2.2. Les maisons de la rue Bernard-du-Bois et le lotissement de la rue d’après les données archéologiques

La fouille des niveaux modernes était « hors prescriptions » au moment de la fouille du 53-63 rue Bernard-du-Bois, le travail archéologique qui a pu être réalisé traite donc seulement de leur dégagement et du relevé exhaustif des différents éléments (murs, caves, sols) sis sur l’emprise de la fouille. Trois unités d’habitation, situées dans l’alignement de la rue Bernard-du-Bois, associées pour deux d’entre elles à deux fonds de caves, et des structures liées à des activités artisanales ont é..

Altered sleep homeostasis in rev-erbα knockout mice

Study Objectives: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep.Methods: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline.Results: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1–4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain.Conclusions: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context

The nuclear receptor REV-ERBα regulates Fabp7 and modulates adult hippocampal neurogenesis

The function of the nuclear receptor Rev-erbα (Nr1d1) in the brain is, apart from its role in the circadian clock mechanism, unknown. Therefore, we compared gene expression profiles in the brain between wild-type and Rev-erbα knock-out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a direct target of repression by REV-ERBα. Loss of Rev-erbα manifested in memory and mood related behavioral phenotypes and led to overexpression of Fabp7 in various brain areas including the subgranular zone (SGZ) of the hippocampus, where neuronal progenitor cells (NPCs) can initiate adult neurogenesis. We found increased proliferation of hippocampal neurons and loss of its diurnal pattern in Rev-erbα KO mice. In vitro, proliferation and migration of glioblastoma cells were affected by manipulating either Fabp7 expression or REV-ERBα activity. These results suggest an important role of Rev-erbα and Fabp7 in adult neurogenesis, which may open new avenues for treatment of gliomas as well as neurological diseases such as depression and Alzheimer

Aux portes de la Ville

Le projet d’aménagement et de réhabilitation immobilière de la colline Saint-Charles à Marseille, conduit par l’établissement public Euro­mé­diterranée, a donné lieu à une série de fouilles préventives menées par l’Inrap et la Ville de Marseille de 2002 à 2008. La colline est localisée dans un secteur potentiellement sensible du point de vue archéologique, en raison de sa proximité avec les portes principales de la cité antique et médiévale — ce qui laissait augurer des découvertes. Les fouilles ont livré les restes d’une manufacture royale des Poudres et Salpêtre, puis passée sous tutelle de l’État, édifiée au XVIIe siècle et en usage jusqu’au début du XXe siècle, les traces de vignobles grecs antiques, et les vestiges d’une occupation préhistorique courant du VIIIe millénaire au IVe millénaire av. J.-C. Cet ouvrage, accompagné d’une illustration abondante et souvent inédite, est consacré à la salpêtrière et à son environnement urbain. Il est le fruit d’une collaboration étroite entre archéologues et historiens, qui permet d’offrir une première synthèse sur le quartier de la Porte d’Aix de la fin du XVIIIe siècle à la première moitié du XIXe siècle avant que ce quartier ne se paupérise. Installée à l’entrée de la ville près de la Porte d’Aix au lieu-dit Bernard-du-Bois, ou du Bosc, la salpêtrière a disparu très tôt de la mémoire marseillaise. Les études qui lui sont consacrées ici mettent en lumière son évolution, de sa construction à la fin du XIXe siècle, et l’étonnante aventure de ses productions et des inventions qui y étaient associées, ainsi que sa complémentarité avec la poudrerie de Saint-Chamas. Elles permettent de documenter la genèse de l’îlot Bernard-du-Bois dans lequel elle a été implantée et qui — progressivement loti à partir de 1666, au moment de l’agrandissement de Marseille — accueillait à la fois maisons particulières et fabriques à l’origine de sa réputation artisanale. Elles montrent les liens que ces activités manufacturières ont pu entretenir avec celles du vallon voisin de la Joliette et le rôle de la salpêtrière dans leur implantation. La localisation d’industries nauséabondes ou potentiellement dangereuses dans l’enceinte de la ville a été également l’occasion de décrire le rapport des Marseillais à la pollution à partir de la fin du XVIIIe siècle, moment où la sensibilité liée aux odeurs évolue, et de documenter la manière dont la cité phocéenne avait lutté contre ce fléau. Ce quartier, aux portes de la ville, se présentait aussi comme un témoin idéal pour évoquer un pan peu exploré de la géographie et de l’histoire urbaine de Marseille : celle de la constitution de ses faubourgs et la question des limites et de l’entrée de ville. Les archéologues ont levé un lièvre, les historiens l’ont poursuivi. Cette collaboration étroite a permis d’aboutir à un travail qui, nous l’espérons, intéressera les acteurs des deux disciplines, ainsi qu’un lectorat désireux de mieux connaître l’histoire de la cité marseillaise. Nous formons également le souhait d’avoir contribué à la promotion de l’archéologie de la période moderne préindustrielle en montrant par cet exemple qu’elle est promise à un grand avenir et encourage de belles collaborations

