Cardiac Muscarinic Receptor Overexpression in Sudden Infant Death Syndrome

BACKGROUND: Sudden infant death syndrome (SIDS) remains the leading cause of death among infants less than 1 year of age. Disturbed expression of some neurotransmitters and their receptors has been shown in the central nervous system of SIDS victims but no biological abnormality of the peripheral vago-cardiac system has been demonstrated to date. The present study aimed to seek vago-cardiac abnormalities in SIDS victims. The cardiac level of expression of muscarinic receptors, as well as acetylcholinesterase enzyme activity were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Left ventricular samples and blood samples were obtained from autopsies of SIDS and children deceased from non cardiac causes. Binding experiments performed with [(3)H]NMS, a selective muscarinic ligand, in cardiac membrane preparations showed that the density of cardiac muscarinic receptors was increased as shown by a more than doubled B(max) value in SIDS (n = 9 SIDS versus 8 controls). On average, the erythrocyte acetylcholinesterase enzyme activity was also significantly increased (n = 9 SIDS versus 11 controls). CONCLUSIONS: In the present study, it has been shown for the first time that cardiac muscarinic receptor overexpression is associated with SIDS. The increase of acetylcholinesterase enzyme activity appears as a possible regulatory mechanism

Immunodeficiency, auto-inflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic auto-inflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1, a component the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin-1β (IL-1β) was compromised in the patients’ fibroblasts. By contrast, the patients’ mononuclear leukocytes, particularly monocytes, were hyperresponsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of auto-inflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types

Pour une démocratie socio-environnementale : cadre pour une plate-forme participative « transition écologique »

Contribution publiée in Penser une démocratie alimentaire Volume II – Proposition Lascaux entre ressources naturelles et besoins fondamentaux, F. Collart Dutilleul et T. Bréger (dir), Inida, San José, 2014, pp. 87-111.International audienceL’anthropocène triomphant actuel, avec ses forçages environnementaux et sociaux, est à l’origine de l’accélération des dégradations des milieux de vie sur Terre et de l’accentuation des tensions sociales et géopolitiques. Passer à un anthropocène de gestion équitable, informé et sobre vis-à-vis de toutes les ressources et dans tous les secteurs d’activité (slow anthropocene), impose une analyse préalable sur l’ensemble des activités et des rapports humains. Cette transition dite « écologique », mais en réalité à la fois sociétale et écologique, est tout sauf un ajustement technique de secteurs dits prioritaires et technocratiques. Elle est avant tout culturelle, politique et philosophique au sens propre du terme. Elle est un horizon pour des trajectoires de développement humain, pour des constructions sociales et économiques, censées redéfinir socialement richesse, bien-être, travail etc. La dénomination « transition écologique » est largement véhiculée, mais ses bases conceptuelles ne sont pas entièrement acquises ni même élaborées. Dans ce contexte, les étudiants en première année de Master BioSciences à l’Ecole Normale Supérieure (ENS) de Lyon ont préparé une première étude analytique de ce changement radical et global de société pour mieux comprendre dans quelle société ils souhaitent vivre, en donnant du sens aux activités humaines présentes et à venir. Une trentaine de dossiers sur divers secteurs d’activités et acteurs de la société ont été produits et ont servis de support à cette synthèse. Plus largement, le but est de construire un socle conceptuel et une plate-forme de travail sur lesquels les questions de fond, mais aussi opérationnelles, peuvent être posées et étudiées en permanence. Cette démarche participative est ouverte à la collectivité sur le site http://institutmichelserres.ens-lyon.fr/

Construction and characterization of two BAC libraries representing a deep-coverage of the genome of chicory (Cichorium intybus L., Asteraceae)

