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Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo. This translates into rapid regulation of astroglial structural and functional properties including cytoskeletal plasticity, coverage of synapses and gap-junction coupling. At the molecular level, we identify the previously undescribed Sp1-Gem signaling cascade as the key driver for these cell type-specific OXT effects. Finally at the behavioral level, we found in vivo that OXT requires astrocytes to exert its well described anxiolytic properties within the hypothalamic paraventricular nucleus. Thus, our study points to OXT receptor-expressing astrocytes as a critical component of the brain OXT system.

This paper analyzes the concomitant link between the evolution of purchasing policy and the evolution of supply chain management. The duality of the mode of coordination of the suppliers depends on the relationship between the architect and the first-tier suppliers, according to the strategic degree of their competence. The contribution of this paper is to illuminate the plasticity, the adaptation of the purchasing strategy. The purchasing strategy therefore adapts to the nature of the equipment or systems outsourced, the stakes and expectations are not at all the same. The more complex the product manufactured by the subcontractor, the more the purchasing strategy will seek the mastery of a particular skill. The more standard the product, the more the purchasing strategy aims at reducing costs. The purpose of this paper is twofold. We will show, on the one hand, that there is within the same productive organization a duality of modes of coordination, On the other hand that there is an interaction between the purchasing strategy and these different modes of coordination.

In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes.

The solubilization of fatty acids by small amphiphiles such as butyl ethylene glycol, butyl or pentyl diethylene glycol, and hexyl triethylene glycol, also called hydrotropes, was demonstrated by the determination of their phase diagram. They were thus applied for the passive extraction at room temperature of lipids from Dunaliella salinamicroalgae. The extraction yield of the lipidic fraction (mainly coming from glycolipids), could reach up to 81%, depending of the nature of the hydrotrope and its concentration. In addition, their cloud point properties allow the easy separation of the organic fraction, and their low boiling points allow their recovery with a lower energetic cost than the energetic content of the solubilized lipids. They can also directly be used for the transesterification of the lipids to give the corresponding fatty esters, which may be used as biofuels.

To describe daily practices regarding safety monitoring of methotrexate prescribed at low-(i.e.≤30mg/week). To identify determinants of these practices. To assess association between monitoring and early methotrexate discontinuation.

We sought to assess the quality of dermatological systematic reviews (SRs) and identify factors that predict high methodological quality. We searched for all SRs published in 2017 using PubMed, Epistemonikos, and the Cochrane Database of SRs. We included studies identified as SRs or meta-analysis in the title or abstract and dealing with a dermatological topic. Study selection and data extraction were carried out and Preferred Reporting Items for SRs and Meta-Analyses and rating by A MeaSurement Tool to Assess SRs 2 were used independently by two authors. On the basis of A MeaSurement Tool to Assess SRs 2, confidence in SRs results was classified as high, moderate, low, or very low. We included 732 studies. We described a random sample of 140. The overall rating of confidence in the results according to a tool called A MeaSurement Tool to Assess SRs 2 was high or moderate for nine reviews (6%). A total of 20 reviews (15%) had a registered protocol. Independent factors associated with moderate or high rating of A MeaSurement Tool to Assess SRs 2 were publication in a journal where Preferred Reporting Items for SRs and Meta-Analyses was mandatory (OR [95% confidence interval] = 27.0 [1.4–528]) and journal impact factor (OR of 1.9 [1.3–3]) for each increase in one more point. The observation that 90% of published dermatology SRs are of very low quality is alarming. Review registration in the International Prospective Register of SRs and full reporting according to Preferred Items for SRs and Meta-Analyses should be mandatory for publication.

The synthesis of a tridentate NNN ligand incorporating an amidoquinoline and an iminophosphorane (LRH; R = Ph, Cy) was carried out. Coordination to PdIIand NiIIprecursors gave, as expected, square-planar complexes of the general formula [LRMCl]. The most surprising result came from the reaction of LPhHwith [Ni(COD)2], which gave a NiIIphenyl complex bearing a tridentate amidoquinoline-aminophosphine ligand. This rearrangement would result from a proton transfer assisted by the Ni0on stabilization by a phenyl substituent at the phosphorus, as suggested by DFT calculations and complementary experiments. This nickel phenyl complex formed the corresponding benzoyl complex under a CO atmosphere.

Les nævus éruptifs sont un phénomène rare caractérisé par l’apparition rapide et simultanée de multiples nævus. Il a été décrit dans différents contextes : immunodépression, médicaments immunosuppresseurs, thérapies ciblées, maladies bulleuses ou stimulation mélanocytaire chimique. Nous rapportons 3 observations de nævus éruptifs survenus après traitement par anti-TNF alpha.

