsas. Deste trabalho, ainda se conclui que, nem sempre os fact-checkers seguem os princípios estabelecidos pela rede global a qual pertencem, não existindo assim uma padronização da metodologia de verificação de factos.The new possibilities of the connected world have opened loopholes for political and cultural phenomena, such as alternative facts and the spread of fake news in a post-truth world. This situation putted the journalistic industry in an unsettled position, asking for new projects that could reinforce its credibility. The practice of fact-checking was initiated in the 1990s in order to check and correct the political propaganda and speech. From the growing need to validate and regroup fact-checkers, the International Fact Checking Network was founded in 2015. In order to understand how fact-checking is carried out in Portugal, this dissertation seeks to understand the origin, evolution and execution of fact-checking mechanisms, through a content analysis based on the fact-checks carried out by the Observador and the Polígrafo in 2019. This investigation made it possible to observe that fact-checking initiatives and partnerships have increased, especially during election campaign periods. It was also found that these productions are essentially motivated by the number of information and misinformation shared on social media. That way, it is possible to observe that fact-checking has distanced itself from the initial pupose to play and active role in fighting fake news. From this work, we also noticed that fact-checkers do not always follow the principles established by the International Network to which they belong. Therefore, it makes us presume that there is no standardization of the fact-checking methodology

Hydrogen bonding to the cysteine ligand of superoxide reductase: acid–base control of the reaction intermediates

International audienceSuperoxide reductase SOR is a non-heme iron metalloenzyme that detoxifies superoxide radical in microorganisms. Its active site consists of an unusual non-heme Fe2+ center in a [His4 Cys1] square pyramidal pentacoordination, with the axial cysteine ligand proposed to be an essential feature in catalysis. Two NH peptide groups from isoleucine 118 and histidine 119 establish H-bondings with the sulfur ligand (Desulfoarculus baarsii SOR numbering). In order to investigate the catalytic role of these H-bonds, the isoleucine 118 residue of the SOR from Desulfoarculus baarsii was mutated into alanine, aspartate or serine residues. Resonance Raman spectroscopy showed that the mutations specifically induced an increase of the strength of the Fe3+-S(Cys) and S-Cβ(Cys) bonds as well as a change in conformation of the cysteinyl side chain, which was associated with the alteration of the NH hydrogen bonding to the sulfur ligand. The effects of the isoleucine mutations on the reactivity of SOR with O2●- were investigated by pulse radiolysis. These studies showed that the mutations induced a specific increase of the pKa of the first reaction intermediate, recently proposed to be an Fe2+-O2●- species. These data were supported by DFT calculations carried out on three models of the Fe2+-O2●- intermediate, with one, two or no H-bonds on the sulfur ligand. Our results demonstrated that the hydrogen bonds between the NH (peptide) and the cysteine ligand tightly control the rate of protonation of the Fe2+-O2●- reaction intermediate to form an Fe3+-OOH species

Emerging Roles of ADAM and ADAMTS Metalloproteinases in Cancer

A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions

Proposal of a quantitative PCR-based protocol for an optimal Pseudomonas aeruginosa detection in patients with cystic fibrosis

BACKGROUND: The lung of patients with cystic fibrosis (CF) is particularly sensitive to Pseudomonas aeruginosa. This bacterium plays an important role in the poor outcome of CF patients. During the disease progress, first acquisition of P. aeruginosa is the key-step in the management of CF patients. Quantitative PCR (qPCR) offers an opportunity to detect earlier the first acquisition of P. aeruginosa by CF patients. Given the lack of a validated protocol, our goal was to find an optimal molecular protocol for detection of P. aeruginosa in CF patients. METHODS: We compared two formerly described qPCR formats in early detection of P. aeruginosa in CF sputum samples: a qPCR targeting oprL gene, and a multiplex PCR targeting gyrB and ecfX genes. RESULTS: Tested in vitro on a large panel of P. aeruginosa isolates and others gram-negative bacilli, oprL qPCR exhibited a better sensitivity (threshold of 10 CFU/mL versus 730 CFU/mL), whereas the gyrB/ecfX qPCR exhibited a better specificity (90% versus 73%). These results were validated ex vivo on 46 CF sputum samples positive for P. aeruginosa in culture. Ex vivo assays revealed that qPCR detected 100 times more bacterial cells than culture-based method did. CONCLUSION: Based on these results, we proposed a reference molecular protocol combining the two qPCRs, which offers a sensitivity of 100% with a threshold of 10 CFU/mL and a specificity of 100%. This combined qPCR-based protocol can be adapted and used for other future prospective studies