<p>Abstract</p> <p>Background</p> <p>The Asteraceae represents an important plant family with respect to the numbers of species present in the wild and used by man. Nonetheless, genomic resources for Asteraceae species are relatively underdeveloped, hampering within species genetic studies as well as comparative genomics studies at the family level. So far, six BAC libraries have been described for the main crops of the family, <it>i.e</it>. lettuce and sunflower. Here we present the characterization of BAC libraries of chicory (<it>Cichorium intybus </it>L.) constructed from two genotypes differing in traits related to sexual and vegetative reproduction. Resolving the molecular mechanisms underlying traits controlling the reproductive system of chicory is a key determinant for hybrid development, and more generally will provide new insights into these traits, which are poorly investigated so far at the molecular level in Asteraceae.</p> <p>Findings</p> <p>Two bacterial artificial chromosome (BAC) libraries, CinS2S2 and CinS1S4, were constructed from <it>Hin</it>dIII-digested high molecular weight DNA of the contrasting genotypes C15 and C30.01, respectively. C15 was hermaphrodite, non-embryogenic, and <it>S</it>₂<it>S</it>₂for the <it>S</it>-locus implicated in self-incompatibility, whereas C30.01 was male sterile, embryogenic, and <it>S</it>₁<it>S</it>₄. The CinS2S2 and CinS1S4 libraries contain 89,088 and 81,408 clones. Mean insert sizes of the CinS2S2 and CinS1S4 clones are 90 and 120 kb, respectively, and provide together a coverage of 12.3 haploid genome equivalents. Contamination with mitochondrial and chloroplast DNA sequences was evaluated with four mitochondrial and four chloroplast specific probes, and was estimated to be 0.024% and 1.00% for the CinS2S2 library, and 0.028% and 2.35% for the CinS1S4 library. Using two single copy genes putatively implicated in somatic embryogenesis, screening of both libraries resulted in detection of 12 and 13 positive clones for each gene, in accordance with expected numbers.</p> <p>Conclusions</p> <p>This indicated that both BAC libraries are valuable tools for molecular studies in chicory, one goal being the positional cloning of the <it>S</it>-locus in this Asteraceae species.</p

Control of Gene Expression by the Retinoic Acid-Related Orphan Receptor Alpha in HepG2 Human Hepatoma Cells

Retinoic acid-related Orphan Receptor alpha (RORα; NR1F1) is a widely distributed nuclear receptor involved in several (patho)physiological functions including lipid metabolism, inflammation, angiogenesis, and circadian rhythm. To better understand the role of this nuclear receptor in liver, we aimed at displaying genes controlled by RORα in liver cells by generating HepG2 human hepatoma cells stably over-expressing RORα. Genes whose expression was altered in these cells versus control cells were displayed using micro-arrays followed by qRT-PCR analysis. Expression of these genes was also altered in cells in which RORα was transiently over-expressed after adenoviral infection. A number of the genes found were involved in known pathways controlled by RORα, for instance LPA, NR1D2 and ADIPOQ in lipid metabolism, ADIPOQ and PLG in inflammation, PLG in fibrinolysis and NR1D2 and NR1D1 in circadian rhythm. This study also revealed that genes such as G6PC, involved in glucose homeostasis, and AGRP, involved in the control of body weight, are also controlled by RORα. Lastly, SPARC, involved in cell growth and adhesion, and associated with liver carcinogenesis, was up-regulated by RORα. SPARC was found to be a new putative RORα target gene since it possesses, in its promoter, a functional RORE as evidenced by EMSAs and transfection experiments. Most of the other genes that we found regulated by RORα also contained putative ROREs in their regulatory regions. Chromatin immunoprecipitation (ChIP) confirmed that the ROREs present in the SPARC, PLG, G6PC, NR1D2 and AGRP genes were occupied by RORα in HepG2 cells. Therefore these genes must now be considered as direct RORα targets. Our results open new routes on the roles of RORα in glucose metabolism and carcinogenesis within cells of hepatic origin

Mise en place de référentiels morphologiques du développement de la fleur et de la graine chez la chicorée (Cichorium intybus L., Asteraceae)