Cerebrospinal fluid neopterin as marker of the meningo-encephalitic stage of Trypanosoma brucei gambiense sleeping sickness.

BACKGROUND: Sleeping sickness, or human African trypanosomiasis (HAT), is a protozoan disease that affects rural communities in sub-Saharan Africa. Determination of the disease stage, essential for correct treatment, represents a key issue in the management of patients. In the present study we evaluated the potential of CXCL10, CXCL13, ICAM-1, VCAM-1, MMP-9, B2MG, neopterin and IgM to complement current methods for staging Trypanosoma brucei gambiense patients. METHODS AND FINDINGS: Five hundred and twelve T. b. gambiense HAT patients originated from Angola, Chad and the Democratic Republic of the Congo (D.R.C.). Their classification as stage 2 (S2) was based on the number of white blood cells (WBC) (>5/µL) or presence of parasites in the cerebrospinal fluid (CSF). The CSF concentration of the eight markers was first measured on a training cohort encompassing 100 patients (44 S1 and 56 S2). IgM and neopterin were the best in discriminating between the two stages of disease with 86.4% and 84.1% specificity respectively, at 100% sensitivity. When a validation cohort (412 patients) was tested, neopterin (14.3 nmol/L) correctly classified 88% of S1 and S2 patients, confirming its high staging power. On this second cohort, neopterin also predicted both the presence of parasites, and of neurological signs, with the same ability as IgM and WBC, the current reference for staging. CONCLUSIONS: This study has demonstrated that neopterin is an excellent biomarker for staging T. b. gambiense HAT patients. A rapid diagnostic test for detecting this metabolite in CSF could help in more accurate stage determination

Altered Sleep Homeostasis in Rev-erbα Knockout Mice

Abstract Study Objectives: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. Methods: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. Results: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. Conclusions: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. Significance Although circadian clock genes are named for their role in driving circadian rhythms in gene expression, physiology, and behavior, they can fulfill other important functions. The clock gene and transcriptional repressor REV-ERBα plays a role in pathways affecting metabolism and central nervous functioning. Using mice lacking the gene encoding REV-ERBα, Nr1d1, we could extend these finding to include the homeostatic regulation of sleep. Because the activity of REV-ERBα is modulated by cellular redox state, we propose that this molecule can sense and respond to the metabolic imbalance imposed at the neuronal level by periods of extended wakefulness. Recently developed synthetic drugs targeting REV-ERBα could thus be useful in the treatment of both the circadian and homeostatic aspects of sleep-wake related disorders

Age-dependent alterations in human PER2 levels after early morning blue light exposure

In our modern society, we are exposed to different artificial light sources that could potentially lead to disturbances of circadian rhythms and, hence, represent a risk for health and welfare. Investigating the acute impact of light on clock-gene expression may thus help us to better understand the mechanisms underlying disorders rooted in the circadian system. Here, we show an overall significant reduction in PER2 expression in oral mucosa with aging in the morning, noon, and afternoon. In the afternoon, 10 h after exposure to early morning blue light, PER2 was significantly elevated in the young compared to green light exposure and to older participants. Our findings demonstrate that human buccal samples are a valuable tool for studying clock-gene rhythms and the response of PER2 to light. Additionally, our results indicate that the influence of light on clock-gene expression in humans is altered with age

