Caractérisation fonctionnelle du gène AP1S1 mutant associé au syndrome de MEDNIK

Dans les cellules eucaryotes, le trafic intracellulaire de nombreuses protéines est assuré par des vésicules de transport tapissées de clathrine. Les complexes adaptateurs de clathrine (AP) sont responsables de l’assemblage de ces vésicules et de la sélection des protéines qui seront transportées. Nous avons étudié cinq familles atteintes du syndrome neurocutané MEDNIK qui est caractérisé par un retard mental, une entéropathie, une surdité, une neuropathie périphérique, de l’icthyose et de la kératodermie. Tous les cas connus de cette maladie à transmission autosomique récessive sont originaires de la région de Kamouraska, dans la province de Québec. Par séquençage direct des gènes candidats, nous avons identifié une mutation impliquant le site accepteur de l’épissage de l’intron 2 du gène codant pour la sous-unité σ1 du complexe AP1 (AP1S1). Cette mutation fondatrice a été retrouvée chez tous les individus atteints du syndrome MEDNIK et altère l’épissage normal du gène, menant à un codon stop prématuré. Afin de valider l’effet pathogène de la mutation, nous avons bloqué la traduction de cette protéine chez le poisson zébré en injectant une séquence d’oligonucléotides antisenses spécifique à AP1S1. À 48 heures après la fertilisation, les larves knock down pour AP1S1 montrent une réduction de la pigmentation, une désorganisation de la structure de l’épiderme et une perturbation du développement moteur. Alors que la surexpression de l’AP1S1 humain dans ce modèle a permis la récupération du phénotype normal, l’expression de l’AP1S1 mutant fut sans effet sur les phénotypes moteurs et cutanés des larves knock down. Les résultats obtenus montrent que la mutation du AP1S1 responsable du syndrome de MEDNIK est associée à une perte de fonction et que la sous-unité σ1 du complexe AP1 joue un rôle crucial dans l’organisation de l’épiderme et le développement de la moelle épinière.Intracellular protein transport between organelles is mainly mediated by clathrin coated vesicles. Clathrin adaptor protein (AP) complexes participate in clathrin coated vesicle formation and in sorting protein cargo. We studied 5 families with MEDNIK syndrome, which is characterized by mental retardation, enteropathy, deafness, neuropathy, ichtyosis and keratoderma. All families affected with this autosomal recessive syndrome originate from an isolated population in the Kamouraska region of Quebec. The candidate genes identified in the positive region were sequenced and a founder mutation was identified in the acceptor splice slice of intron 2 of the AP1S1 gene. This gene encodes for the small subunit σ1 of the complex adaptor 1 (AP1). This splicing mutation leads to a premature stop codon, which is predicted to alter the normal function of this protein. To validate the pathogenic effect of this mutation we blocked the AP1S1 protein translation in zebrafish by injecting an anti-sense oligonucleotide designed against AP1S1. At 48 hours post fertilisation, the knockdown larvae showed reduced pigmentation, perturbation of skin formation, and severe perturbation of motor development and function motor development. Over expression of the human AP1S1 rescued the normal phenotype whereas the expression of the mutant AP1S1 did not. These results show that this mutation is causative for MEDNIK syndrome and demonstrates a critical role of the small subunit σ1 in epidermal organisation and in the development of the spinal cord

Évaluation de la vitesse d'absorption de boissons spéciales (de récupération)

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

L'aménagement du territoire axé sur les transports en commun : le cas de la ligne de train de banlieue Montréal/Blainville

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

A single mutation in the mammalian orthoreovirus S1 gene is responsible for increased interferon sensitivity in a virus mutant selected in Vero cells

In a previous study, a mammalian orthoreovirus mutant was isolated based on its increased ability to infect interferon-defective Vero cells and was referred to as Vero-cellsadapted virus (VeroAV). This virus exhibits reduced ability to resist the antiviral effect of interferon. In the present study, the complete genome sequence of VeroAV was first determined. Reverse genetics was then used to identify a unique mutation on the S1 gene, overlapping the σ1 and σ1s reading frame, resulting in increased sensitivity to interferon. A virus lacking σ1s expression consecutive to mutation of its initiation codon was then shown to exhibit a further increase in sensitivity to interferon, supporting the idea that σ1s is the viral protein responsible. This identification of a new determinant of reovirus sensitivity to interferon gives credentials to the idea that multiple reovirus genes are responsible for the level of interferon induction and susceptibility to the interferon-induced antiviral activities

Compositional and functional trajectories of herbaceous communities after deer density control in clear-cut boreal forests