Le règlement européen qui régit la mise sur le marché des dispositifs médicaux (DM) prévoit la mise en place progressive et obligatoire, au sein de l’Union européenne, d’un système d’identification unique (IUD) et d’une base de données européenne (EUDAMED) dans un objectif d’amélioration de la traçabilité et de la transparence du marché. Le déploiement de ces outils va fortement impacter les acteurs du dispositif médical (entreprises, établissements de santé, professionnels de santé, autorités compétentes…). Une analyse de type menaces/opportunités/forces/faiblesses (MOFF) conduite auprès des participants à la table ronde montre une réelle adhésion aux objectifs mais également l’existence de nombreuses interrogations relatives à la mise en place opérationnelle de ces outils. Un état des lieux de l’existant en matière d’outils de traçabilité et de bases de données utilisées en France a ensuite été réalisé pour mesurer les écarts entre les exigences du règlement européen et l’existant. Au final, EUDAMED et le système IUD vont devoir s’intégrer dans un écosystème complexe et peu interopérable. Une première étape essentielle pour faciliter cette intégration sera de multiplier les actions de pédagogie, de sensibilisation et d’information auprès des acteurs concernés. Plusieurs autres recommandations ont été formulées pour accompagner l’implémentation d’EUDAMED et du système IUD en France et permettre, ainsi, que leurs promesses puissent un jour devenir réalité.

The European regulation governing the placing on the market of medical devices (MD) provides for the gradual and mandatory phasing-in, within the European Union, of a unique device identification (UDI) system and a European database (EUDAMED) aimed at improving traceability and transparency of the market. The deployment of these tools will have a significant impact on the stakeholders of the medical device world (companies, health institutions, healthcare professionals, competent authorities, etc.). A strengths/weaknesses/opportunities/threats (SWOT) analysis conducted among the think tank participants shows real support for the objectives but also distinguishes a great deal of issues relating to the implementation of these tools. An inventory of the current traceability tools and databases used in France was then carried out to measure the gaps between the requirements of the European regulation and the current situation revealing that EUDAMED and the UDI system will ultimately have to slot into a complex and poorly interoperable ecosystem. An essential first step to facilitate this integration will be to increase the number of educational, awareness-raising and information initiatives for the stakeholders concerned. Several other recommendations were put forward to support the implementation of EUDAMED and the UDI system in France and thus enable their promises to crystallise in the future.

The Southern Ocean (SO) plays a fundamental role in global climate due to the presence of the intense eastward‐flowing Antarctic Circumpolar Current (ACC), one of the most important ocean current systems. The configuration of the frontal systems of the ACC is controlled by the orbital‐ and millennial‐scale variations of the Southern Hemisphere westerly winds (SHWW) and the SO upwelling. However, the reconstruction of paleoclimate and paleocurrent in the SO remains controversial possibly because of the complex interpretation of paleo‐proxies and the regional variations. Here, we present results from rock magnetic measurements and electron microscopic analyses on marine core MD11‐3353 over the past 150 Kyr, which is located in the Polar Front Zone, west of the Kerguelen Plateau. Our data sets indicate that magnetic mineral assemblages in the core are dominated by detrital magnetic minerals mixed with biogenic magnetic minerals (i.e., magnetofossils formed by magnetotactic bacteria) during the interglacial periods. Changes in the detrital magnetic mineral content indicate a strong modulation of the ACC intensity and the SHWW stress at the orbital scale over the last climatic cycle with an enhanced activity during the glacial periods. The increase in magnetofossils content during the interglacial periods indicates an enhanced nutrient supply from the SO upwelling resulting from the southward migration of the Antarctic Polar Front. Our results suggest that the variations of concentration and assemblage of magnetic minerals can be used as faithful proxies for reconstructing ocean circulation and upwelling changes in the South Indian Ocean over the past 150 Kyr. The Southern Ocean plays a critical role in climate, ocean circulation, oceanic carbon sequestration, and nutrient distribution, in particular via the Antarctic Circumpolar Current (ACC), the largest wind‐driven current on Earth. Reconstructing the past variability of the intensity and position of the ACC is challenging. Indeed, rather different results were obtained from different areas suggesting a strong regional dependence. In order to better decipher the mechanisms involved in the southern Indian sector, we performed detailed environmental magnetic analyses on a marine core collected west of the Kerguelen Plateau, presently under the influence of the ACC. Both detrital and biogenic magnetic minerals were identified over the past 150 Kyr, corresponding to the last climatic cycle. The temporal variations of detrital magnetic minerals suggest an enhanced intensity of the ACC during the glacial periods. In contrast, increased abundance of biogenic magnetic minerals during the interglacial periods indicates an increased nutrient supply associated with an enhanced Southern Ocean upwelling. Magnetic minerals in core MD11‐3353 record paleoenvironmental changes in the South Indian Ocean over the past 150 KyrAbundant detrital magnetic minerals illustrate an enhanced intensity of the Antarctic Circumpolar Current during the glacial periodsIncreased magnetofossils indicate an increased nutrient supply associated with the Southern Ocean upwelling during the interglacial periods Magnetic minerals in core MD11‐3353 record paleoenvironmental changes in the South Indian Ocean over the past 150 Kyr Abundant detrital magnetic minerals illustrate an enhanced intensity of the Antarctic Circumpolar Current during the glacial periods Increased magnetofossils indicate an increased nutrient supply associated with the Southern Ocean upwelling during the interglacial periods