Dans le but de fournir une base de référence utile pour les études relatives au développement de la fleur et de la graine chez Cichorium intybus, le développement normal de la fleur, de l akène et de la graine a été analysé histologiquement. A l aide du référentiel établi pour le développement floral normal, nous avons pu montrer que la stérilité mâle nucléaire de type Edith observée chez la chicorée est associée à des perturbations dans les cellules du tapis et de la couche moyenne ainsi qu à une dégénérescence des microspores qui a lieu après la formation des tétrades méiotiques. Les ressemblances histologiques entre le mâle stérile Edith avec certains mutants d Arabidopsis thaliana et du riz ont servi dans le choix de gènes candidats lors de l étude moléculaire de cette stérilité mâle. D autre part, la stérilité mâle cytoplasmique nommée 524 créée par fusion de protoplastes de tournesol mâle stérile et de chicorée fertile, a aussi été analysée histologiquement. Lors du développement floral chez le mâle stérile 524 , la dégénérescence des microspores commence avant la première mitose pollinique, si bien qu à l anthèse les grains de pollen sont vides; l anthère reste indéhiscente et ratatinée et les parois des cellules de l endothécium n ont pas l épaississement lignifié caractéristique de ce tissu. Par ailleurs, la caractérisation morphologique du développement floral chez les plantes portant le cytoplasme 524 nous a permis de mettre en évidence l existence d un mécanisme de restauration de la fertilité mais dont la nature génétique reste à déterminer. Pour le développement de l akène et de la graine, la chronologie des événements ainsi que la caractérisation morphologique et physiologique des différents stades du développement de l akène et de la graine ont révélé l existence d une variabilité génétique pour la durée du développement de l akène et la graine chez la chicorée. Le référentiel du développement de l akène et de l embryon zygotique pourra servir notamment aux analyses d expression des gènes candidats qui ont été identifiés pendant les études antérieures sur l embryogenèse somatique chez la chicorée.In order to provide a useful reference for morphological studies on flower and seed development in Cichorium intybus, the normal development for these two organs was histologically characterised. With reference to the morphological events during normal flower development, we have shown that nuclear male sterility type "Edith" is associated with disturbances in the tapetum and middle layer cells as well as degeneration of microspores after the formation of meiotic tetrads. Histological resemblance with some mutants in Arabidopsis thaliana and in rice helped for selection of candidate genes for molecular analysis of this male sterility. Moreover, the cytoplasmic male sterility named "524" which was created by fusion of protoplasts from sunflower male sterile and from fertile chicory was also histologically characterised. During flower development in the male sterile 524 degeneration of pollen grains occurs at the first pollen mitosis, so that at anthesis, the pollen grains are empty; the anther locules are unopened and shrivelled and no lignified secondary thickenings are observed in endothecium. Moreover, morphological characterisation of flower development in plants carrying the cytoplasm 524 led us to demonstrate the existence of a mechanism of fertility restoration for which heredity needs to be investigated. For the achene and seed development, the timing of events and morphological and physiological characterisation of developmental stages revealed genetic variability in the duration of achene and seed development in chicory. The reference established for achene and zygotic embryo development will help more particularly analysing expression of genes which have been previously shown to be involved in the somatic embryogenesis process in chicory.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Death, nasomaxillary complex and sleep in young children

Abstract This is an investigation of anatomical and sleep history risk factors that were associated with abrupt sleepassociated death in seven children with good pre-mortem history. Seven young children with abrupt deaths and information on health status, sleep history, death scene report, and autopsy performed in a specialized unit dedicated to investigation of abrupt death in young children were investigated Seven age and gender matched living children with obstructive-sleep-apnea (OSA) were compared to the findings obtained from the dead children. Two deaths results from accidents determined by the death scene and five were unexplained at the death scene. History revealed presence of chronic indicators of abnormal sleep in all cases prior death and history of an acute, often mild, rhinitis just preceding death in several. Four children, including three infants, were usually sleeping in a prone position. Autopsy demonstrated variable enlargement of upper airway soft tissues in all cases, and in all cases, there were features consistent with a narrow, small nasomaxillary complex, with or without mandibular retroposition. All children were concluded to have died of hypoxia during sleep. Our OSA children presented similar complaints and similar facial features. Anatomic risk factors for a narrow upper airway can be determined early in life, and these traits are often familial. Their presence should lead to greater attention to sleep-related complaints that may be present very early in life and indicate impairment of well been and presence of sleep disruption. Further investigation should be performed to understand the role of upper airway infection in the setting of anatomically small airway in apparently abrupt death of infants and toddlers