Overabundant populations of large herbivores have strong persistent effects on forest composition, structure, and function. However, the mechanism through which plant communities recover their original composition and function after herbivore management remains poorly understood. We assessed the temporal trajectories of the herbaceous communities in Abies balsamea (L.) Mill. and Picea glauca (Moench) Voss stands on Anticosti Island (Quebec, Canada) over 8 years following clear-cutting and deer management. The impact of deer exclusion or reduction to 7.5 and 15 deer·km–2 was compared with benchmark in situ deer densities (27 and 56 deer·km–2). Effects of deer management treatments on plant species and functional trait assemblages over time were assessed using principal response curves. Although complete deer exclusion seemed necessary to modify species composition from that occurring under intense browsing, a reduced density of 7.5 deer·km–2 was sufficient to induce significant changes in functional trait assemblages of regenerating stands. For instance, reduced deer densities favored plants with brightly colored flowers and compound inflorescences pollinated by animals and producing large seeds and fleshy fruits dispersed by animals. We conclude that the boreal forest's herbaceous communities are resilient to chronic browsing when deer population reduction and forest clearcutting are applied in synergy.Les populations surabondantes de grands herbivores ont des effets majeurs et persistants sur la composition, la structure et le fonctionnement de la forêt. Toutefois, le mécanisme par lequel les communautés végétales retrouvent leur composition et leur fonctionnement originels en réponse au contrôle des herbivores demeure mal compris. Nous avons évalué les trajectoires temporelles des communautés herbacées dans des peuplements d'Abies balsamea (L.) Mill. et de Picea glauca (Moench) Voss à l'île d'Anticosti (Québec, Canada) pendant 8 années après avoir effectué une coupe à blanc et contrôlé les populations de cerfs. L'impact de l'exclusion du cerf ou d'une réduction de la densité à 7,5 ou 15 cerfs·km–2 a été comparé à des densités témoins in situ (27 et 56 cerfs·km–2). Les effets des traitements de gestion du cerf sur les espèces végétales et les assemblages de traits fonctionnels ont été évalués en fonction du temps au moyen de la méthode des courbes de réponses principales. Bien que l'exclusion complète du cerf ait semblé nécessaire pour modifier la composition spécifique par rapport à celle observée en conditions de broutage intense, une densité réduite à 7,5 cerfs·km–2 était suffisante pour induire des changements significatifs dans les assemblages de traits fonctionnels des peuplements en régénération. À titre d'exemple, des densités réduites de cerfs ont favorisé les plantes à fleurs de couleur vive et les plantes à fleurs composées pollinisées par les animaux et produisant de grosses graines et des fruits charnus dispersés par les animaux. Nous concluons que les communautés herbacées de la forêt boréale sont résilientes au broutage chronique quand une réduction des populations de cerfs et une coupe forestière à blanc sont appliquées en synergie

Developmental predictors of inattention-hyperactivity from pregnancy to early childhood

Objective The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers. Materials and Methods Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards). Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment) and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood). Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence.Results A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years. Discussion This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood

Star Formation in Sculptor Group Dwarf Irregular Galaxies and the Nature of "Transition" Galaxies

We present new H-alpha narrow band imaging of the HII regions in eight Sculptor Group dwarf irregular (dI) galaxies. Comparing the Sculptor Group dIs to the Local Group dIs, we find that the Sculptor Group dIs have, on average, lower values of SFR when normalized to either galaxy luminosity or gas mass (although there is considerable overlap between the two samples). The properties of ``transition'' (dSph/dIrr) galaxies in Sculptor and the Local Group are also compared and found to be similar. The transition galaxies are typically among the lowest luminosities of the gas rich dwarf galaxies. Relative to the dwarf irregular galaxies, the transition galaxies are found preferentially nearer to spiral galaxies, and are found nearer to the center of the mass distribution in the local cloud. While most of these systems are consistent with normal dI galaxies which currently exhibit temporarily interrupted star formation, the observed density-morphology relationship (which is weaker than that observed for the dwarf spheroidal galaxies) indicates that environmental processes such as ``tidal stirring'' may play a role in causing their lower SFRs.Comment: 35 pages, 10 figures, accepted for Feb 2003 AJ, companion to astro-ph/021117