A rise in the atmospheric CO2concentration of ~20 parts per million over the course of the Holocene has long been recognized as exceptional among interglacials and is in need of explanation. Previous hypotheses involved natural or anthropogenic changes in terrestrial biomass, carbonate compensation in response to deglacial outgassing of oceanic CO2, and enhanced shallow water carbonate deposition. Here, we compile new and previously published fossil-bound nitrogen isotope records from the Southern Ocean that indicate a rise in surface nitrate concentration through the Holocene. When coupled with increasing or constant export production, these data suggest an acceleration of nitrate supply to the Southern Ocean surface from underlying deep water. This change would have weakened the ocean’s biological pump that stores CO2in the ocean interior, possibly explaining the Holocene atmospheric CO2rise. Over the Holocene, the circum-North Atlantic region cooled, and the formation of North Atlantic Deep Water appears to have slowed. Thus, the ‘seesaw’ in deep ocean ventilation between the North Atlantic and the Southern Ocean that has been invoked for millennial-scale events, deglaciations and the last interglacial period may have also operated, albeit in a more gradual form, over the Holocene.

ABSTRACTRadiocarbon (14C) measurements of foraminifera often provide the only absolute age constraints in marine sediments. However, they are often challenging as their reliability and accuracy can be compromised by reduced availability of adequate sample material. New analytical advances using the MIni CArbon DAting System (MICADAS) allow 14C dating of very small samples, circumventing size limitations inherent to conventional 14C measurements with accelerator mass spectrometry (AMS). Here we use foraminiferal samples and carbonate standard material to assess the reproducibility and precision of MICADAS 14C analyses, quantify contamination biases, and determine foraminiferal 14C blank levels. The reproducibility of conventional 14C ages for our planktic (benthic) foraminiferal samples from gas measurements is 200 (130) yr, and has good precision as illustrated by the agreement between both standards and their reference values as well as between small gas- and larger graphitized foraminiferal samples (within 100±60 yr). We observe a constant contamination bias and slightly higher 14C blanks for foraminifera than for carbonate reference materials, limiting gas (graphite) 14C age determinations for foraminifera from our study sites to ~38 (~42) kyr. Our findings underline the significance of MICADAS gas analyses for 14C on smaller-than-conventional sized foraminiferal samples for paleoclimate reconstructions and dating.

L’expérimentation du cannabis thérapeutique (CT) a débuté en mars 2021 dans notre centre agrée pour 3 indications : douleurs neuropathiques réfractaires aux thérapies (médicamenteuses ou non) accessibles, certaines épilepsies pharmacorésistantes et spasticité douloureuse de la sclérose en plaques ou autres. La dispensation du CT est réalisée en rétrocession (entretien patient spécifique) avec proposition systématique de création/consultation du dossier pharmaceutique (DP)

Concern has been raised over chemical-induced disruption of ovary development during fetal life resulting in long-lasting consequences only manifesting themselves much later during adulthood. A growing body of evidence suggests that prenatal exposure to the mild analgesic acetaminophen/paracetamol can cause such a scenario. Therefore, in this review, we discuss three recent reports that collectively indicate that prenatal exposure in a period of 13.5 days post coitumin both rats and mouse can result in reduced female reproductive health. The combined data show that the exposure results in the reduction of primordial follicles, irregular menstrual cycle, premature absence of corpus luteum, as well as reduced fertility, resembling premature ovarian insufficiency syndrome in humans that is linked to premature menopause. This could especially affect the Western parts of the world, where the age for childbirth is continuously being increased and acetaminophen is recommended during pregnancy for pain and fever. We therefore highlight an urgent need for more studies to verify these data including both experimental and epidemiological approaches.

Les tensions d’approvisionnements sont devenues le quotidien d’un pharmacien hospitalier avec une activité chronophage. Une procédure a été mise en place afin que l’information soit captée, vérifiée, analysée et transmise à tous les professionnels de santé.

