Prospective des villes en 2010

La tendance à la métropolisation, c'est-à-dire la concentration des hommes et des activités les plus dynamiques dans les grandes villes, et le déclin corrélatif des petites villes et des zones rurales doivent-ils et peuvent-ils être infléchis par une politique d'aménagement du territoire ? Les experts interrogés révèlent un grand décalage entre le souhaité et le probable. La recherche de l'équilibre du territoire et de la qualité de vie s'oppose à la logique de croissance économique qui renforce les zones les plus dynamiques. Quelles interventions faut-il alors privilégier ? Une première mesure d'équité serait une meilleure affectation des coûts et des charges de telle sorte que chaque agent économique et chaque partie du territoire supporte bien les dépenses qu'ils engendrent. Mais, l'utilisation des leviers économiques, tarification et action sur les prix, est considérée peu efficace et non souhaitable. Les mesures incitatives et positives, notamment en matière d'infrastructures de transports et relatives aux métropoles et aux villes moyennes, sont préférées à des mesures restrictives ou limitatives, même si celles-ci concernent la région parisienne. En fait, les experts semblent ne pas oser se prononcer sur le caractère souhaitable et efficace à long terme des interventions restrictives et, dans le doute, ils préfèrent maintenir le statu quo.politique urbaine ; aménagement du territoire ; agglomérations urbaines ; prospective ; méthode Delphi ; France

NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model.

While the spatiotemporal development of Tau pathology has been correlated with occurrence of cognitive deficits in Alzheimer's patients, mechanisms underlying these deficits remain unclear. Both brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB play a critical role in hippocampus-dependent synaptic plasticity and memory. When applied on hippocampal slices, BDNF is able to enhance AMPA receptor-dependent hippocampal basal synaptic transmission through a mechanism involving TrkB and N-methyl-d-Aspartate receptors (NMDAR). Using THY-Tau22 transgenic mice, we demonstrated that hippocampal Tau pathology is associated with loss of synaptic enhancement normally induced by exogenous BDNF. This defective response was concomitant to significant memory impairments. We show here that loss of BDNF response was due to impaired NMDAR function. Indeed, we observed a significant reduction of NMDA-induced field excitatory postsynaptic potential depression in the hippocampus of Tau mice together with a reduced phosphorylation of NR2B at the Y1472, known to be critical for NMDAR function. Interestingly, we found that both NR2B and Src, one of the NR2B main kinases, interact with Tau and are mislocalized to the insoluble protein fraction rich in pathological Tau species. Defective response to BDNF was thus likely related to abnormal interaction of Src and NR2B with Tau in THY-Tau22 animals. These are the first data demonstrating a relationship between Tau pathology and synaptic effects of BDNF and supporting a contribution of defective BDNF response and impaired NMDAR function to the cognitive deficits associated with Tauopathies

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.

International audienceThe genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered γ-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

Rectal Carriage of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacilli in Community Settings in Madagascar

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteria (ESBL-PE) emerged at the end of the 1980s, causing nosocomial outbreaks and/or hyperendemic situations in hospitals and long-term care facilities. In recent years, community-acquired infections due to ESBL-PE have spread worldwide, especially across developing countries including Madagascar. OBJECTIVES: This study aimed to determine the prevalence and risk factors of intestinal carriage of ESBL-PE in the community of Antananarivo. METHODS: Non-hospitalized patients were recruited in three health centers in different socio economic settings. Fresh stool collected were immediately plated on Drigalski agar containing 3 mg/liter of ceftriaxone. Gram-negative bacilli species were identified and ESBL production was tested by a double disk diffusion (cefotaxime and ceftazidime +/- clavulanate) assay. Characterization of ESBLs were perfomed by PCR and direct sequencing . Molecular epidemiology was analysed by Rep-PCR and ERIC-PCR. RESULTS: 484 patients were screened (sex ratio  = 1.03, median age 28 years). 53 ESBL-PE were isolated from 49 patients (carrier rate 10.1%). The isolates included Escherichia coli (31), Klebsiella pneumoniae (14), Enterobacter cloacae (3), Citrobacter freundii (3), Kluyvera spp. (1) and Pantoae sp.(1). In multivariate analysis, only the socioeconomic status of the head of household was independently associated with ESBL-PE carriage, poverty being the predominant risk factor. CONCLUSIONS: The prevalence of carriage of ESBL in the community of Antananarivo is one of the highest reported worldwide. This alarming spread of resistance genes should be stopped urgently by improving hygiene and streamlining the distribution and consumption of antibiotics

Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.

Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen HeCo mice display this phenotype, and our study revealed that misplaced apical progenitors contribute to heterotopia formation. While HeCo neurons migrated at the same speed as wild type, abnormally distributed dividing progenitors were found throughout the cortical wall from embryonic day 13. We identified Eml1, encoding a microtubule-associated protein, as the gene mutated in HeCo mice. Full-length transcripts were lacking as a result of a retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo progenitor phenotype and reexpression rescued it. We further found EML1 to be mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human

Long-Term Vegetation Change in Central Africa: The Need for an Integrated Management Framework for Forests and Savannas

peer reviewedTropical forests and savannas are the main biomes in sub-Saharan Africa, covering most of the continent. Collectively they offer important habitat for biodiversity and provide multiple ecosystem services. Considering their global importance and the multiple sustainability challenges they face in the era of the Anthropocene, this chapter undertakes a comprehensive analysis of the past, present, and future vegetation patterns in central African forests and savannas. Past changes in climate, vegetation, land use, and human activity have affected the distribution of forests and savannas across central Africa. Currently, forests form a continuous block across the wet and moist areas of central Africa, and are characterized by high tree cover (>90% tree cover). Savannas and woodlands have lower tree cover (<40% tree cover), are found in drier sites in the north and south of the region, and are maintained by frequent fires. Recent tree cover loss (2000–2015) has been more important for forests than for savannas, which, however, reportedly experienced woody encroachment. Future cropland expansion is expected to have a strong impact on savannas, while the extent of climatic impacts depends on the actual scenario. We finally identify some of the policy implications for restoring ecosystems, expanding protected areas, and designing sustainable ecosystem management approaches in the region

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Les flûtes paléolithiques d'Isturitz (Pyrénées-Atlantiques)

RESUME La grotte d'isturitz (Pyrénées-Atlantiques) a été fouillée entre 1912 et 1922 par E. Passemard. De 1928 à 1950, R. et S. de Saint-Périer y ont repris des fouilles qui ont été menées jusqu'en 1954 par S. de Saint-Périer après la mort de son mari. Ils ont découvert d'importantes couches archéologiques attribuées au Paléolithique moyen (Moustérien) et supérieur (Aurignacien, Gravettien, Solutréen, Magdalénien moyen et supérieur, Azilien). La collection d'isturitz conservée au Musée des Antiquités Nationales compte une série unique d'os d'oiseaux portant une ou plusieurs perforations, parfois ornés, que nous pouvons interpréter comme des fragments de flûtes. La plupart de ces objets proviennent de la couche gravettienne. Les raccords de plusieurs fragments nous ont permis de reconstituer une flûte à quatre trous ; la plus longue connue à ce jour datant du Paléolithique. L'intérêt de cette étude est aussi de proposer différents modèles théoriques que nous expérimenterons ultérieurement. La grotte d'isturitz correspond à l'étage supérieur d'un vaste réseau karstique qui s'étend sur les communes d'isturitz et de Saint-Martin-d'Arberoue (Pyrénées- Atlantiques). Longue d'environ 120 m, large de 50 m, pour une hauteur atteignant parfois 20 m, cette cavité est divisée en deux grandes salles d'orientation parallèle. L'une, appelée Salle Sud ou Salle de Saint-Martin, débouche au Sud sur la commune de Saint-Martin, l'autre nommée Salle Nord, d'isturitz ou Grande Salle, s'ouvre au Nord sur la commune d'isturitz.Buisson Dominique. Les flûtes paléolithiques d'Isturitz (Pyrénées-Atlantiques). In: Bulletin de la Société préhistorique française, tome 87, n°10-12, 1990. Spécial bilan de l'année de l'archéologie. pp. 420-433

Façonnage et gravures sur des os humains d'Isturitz (Pyrénées-Atlantiques)

Buisson D., Gambier Dominique. Façonnage et gravures sur des os humains d'Isturitz (Pyrénées-Atlantiques). In: Bulletin de la Société préhistorique française, tome 88, n°6, 1991. pp. 172-177