The evaluation of retail centrality, understood as the retail potential of a location, is commonly associated with the binomial center-polarization and with the binomial accessibility-attractiveness. ...However, by reducing market logic too much to these elements, we may have missed something. Our consumption practices have evolved, particularly over the last twenty years: we are increasingly mobile, and consumption is part of an increasingly complex chain of journeys. But at the same time, when we do consume, there has never been a greater demand for proximity or home delivery. As a result, the retail offer is increasingly polymorphous, with the point of sale being just one of several means of reaching potential customers.The theory developed here by the author is that the primacy of the polarising market centrality is a thing of the past. There are as many modes of centrality as there are basic spatial forms: the point, the line, the area, the network. This article looks successively at the four modes of centrality thus constituted: polarising centrality, positioning centrality, anchoring centrality and distant centrality. The aim is to show how each mode of centrality has its own logic, interacts differently with the retail function, corresponds to different consumption behaviours, and generates specific retail forms and landscapes.
L’évaluation de la centralité marchande, entendue comme le potentiel marchand d’un lieu,va communément de pair avec le binôme centre-polarisation et avec le binôme accessibilité-attractivité. Pourtant, à trop réduire les logiques marchandes à ces éléments, nous sommes peut-être passé à côté de quelque chose.Ainsi, nos pratiques de consommation ont évolué notamment sur les vingt dernières années : nous sommes de plus en plus motiles et mobiles, et la consommation s’insère dans des chaînages de déplacements de plus en plus complexes. Mais en parallèle, lorsque nous consommons, le recours à la proximité ou à la livraison à domicile, n’ont jamais été autant sollicités. En conséquence l’offre marchande est de plus en plus polymorphe, le lieu de vente n’étant qu’un moyen parmi d’autres d’atteindre le client potentiel.La théorie développée ici par l’auteur est que le primat de la centralité marchande de polarisation est révolu. Il existerait autant de modes de centralité qu’il existe de formes spatiales de bases : le point, la ligne, l’aire, le réseau. Cet article propose d’aborder successivement les quatre modes de centralité ainsi constitués : la centralité de polarisation, la centralité de positionnement, la centralité d’ancrage, la centralité en distanciel. Il s’agit de voir en quoi chaque mode de centralité a ses propres logiques, interagit différemment avec la fonction marchande, correspond à des comportements de consommation différents, génère des formes et paysages marchands spécifiques.
Complex cortical malformations associated with mutations in tubulin genes: TUBA1A, TUBA8, TUBB2B, TUBB3, TUBB5 and TUBG1 commonly referred to as tubulinopathies, are a heterogeneous group of ...conditions with a wide spectrum of clinical severity. Among the 106 patients selected as having complex cortical malformations, 45 were found to carry mutations in TUBA1A (42.5%), 18 in TUBB2B (16.9%), 11 in TUBB3 (10.4%), three in TUBB5 (2.8%), and three in TUBG1 (2.8%). No mutations were identified in TUBA8. Systematic review of patients' neuroimaging and neuropathological data allowed us to distinguish at least five cortical malformation syndromes: (i) microlissencephaly (n = 12); (ii) lissencephaly (n = 19); (iii) central pachygyria and polymicrogyria-like cortical dysplasia (n = 24); (iv) generalized polymicrogyria-like cortical dysplasia (n = 6); and (v) a 'simplified' gyral pattern with area of focal polymicrogyria (n = 19). Dysmorphic basal ganglia are the hallmark of tubulinopathies (found in 75% of cases) and are present in 100% of central pachygyria and polymicrogyria-like cortical dysplasia and simplified gyral malformation syndromes. Tubulinopathies are also characterized by a high prevalence of corpus callosum agenesis (32/80; 40%), and mild to severe cerebellar hypoplasia and dysplasia (63/80; 78.7%). Foetal cases (n = 25) represent the severe end of the spectrum and show specific abnormalities that provide insights into the underlying pathophysiology. The overall complexity of tubulinopathies reflects the pleiotropic effects of tubulins and their specific spatio-temporal profiles of expression. In line with previous reports, this large cohort further clarifies overlapping phenotypes between tubulinopathies and although current structural data do not allow prediction of mutation-related phenotypes, within each mutated gene there is an associated predominant pattern of cortical dysgenesis allowing some phenotype-genotype correlation. The core phenotype of TUBA1A and TUBG1 tubulinopathies are lissencephalies and microlissencephalies, whereas TUBB2B tubulinopathies show in the majority, centrally predominant polymicrogyria-like cortical dysplasia. By contrast, TUBB3 and TUBB5 mutations cause milder malformations with focal or multifocal polymicrogyria-like cortical dysplasia with abnormal and simplified gyral pattern.