Depuis les dernières années, une tendance s’observe, lorsqu’il est nécessaire de distaler les molaires supérieures, à utiliser de façon préférentielle des appareils uniquement intra-oraux sollicitant le moins possible la coopération du patient. Malheureusement, la plupart des appareils de distalisation molaire habituellement utilisés en cas d’absence de coopération, engendrent des effets secondaires indésirables tels que la perte d’ancrage. De façon à minimiser ou éviter cette perte d’ancrage, les mini-vis sont d’un grand intérêt depuis quelques années; ceci par leur caractère faiblement invasif chirurgicalement et par leur faible coût. En utilisant la région antérieure du palais comme site d’insertion, le taux d’échec est extrêmement bas; il n’y a pas de risque d’atteinte radiculaire et les appareils sont à distance des mouvements orthodontiques provoqués. Fondées sur une documentation clinique explicite, les applications pratiques et rationnelles du Beneslider associé à des attaches linguales sont présentées. Par cette procédure, les extractions à l’arcade supérieure et les forces réactives à l’arcade mandibulaire entraînant une vestibulo-version des incisives peuvent être évitées avec une thérapeutique utilisant un appareil invisible.

La sécurisation du circuit du médicament (CDM) ou de la « prise en charge médicamenteuse » constituait une priorité des établissements de santé depuis la réforme hospitalière du plan « hôpital 2007 ». Les objectifs de cette étude étaient de décrire et d’évaluer l’impact du projet SAM (Simplifier, Améliorer et Moderniser les processus logistiques) sur la gestion des stocks, le coût, le gain en personnel dans un service de réanimation pédiatrique (RP). À partir de 2007, le service de RP du CHU de Lille se portait candidat au projet SAM. En 2008, sur la base des consommations de l’année 2007 de tous les médicaments, solutés, DM et matériels non médicaux, une dotation était élaborée. Après un appel à projets, le système de dotation de gestion en plein-vide (SPV) dans des armoires à pharmacie et de rangement était choisi. Une estimation du temps gagné était effectuée. Le stock « mort » diminuait de 69 % (94 816 €) en valeur, et de 18 % en nombre de références stockées dans le service. Le gain hebdomadaire de temps soignant (88,5 heures) en 2008 était réinvesti dans 0,8 poste équivalent temps plein d’auxiliaire de puériculture. Les temps additionnels hebdomadaires de la pharmacie et du service logistique étaient respectivement de 9,5 et 5 heures sans création de poste. Lors des deux enquêtes, de manière globale, le projet a été bien accepté et adopté par les équipes de soignants et de la pharmacie. Le sentiment général était l’amélioration de la qualité des soins et de la surveillance des patients. L’expérience du projet SAM par système de gestion d’une liste de dotation en plein-vide (médicaments, DM, solutés et matériel) a montré son intérêt en partie grâce à lamise en oeuvre d’une réorganisation spatiale du service et un transfert de tâches vers la pharmacie et les services logistiques. Ce projet a permis une réinjection de temps dans les soins directs aux patients, un sentiment d’amélioration de la qualité des soins et de la surveillance des patients, et le décloisonnement entre la pharmacie et l’unité de soins. Ce système apporte un début de réponse à la réglementation et constitue un excellent tremplin en vue de l’informatisation du CDM. The objective of this study was to describe and to evaluate a Simplification, Improvement and Modernization project (SAM) of logistics processes in a pediatric intensive care unit. SAM includes a full-empty system for the supply chain management (drugs, medical devices, solutes and hygiene equipment). It required spatial reorganization of the unit and the implementation of a pharmacy performance. In late 2008, after an analysis, endowment was managed by full-empty system with Radio Frequency Identification using Scan Modul System Data software. The immobilized stock decreased of 69 % (94,816 Euros in amount), and 18 % in number of references stored in the unit. The weekly time gain of the nurses (88.5 hours) in 2008 was reinvested in 0.8 full-time equivalent of childcare assistant. Additional weekly time for the pharmacy and the logistic units was respectively 9.5 and 5 hours without job creation. In both surveys, the system was well accepted by actors. The general feeling was the improvement of quality of care and patient monitoring. This study has shown the interest in a computerized full-empty system for the supply chain management. This project required a working time reallocation in particular for the logistical tasks (additional tasks transferred to the pharmacy). It improved quality of care and patient monitoring and strengthened communication between actors.