Death, nasomaxillary complex and sleep in young children

Abstract This is an investigation of anatomical and sleep history risk factors that were associated with abrupt sleepassociated death in seven children with good pre-mortem history. Seven young children with abrupt deaths and information on health status, sleep history, death scene report, and autopsy performed in a specialized unit dedicated to investigation of abrupt death in young children were investigated Seven age and gender matched living children with obstructive-sleep-apnea (OSA) were compared to the findings obtained from the dead children. Two deaths results from accidents determined by the death scene and five were unexplained at the death scene. History revealed presence of chronic indicators of abnormal sleep in all cases prior death and history of an acute, often mild, rhinitis just preceding death in several. Four children, including three infants, were usually sleeping in a prone position. Autopsy demonstrated variable enlargement of upper airway soft tissues in all cases, and in all cases, there were features consistent with a narrow, small nasomaxillary complex, with or without mandibular retroposition. All children were concluded to have died of hypoxia during sleep. Our OSA children presented similar complaints and similar facial features. Anatomic risk factors for a narrow upper airway can be determined early in life, and these traits are often familial. Their presence should lead to greater attention to sleep-related complaints that may be present very early in life and indicate impairment of well been and presence of sleep disruption. Further investigation should be performed to understand the role of upper airway infection in the setting of anatomically small airway in apparently abrupt death of infants and toddlers

Autopsie pédiatrique

Le consentement éclairé est un élément clef de la relation médecin-patient. L' autopsie, acte portant atteinte à l' intégrité du corps humain, nécessite un tel consentement de la part des parents. La difficulté pour le pathologiste réside dans le fait que ce n'est pas lui qui donne l' information et recueille le consentement pour l'acte qu' il va effectuer : il ne sait donc pas ce qui a été dit aux parents ni ce à quoi ils ont réellement consentis. Nous avons posé 2 questions : "Que savent les pédiatres de l' autopsie ?" pour savoir quelle information ils donnent aux parents, et "Quel doit être le devenir des tissus et organes prélevés lors d'une autopsie ?" pour connaitre le sentiment des parents. Des questionnaires ont été envoyés : à des pédiatres, et à des parents qui avaient consenti à l' autopsie de leur enfant. Les réponses ont montré que les pédiatresPARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Amélioration et contrôle de la qualité de chicorées mâles stériles cytoplasmsiques à cytoplasme 41.1

La stérilité mâle cytoplasmique (cms) se caractérise par une incapacité à produire des grains de pollen fonctionnels, ce qui permet d'éviter l'autofécondation. Elle présente une hérédité maternelle. Chez la chicorée, la cms a été obtenue par fusion de protoplastes avec le tournesol mâle stérile (ms). L'utilisation des chicorées ms à cytoplasme 41.1 pour la création des variétés hybrides révèle une déficience au niveau du rendement pour les hybrides produits ainsi que des événements de chlorose, en particulier dans des conditions climatiques extrêmes. La fertilité mâle n'est pas toujours le seul caractère touché par les mutations mitochondriales. Il existe des effets pléiotropes affectant d'autres métabolismes comme la photosynthèse. Afin de pallier cette déficience, nous avons réalisé de nouvelles fusions entre des protoplastes de chicorées industrielles fertiles et mâles stériles, de façon à remanier le génome mitochondrial des chicorées ms ; nous avons également créé une nouvelle source de mâle stérilité de la chicorée par fusion entre des protoplastes de chicorées industrielles et de chicorées frisées, toutes deux fertiles. La caractérisation physiologique de la stérilité mâle cytoplasmique 41.1 des chicorées montre que ces plantes, bien que présentant des rendements agronomiques souvent légèrement inférieurs à ceux des plantes fertiles, ne peuvent pas être considérées comme déficientes puisque les variations observées ne sont pas statistiquement significatives. L'exploration du protéome mitochondrial de ces chicorées ms a permis de révéler une modulation de l'expression du complexe F0F1-ATPase avec une diminution de son expression chez les plantes ms.LILLE1-BU (590092102) / SudocSudocFranceF