Period2 gene mutant mice show compromised insulin-mediated endothelial nitric oxide release and altered glucose homeostasis

Period2 (Per2) is an important component of the circadian clock. Mutation of this gene is associated with vascular endothelial dysfunction and altered glucose metabolism. The aim of this study is to further characterize whole body glucose homeostasis and endothelial nitric oxide (NO) production in response to insulin in the mPer2(Brdm1) mice. We show that mPer2(Brdm1) mice exhibit compromised insulin receptor activation and Akt signaling in various tissues including liver, fat, heart, and aortas with a tissue-specific heterogeneous diurnal pattern, and decreased insulin-stimulated NO release in the aortas in both active and inactive phases of the animals. As compared to wild type (WT) mice, the mPer2(Brdm1) mice reveal hyperinsulinemia, hypoglycemia with lower fasting hepatic glycogen content and glycogen synthase level, no difference in glucose tolerance and insulin tolerance. The mPer2(Brdm1) mice do not show increased predisposition to obesity either on normal chow or high fat diet compared to WT controls. Thus, mice with Per2 gene mutation show altered glucose homeostasis and compromised insulin-stimulated NO release, independently of obesity

Etude typologique et analyse du remplissage par traitement statistique des structures en creux du site néolithique final de Jonquière 1 à La Fare-les-Oliviers (Bouches-du-Rhône)

International audienceThe execution of an approximately 4000 m2 excavation at the site of Jonquière 1, in La Fare-les-Oliviers, enabled the discovery of an end of the Neolithic habitat site, along the right bank of the Arc river. It contains nearly one hundred hollow structures, one of which was used as burial. Their typological study and the analysis of the filling by statistical treatment (HCA, PCA, tests) made it possible to establish four classes of hollow structures on the site as well as significant links between the filling and these classes or site zoning.La réalisation d’une fouille d’environ 4000 m2 sur le site de Jonquière 1, à La Fare-les-Oliviers, a permis de mettre au jour, en bordure de la rive droite de l’Arc, un site d’habitat de la fin du Néolithique. Celui-ci comporte près d’une centaine de structures en creux, dont l’une a été utilisée comme sépulture.Leur étude typologique et l’analyse du remplissage par traitement statistique (CAH, ACP, tests) ont permis d’établir quatre classes de structures en creux sur le site ainsi que des liens significatifs entre le comblement et ces classes et entre le comblement et le zonage du site

Etude typologique et analyse du remplissage par traitement statistique des structures en creux du site néolithique final de Jonquière 1 à La Fare-les-Oliviers (Bouches-du-Rhône)

International audienceThe execution of an approximately 4000 m2 excavation at the site of Jonquière 1, in La Fare-les-Oliviers,enabled the discovery of an end of the Neolithic habitat site, along the right bank of the Arc river. It containsnearly one hundred hollow structures, one of which was used as burial. Their typological study and theanalysis of the filling by statistical treatment (HCA, PCA, tests) made it possible to establish four classes ofhollow structures on the site as well as significant links between the filling and these classes or site zoning.La réalisation d’une fouille d’environ 4000 m2 sur le site de Jonquière 1, à La Fare-les-Oliviers, a permisde mettre au jour, en bordure de la rive droite de l’Arc, un site d’habitat de la fin du Néolithique. Celui-cicomporte près d’une centaine de structures en creux, dont l’une a été utilisée comme sépulture.Leur étude typologique et l’analyse du remplissage par traitement statistique (CAH, ACP, tests) ontpermis d’établir quatre classes de structures en creux sur le site ainsi que des liens significatifs entre lecomblement et ces classes et entre le comblement et le zonage du site