Mild analgesics (hereafter, analgesics) consisting of paracetamol and NSAIDs are among the most used pharmaceutical drugs worldwide as well as the most released into the environmentEpidemiological data indicate a connection between maternal intake of analgesics and congenital reproductive abnormalitiesAnalgesics can have endocrine-disruptive actions in animals and humans of both sexes, from fetal life to adulthoodMedical and public awareness (especially that of pregnant women) must be increased about the potential hazards of analgesic use

Dans le domaine de l’ancrage squelettique, le recours aux mini-implants orthodontiques ne cesse de se développer. Cependant, le principal problème reste leur taux relativement élevé de perte de 16,4 %. Si l’on analyse les publications traitant des causes de perte d’implants, il s’avère que l’insertion de mini-implants plus importants en taille dans la région antérieure et médiane du palais aboutit à une grande stabilité ainsi qu’à un taux élevé de succès. De plus, la stabilité du couplage mini-implant/suprastructure est déterminante dans le succès. L’utilisation de mini-implants dont la tête possède un pas de vis interne permet la mise en place vissée stable de différents types d’abutments (piliers). Grâce à de longues plaques perforées spéciales, il est possible de relier deux mini-implants entre eux et d’augmenter ainsi leur stabilité. Un système d’éléments préfabriqués permet l’élaboration rapide de différents types de mécaniques orthodontiques efficaces (systèmes mécaniques efficaces).

Tissue integrity relies on barriers formed between epithelial cells. In the testis, the barrier is formed at the initiation of puberty by a tight junction complex between adjacent Sertoli cells, thereby defining an adluminal compartment where meiosis and spermiogenesis occur. Claudin 11 is an obligatory protein for tight junction formation and barrier integrity in the testis. It is expressed by Sertoli cells, and spermatogenesis does not proceed beyond meiosis in its absence, resulting in male sterility. Sertoli cell maturation—arrest of proliferation and expression of proteins to support germ cell development—parallels tight junction assembly; however, the pathophysiology underlying the loss of tight junctions in the mature testis remains largely undefined. Here, using immunohistochemistry and microarrays we demonstrate that adult Cldn11−/−mouse Sertoli cells can proliferate while maintaining expression of mature markers. Sertoli cells detach from the basement membrane, acquire a fibroblast cell shape, are eliminated through the lumen together with apoptotic germ cells, and are found in epididymis. These changes are associated with tight junction regulation as well as actin-related and cell cycle gene expression. Thus, Cldn11−/−Sertoli cells exhibit a unique phenotype whereby loss of tight junction integrity results in loss of the epithelial phenotype.

The GATA4 transcription factor is an important developmental determinant for many organs, such as the heart, gut, and testis. Despite this pivotal role, our understanding of the transcriptional mechanisms that control the proper spatiotemporal expression of the GATA4gene remains limited. We have generated transgenic mice expressing a green fluorescent protein (GFP) marker under the control of rat Gata45′ flanking sequences. Several GATA4-expressing organs displayed GFP fluorescence, including the heart, intestine, and pancreas. In the gonads, while GATA4 is expressed in pregranulosa, granulosa, and theca ovarian cells, and Sertoli, Leydig, and peritubular testicular cells, the first 5 kb of Gata4regulatory sequences immediately upstream of exon 1 were sufficient to direct GFP reporter expression only in testis and, specifically, in Sertoli cells. Onset of GFP expression occurred after Sertoli cell commitment and was maintained in these cells throughout development to adulthood. In vitro studies revealed that the first 118 bp of the Gata4promoter is sufficient for full basal activity in several GATA4-expressing cell lines. Promoter mutagenesis and DNA-binding experiments identified two GC-box motifs and, particularly, one E-box element within this −118-bp region that are crucial for its activity. Further analysis revealed that members of the USF family of transcription factors, especially USF2, bind to and activate the Gata4promoter via this critical E-box motif.

En mars 2018, le recueil des indications des molécules onéreuses (m.o.) inscrites sur la liste en sus est devenu obligatoire pour le PMSI MCO. Depuis septembre 2018, les indications doivent être renseignées pour bénéficier du remboursement. Le code indication I999999 signifiant “hors AMM justifié” est accepté jusqu’en février 2019 comme code par défaut pour toute indication, masquant ainsi la vraie part d’“hors AMM justifié”. Parmi les indications des m.o. certaines ne sont plus remboursées, mettant ainsi en application la LFSS 2014, application jusque-là réservée à des cas particuliers (ex. Avastin 1). En 2018, le montant des m.o. en MCO s’élève à 3,4 milliards. Notre objectif est de décrire l’impact de ces obligations réglementaires sur les informations transmises via le PMSI, et plus globalement de comprendre le risque financier pour les établissements.