The frequentation of places of commerce responds to gendered logics. The methods of consumption of men and women differ by their temporality, the nature of the demand, places frequented and ...purchasing power. Living standards, family structures and greater job insecurity make the female population more exposed to the vagaries of uncontrolled consumption. Based on the results of several field surveys carried out during the health crisis, this article proposes to explain how the analysis of consumption practices during the different phases of lockdown and reopening makes it possible to refine this reading of the gendered use of merchant places. We assume that this crisis, through the economic, family and professional reorganisations it has caused, has reinforced the gendered dimension of the relationship of individuals to places of consumption. The article allows us to see, using the Covid crisis as a revelation, how the gendered differentiation of consumption practices evolves.
BackgroundAnorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is ...influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.The present study will aim to identify markers that can predict body mass index (BMI) stability 6 months after discharge. The secondary aim of this study will be focused on characterising the biological, genetic, epigenetic and neurocognitive markers of remission in AN.Methods and analysisOne hundred and twenty-five (n=125) female adult inpatients diagnosed with AN will be recruited and evaluated at three different times: at the beginning of hospitalisation, when discharged and 6 months later. Depending on the BMI at the third visit, patients will be split into two groups: stable remission (BMI≥18.5 kg/m²) or unstable remission (BMI<18.5 kg/m²). One hundred (n=100) volunteers will be included as healthy controls.Each visit will consist in self-reported inventories (measuring depression, anxiety, suicidal thoughts and feelings, eating disorders symptoms, exercise addiction and the presence of comorbidities), neurocognitive tasks (Delay Discounting Task, Trail-Making Test, Brixton Test and Slip-of-action Task), the collection of blood samples, the repeated collection of blood samples around a standard meal and MRI scans at rest and while resolving a delay discounting task.Analyses will mainly consist in comparing patients stabilised 6 months later and patients who relapsed during these 6 months.Ethics and disseminationInvestigators will ask all participants to give written informed consent prior to participation, and all data will be recorded anonymously. The study will be conducted according to ethics recommendations from the Helsinki declaration (World Medical Association, 2013). It was registered on clinicaltrials.gov on 25 August 2020 as ‘Remission Factors in Anorexia Nervosa (REMANO)’, with the identifier NCT04560517 (for more details, see https://clinicaltrials.gov/ct2/show/record/NCT04560517). The present article is based on the latest protocol version from 29 November 2019. The sponsor, Institut National de la Santé Et de la Recherche Médicale (INSERM, https://www.inserm.fr/), is an academic institution responsible for the monitoring of the study, with an audit planned on a yearly basis.The results will be published after final analysis in the form of scientific articles in peer-reviewed journals and may be presented at national and international conferences.Trial registration number clinicaltrials.govNCT04560517
Ca ²⁺ in neurons is vital to processes such as neurotransmission, neurotoxicity, synaptic development, and gene expression. Disruption of Ca ²⁺ homeostasis occurs in brain aging and in ...neurodegenerative disorders. Membrane transporters, among them the calmodulin (CaM)-activated plasma membrane Ca ²⁺ ATPases (PMCAs) that extrude Ca ²⁺ from the cell, play a key role in neuronal Ca ²⁺ homeostasis. Using X-exome sequencing we have identified a missense mutation (G1107D) in the CaM-binding domain of isoform 3 of the PMCAs in a family with X-linked congenital cerebellar ataxia. PMCA3 is highly expressed in the cerebellum, particularly in the presynaptic terminals of parallel fibers–Purkinje neurons. To study the effects of the mutation on Ca ²⁺ extrusion by the pump, model cells (HeLa) were cotransfected with expression plasmids encoding its mutant or wild-type (wt) variants and with the Ca ²⁺-sensing probe aequorin. The mutation reduced the ability of the PMCA3 pump to control the cellular homeostasis of Ca ²⁺. It significantly slowed the return to baseline of the Ca ²⁺ transient induced by an inositol-trisphosphate (InsP ₃)-linked plasma membrane agonist. It also compromised the ability of the pump to oppose the influx of Ca ²⁺ through the plasma membrane capacitative channels.