Le recueil des indications des spécialités pharmaceutiques inscrites sur la liste en sus a été rendu obligatoire à partir de mars 2018. A partir de septembre 2018 les indications devaient être renseignées pour être remboursées. Notre objectif est de décrire l’impact de ces obligations règlementaires sur les informations transmises via le programme de médicalisation des systèmes d’information (PMSI).

Follicle histogenesis, in which follicles arise from fragmenting ovigerous cords, is a poorly understood mechanism that is strictly dependent upon the presence of germ cells. Our previous studies have shown that severely germ cell-depleted rat ovaries after fetal gamma-irradiation display modifications of follicular endowment and dynamics during the immature period. The primordial follicle stock was absent and the follicles with primary appearance remained quiescent longer than in control ovaries during the neonatal period. The aim of the present work was to analyze the initial steps of follicle histogenesis, and to investigate the etiology of the alterations observed in the development of irradiated ovaries. Just after birth, we observed, in addition to sterile ovigerous cords, the emergence of the first follicles which exhibited several abnormal features as compared to those of control ovaries. Most of the follicles appeared as primary follicles, as they were composed of a layer of cuboidal-shaped granulosa cells surrounding an enlarged oocyte. Interestingly, the granulosa cells of these primary-like follicles did not proliferate and did not express the genes for anti-Müllerian hormone (Amh)or bone morphogenetic protein receptor type II (Bmpr2), both of which are normally expressed from the primary stage onwards. In contrast, the oocytes strongly expressed the gene for growth and differentiation factor 9 (Gdf9), which is normally upregulated from the primary follicle stage onwards, which suggests an uncoupling of granulosa cell development from oocyte development. In addition, irradiated ovaries displayed a higher frequency of follicles that contained 2 or 3 oocytes, which are also referred to as multi-oocyte follicles (MOFs). Examination at the time of follicle histogenesis indicated that MOFs arise from incomplete ovigerous cord breakdown. Taken together, the results of this study indicate that severe perturbations of follicular histogenesis take place following irradiation and massive germ cell depletion during fetal life. In addition to the classically described sterile cords, we have pointed out the differentiation of MOFs and primary-like quiescent follicles, which finally evolve into growing follicles and participate in ovarian function. We propose that these phenotypes are closely correlated to the proportion of granulosa cells to oocytes at the time of neonatal follicle histogenesis.

This article addresses the issue of the uses of the multidivisional form in the French context at the end of the 1960s and the beginning of the 1970s. Comparing two case studies, Danone and Hachette, it sheds light on specific experiences in two different industries, the food and the book industry, respectively, in order to contribute to the debate over the Chandlerian paradigm. These two cases show that the implementation of the M-form in European companies can neither be reduced to the necessary diffusion of a universal structure nor to managerial fashion. At first a matter of redistributing the power between the shareholders and the management, the M-form led to hybrid organizations with characteristics heavily dependent on intensive internal negotiations. These findings emphasize the potential diversity of the implementation of the M-form and of the relations between management and shareholders. Far from being linear, company trajectories then heavily depend on partial compromises.

This article addresses the issue of the uses of the multidivisional form in the French context at the end of the 1960s and the beginning of the 1970s. Comparing two case studies, Danone and Hachette, it sheds light on specific experiences in two different industries, the food and the book industry, respectively, in order to contribute to the debate over the Chandlerian paradigm. These two cases show that the implementation of the M-form in European companies can neither be reduced to the necessary diffusion of a universal structure nor to managerial fashion. At first a matter of redistributing the power between the shareholders and the management, the M-form led to hybrid organizations with characteristics heavily dependent on intensive internal negotiations. These findings emphasize the potential diversity of the implementation of the M-form and of the relations between management and shareholders. Far from being linear, company trajectories then heavily depend on partial compromises.

The role of fibroblast growth factor (FGF) 2 and FGF9 as mediators of cell–cell interactions between Sertoli cells (SCs) and peritubular cells (PCs) was investigated. Using RT-PCR, we demonstrated that SCs and PCs recovered from 20-day-old rats expressed several of the seven FGF receptors (FGFRs), and more specifically the FGFR1 IIIc. FGF2 and FGF9 did not elicit any morphological changes in primary cultures of SCs, nor did they alter the number of SCs in culture. By contrast, changes in shape were observed in FGF2- and FGF9-treated PCs. In addition, FGF2 but not FGF9 enhanced significantly and dose-dependently the number of PCs in culture, indicating that FGF2 was a survival factor for these cells. It was also mitogenic because it enhanced the [3H]thymidine labeling index in PCs. We next examined the effects of FGF2 and FGF9 in a coculture system using 20-day-old rat SCs and PCs, and in an organotypic culture system using XY rat embryonic gonads. In both models, FGF2 and FGF9 were found to promote cellular interactions as evidenced by the extent of cellular reorganization in the coculture system, and cord morphogenesis and growth in the organotypic culture system. A key feature in SC–PC interactions is the synthesis and remodeling of the basement membrane which is co-elaborated by the two cell types. Since basement membrane homeostasis depends upon the coordinated activity of proteinases and inhibitors, the proteinases and inhibitors produced by PCs and SCs degrading or opposing degradation of the major components of the basement membrane were further studied. Specifically, we monitored the metalloproteinases (MMP)- 2 and -9 and the tissue inhibitors -1, -2 and -3, the plasminogen activators (PAs) and the PA inhibitor-1, using zymography for the proteinases and Western blots for the cognate inhibitors. Cocultures received FGF or an analog of cAMP in order to prevent cellular reorganization. We found that FGF2 was unique in inducing MMP-9 in coculture. Also, the enhanced levels of the PA inhibitor-1 and the 30 kDa band glycosylated form of tissue inhibitor-3 correlated with the enhanced SC–PC reorganization. It was concluded that FGF2 and FGF9 are morphogens for the formation of testicular cords.

In mammals, anti-Müllerian hormone (AMH) is produced by Sertoli cells from the onset of testicular differentiation and by granulosa cells after birth. In birds, AMH starts to be expressed in indifferent gonads of both sexes at a similar level and is later up-regulated in males. We previously demonstrated that, unlike in mammals, the onset of AMH expression occurs in chick embryo in the absence of SOX9. We looked for potential factors that might be involved in regulating AMH expression at different stages of chick gonad differentiation by comparing its expression pattern in embryos and young chicken with that of DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9, by in situ hybridization. The results allowed us to distinguish different phases. (1) In indifferent gonads of both sexes, AMH is expressed in dispersed medullar cells. SF-1, WT1, GATA-4, Wnt-4, and DMRT1 are transcribed in the same region of the gonads, but none of these factors has an expression strictly coincident with that of AMH. Lhx9 is present only in the cortical area. (2) After this period, AMH is up-regulated in male gonads. The up-regulation is concomitant with the beginning of SOX9 expression and a sex dimorphic level of DMRT1 transcripts. It is followed by the aggregation of the AMH-positive cells (Sertoli cells) into testicular cords in which AMH is coexpressed with DMRT1, SF-1, WT1, GATA-4, and SOX9. (3) In the females, the low level of dispersed medullar AMH expression is conserved. With development of the cortex in the left ovary, cells expressing AMH accumulate in the juxtacortical part of the medulla, whereas they remain dispersed in the right ovary. At this stage, AMH expression is not strictly correlated with any of the studied factors. (4) After hatching, the organization of left ovarian cortex is characterized by the formation of follicles. Follicular cells express AMH in conjunction with SF-1, WT1, and GATA-4 and in the absence of SOX9, as in mammals. In addition, they express Lhx9 and Wnt-4, the latter being also found in the oocytes. (5) Moreover, unlike in mammals, the chicken ovary retains a dispersed AMH expression in cortical interstitial cells between the follicles, with no obvious correlation with any of the factors studied. Thus, the dispersed type of AMH expression in indifferent and female gonads appears to be bird-specific and not controlled by the same factors as testicular or follicular AMH transcription. © 2002 Wiley-Liss, Inc.

Several factors have led to intensified public scrutiny of the human food supply chain. Consumer concerns for food safety, animal welfare, and the environmental and ecological impact of food production and agro-processing have become increasingly important. These concerns have been exacerbated by several factors, including the trend towards further globalization of the food supply chain, the incidence of new and emerging safety hazards such as the human form of BSE (mad cow disease), and illnesses and deaths resulting from contamination of fresh and processed food. As a consequence of these growing concerns, consumers and other stakeholders in agroindustry now demand transparency in the way food is grown and handled throughout the supply chain, resulting in the emergence of 'traceability' as an important policy issue in food quality and safety. This paper provides a global overview of 'traceability' as a quality index in food trade, and discusses some of the drivers in both developed and developing countries. Policy changes are necessary specifically to incorporate traceability into existing food safety regulations and trade agreements. This will require further investments in information technology for data capture, storage and retrieval. Small-scale farmers in many developing regions moving towards market orientation face considerable technical and financial challenges in implementing appropriate food traceability systems in order to meet marketing compliance requirements.