LEAP-2 is a ghrelin antagonist with an anorexigenic drive. This study investigates the evolution of plasma ghrelin and LEAP-2 concentrations in 29 patients with anorexia nervosa (AN) before and after ...refeeding and compares it to physiological adaptations during fasting in healthy controls or to mouse model of chronic food restriction and refeeding. Acute and chronic food restriction decrease LEAP-2 and increase ghrelin concentrations in both humans and mice, while patients with AN displayed higher ghrelin and LEAP-2 concentrations before than after refeeding (p = 0.043). After 6 months follow-up, patients with unstable weight gain (n = 17) had significantly decreased LEAP-2 concentrations after refeeding (p = 0.044), in contrast to patients with stable weight gain (n = 12). We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN, in contrast to what is physiologically expected when coping with food restriction.
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•Low LEAP-2 is a biomarker of undernutrition in physiological conditions•Patients with AN display higher LEAP-2 levels in undernourished compared to refed state•Abnormal LEAP-2 regulation during refeeding is associated with unstable remission
Health sciences; Medicine; Psychiatry; Endocrinology; Natural sciences; Biological sciences; Endocrinology; Nutrition
Oligophrenin-1 (OPHN1) is a Rho-GTPase-activating protein (RhoGAP), whose mutations are associated with X-linked intellectual disability (XLID). OPHN1 is enriched at the synapse in both pre- and ...postsynaptic compartments, where it regulates the RhoA/ROCK/MLC2 signaling pathway, playing a critical role in cytoskeleton remodeling and vesicle recycling.
knockout (KO) adult mice display some behavioral deficits in multiple tasks, reminiscent of some symptoms in the human pathology. We also previously reported a reduction in dendritic spine density in the adult hippocampus of KO mice. Yet the nature of the deficits occurring in these mice during postnatal development remains elusive. Here, we show that juvenile KO mice present normal basal synaptic transmission, but altered synaptic plasticity, with a selective impairment in long-term depression, but no change in long-term potentiation. This contrasts with the functional deficits that these mice display at the adult stage, as we found that both basal synaptic transmission and long-term potentiation are reduced at later stages, due to presynaptic alterations. In addition, the number of excitatory synapses in adult is increased, suggesting some unsuccessful compensation. Altogether, these results suggest that OPHN1 function at synapses is differentially affected during maturation of the brain, which provides some therapeutic opportunities for early intervention.
L’appréhension de la centralité marchande s’est longtemps appuyée sur le binôme accessibilité-attractivité. Cela a généré une survalorisation du rôle de la polarisation, et donc des centres, dans la ...structuration de la distribution spatiale des activités marchandes. Pourtant ce binôme accessibilité – attractivité est de moins en moins pertinent alors que nous sommes de plus en plus mobiles. Est-ce un découplage durable du centre et de la centralité ? Est-ce la fin du centre comme lieu privilégié de l’expression marchande ? Assurément non. Ainsi, l’appréhension des rapports spatiaux entretenus entre la fonction marchande et l’espace nous amène à envisager quatre modes de centralité différents : centralité de polarisation, centralité d’ancrage, centralité de positionnement, centralité en distanciel. Pour chacun d’entre eux, le rapport centre-centralité se redessine selon des règles et des motivations différentes. L’article, à portée épistémologique et théorique, propose de faire le point sur cette pluralité de la centralité marchande et de ses rapports entretenus avec la concentration marchande sous forme de centres.
Abstract
Genetic findings reported by our group and others showed that de novo missense variants in the KIF2A gene underlie malformations of brain development called pachygyria and microcephaly. ...Though KIF2A is known as member of the Kinesin-13 family involved in the regulation of microtubule end dynamics through its ATP dependent MT-depolymerase activity, how KIF2A variants lead to brain malformations is still largely unknown. Using cellular and in utero electroporation approaches, we show here that KIF2A disease-causing variants disrupts projection neuron positioning and interneuron migration, as well as progenitors proliferation. Interestingly, further dissection of this latter process revealed that ciliogenesis regulation is also altered during progenitors cell cycle. Altogether, our data suggest that deregulation of the coupling between ciliogenesis and cell cycle might contribute to the pathogenesis of KIF2A-related brain malformations. They also raise the issue whether ciliogenesis defects are a hallmark of other brain malformations, such as those related to tubulins and MT-motor proteins variants.
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