Several factors have led to intensified public scrutiny of the human food supply chain. Consumer concerns for food safety, animal welfare, and the environmental and ecological impact of food production and agro-processing have become increasingly important. These concerns have been exacerbated by several factors, including the trend towards further globalization of the food supply chain, the incidence of new and emerging safety hazards such as the human form of BSE (mad cow disease), and illnesses and deaths resulting from contamination of fresh and processed food. As a consequence of these growing concerns, consumers and other stakeholders in agroindustry now demand transparency in the way food is grown and handled throughout the supply chain, resulting in the emergence of ‘traceability’ as an important policy issue in food quality and safety. This paper provides a global overview of ‘traceability’ as a quality index in food trade, and discusses some of the drivers in both developed and developing countries. Policy changes are necessary specifically to incorporate traceability into existing food safety regulations and trade agreements. This will require further investments in information technology for data capture, storage and retrieval. Small-scale farmers in many developing regions moving towards market orientation face considerable technical and financial challenges in implementing appropriate food traceability systems in order to meet marketing compliance requirements.

Six relative palaeointensity records from the north Atlantic Ocean were stacked together to produce a new record for the last 75 kyr (NAPIS–75). Five of these records have been previously correlated at millennial scale and placed on the GISP2 age scale, the sixth record was tied to the others using magnetic susceptibility. From 75 ka the field strength exhibits some oscillations, with a first minimum ca.65 ka, followed by a progressive increase to a broad maximum centred at ca.48 ka. There is then a well–marked low at 40 ka, corresponding to the directional anomaly of the Laschamp event. Another intensity low, observed at ca.34 ka, corresponds in age to the Mono Lake event. After a high at 33 ka and two lows at 30 and 24 ka with a broad maximum between, the field strength seems to slowly increase to the upper limit of the studied interval. In the 10–20 kyr interval some differences exist between individual records, and fine–scale details are not always resolved. In the 20–75 kyr interval, on the other hand, well–resolved millennial–scale features are superimposed to the broader trends. The duration of the Laschamp event, which is recorded directionally in five cores, appears to be about 1500 years, consistent with a recent suggestion on the origin of geomagnetic excursions.

Little is still known about the origin of somatic progenitor cells of human fetal gonads, their molecular identity and the transcriptional programs controlling their differentiation towards multiple fates. In this study, we performed single-cell RNA-sequencing to characterize cell lineage progression during gonad differentiation and to build the first atlas of human fetal gonads at single cell resolution.

Recent records of normalised intensity of natural remanent magnetization (NRM) obtained from deep-sea sediments document an asymmetrical saw-tooth pattern, associated with geomagnetic reversals. This observation may reflect a fundamental aspect of the geodynamo time evolution or, alternatively, delay in acquisition of the NRM. It is demonstrated here that a simple model, in which a large fraction of the magnetic grains acquire NRM at deposition time while remaining grains reorientate or acquire magnetization after deposition, is able to produce a ‘saw-tooth’ profile strikingly similar to that observed. Interestingly, this mechanism of NRM acquisition does not damp out high frequency oscillations of the field, such as those observed in the deep-sea records exhibiting the saw-tooth profile. It provides an accurate record of field directions, except for periods of very low field intensity.

SDS‐PAGE and N‐tenninal sequence analysis of hydrolysis products from 3 substrates containing a unique sensitive bond usually recognized by chymosin (k‐casein, a synthetic hexapeptide and a recombinant tripartite protein) revealed that a 45 kDa endoprotease of Myxococcus xanthusDK101 cleaved the same characteristic Phe‐Met bond with high specificity. Such an enzyme, easy to obtain from culture supernatant and to use in acidic conditions, could be a new tool for protein engineering.

SDS-PAGE and N-tenninal sequence analysis of hydrolysis products from 3 substrates containing a unique sensitive bond usually recognized by chymosin ( k-casein, a synthetic hexapeptide and a recombinant tripartite protein) revealed that a 45 kDa endoprotease of Myxococcus xanthusDK101 cleaved the same characteristic Phe-Met bond with high specificity. Such an enzyme, easy to obtain from culture supernatant and to use in acidic conditions, could be a new tool for protein engineering.

We have used a new sedimentary record of geomagnetic field intensity, combined with published volcanic data, to examine the extent to which geomagnetic changes have affected 14C production in the past. The production record was then converted into an atmospheric Δ14C signal using a 4‐box model of past oceanic circulation. The results indicate that changes in geomagnetic field intensity account for at least 80% of the Δ14C shift documented by published U‐Th data, which are of the order of 500 per mil with respect to a constant production hypothesis. Model simulations show that changes in past oceanic circulation account for only ±100 per mil of Δ14C variation, which is within the uncertainty of the geomagnetic correction. In terms of dating, these results show that the radiocarbon ages have to be shifted by 2 to 3.5 kyr towards older ages during the 20–40 ka interval.