Star Formation in Dwarf Galaxies of the Nearby Centaurus A Group

We present Halpha narrow-band imaging of 17 dwarf irregular galaxies (dIs) in the nearby Centaurus A Group. Although all large galaxies of the group have a current or recent enhanced star formation episode, the dIs have normal star formation rates and do not contain a larger fraction of dwarf starbursts than other nearby groups. Relative distances between dIs and larger galaxies of the group can be computed in 3D since most of them have now fairly accurately known distances. We find that the dI star formation rates do not depend on local environment, and in particular they do not show any correlation with the distance of the dI to the nearest large galaxy of the group. There is a clear morphology-density relation in the Centaurus A Group, similarly to the Sculptor and Local Groups, in the sense that dEs/dSphs tend to be at small distances from the more massive galaxies of the group, while dIs are on average at larger distances. We find four transition dwarfs in the Group, dwarfs that show characteristics of both dE/dSphs and dIs, and which contain cold gas but no current star formation. Interestingly the transition dwarfs have an average distance to the more massive galaxies which is intermediate between those of the dEs/dSphs and dIs, and which is quite large: 0.54 +- 0.31 Mpc. This large distance poses some difficulty for the most popular scenarios proposed for transforming a dI into a dE/dSph (ram-pressure with tidal stripping or galaxy harassment). If the observed transition dwarfs are indeed missing links between dIs and dE/dSphs, their relative isolation makes it less likely to have been produced by these mechanisms. We propose that an inhomogeneous IGM containing higher density clumps would be able to ram-pressure stripped the dIs at such large distances.Comment: 57 pages, 10 fi5gure

Species indicators of ecosystem recovery after reducing large herbivore density: Comparing taxa and testing species combinations

Indicator species have been used successfully for estimating ecosystem integrity, but comparative studies for defining optimal taxonomic group remain scarce. Furthermore, species combinations may constitute more integrative tools than single species indicators, but case studies are needed to test their efficiency. We used Indicator Species Analysis, which statistically determines the association of species to one or several groups of sites, to obtain indicators of ecosystem recovery after various deer density reductions. We used five taxonomic groups: plants, carabid beetles, bees, moths and songbirds. To test whether species combinations could complement single indicator species, we used plants as a model taxon and examined the indicator value of joint occurrence of two or three plant species. Our study relies on experimental controlled browsing enclosures established for six years on Anticosti Island (Quebec). Four levels of deer density (0, 7.5 and 15 deer km−2 and natural densities between 27 and 56 deer km−2) were studied in two vegetation cover types (uncut forests and cut-over areas), in a full factorial design for a total of eight experimental treatments. For all taxa but bees, we tested 54 treatment groups consisting in one specific density or in a sequence of two or more consecutive deer densities in one or both cover types (ten groups for bees, sampled only in cut-over areas). We found 12 plants, 11 moths and one songbird to be single species indicators of ecosystem conditions obtained under 12 different treatment groups. Six treatment groups were indicated by plants and six different ones by moths, of which one group was also identified by a songbird species. Moths were thus worth the extra sampling effort, especially since the groups they indicated were more treatment-specific (mainly one or two deer density treatments). We tested the same 54 treatment groups for plant species combinations represented by two or three co-occurring species. Plant combinations efficiently complemented plant singletons for detecting ecosystem conditions obtained under various deer densities. In fact, although singletons were highly predictive, 17 additional treatment groups were identified exclusively with two- and three-species combinations, some being more treatment-specific. Our findings show that plants and moths provide complementary indicators of ecosystem conditions under various deer densities, and that computing species combinations increases our capacity to monitor ecosystem recovery after reducing herbivore densities.Funding was provided by the Natural Sciences and Engineering Research Council of Canada (NSERC)-Produits forestiers Anticosti Industrial Chair to SDC, the Ministère des Ressources Naturelles et de la Faune du Québec, the Canadian Forest Service of Natural Resources Canada and an NSERC scholarship to MB and NSERC DG to MP and SP. We are grateful to the Centre de la Science de la Biodiversité du Québec and Centre d’études nordiques for scholarships

Chemical Abundances of Seven Irregular and Three Tidal Dwarf Galaxies in the M81 Group

We have derived nebular abundances for 10 dwarf galaxies belonging to the M81 Group, including several galaxies which do not have abundances previously reported in the literature. For each galaxy, multiple H \ii regions were observed with GMOS-N at the Gemini Observatory in order to determine abundances of several elements (oxygen, nitrogen, sulfur, neon, and argon). For seven galaxies, at least one H \ii region had a detection of the temperature sensitive [OIII] $\lambda$4363 line, allowing a "direct" determination of the oxygen abundance. No abundance gradients were detected in the targeted galaxies and the observed oxygen abundances are typically in agreement with the well known metallicity-luminosity relation. However, three candidate "tidal dwarf" galaxies lie well off this relation, UGC 5336, Garland, and KDG 61. The nature of these systems suggests that UGC 5336 and Garland are indeed recently formed systems, whereas KDG 61 is most likely a dwarf spheroidal galaxy which lies along the same line of sight as the M81 tidal debris field. We propose that these H \ii regions formed from previously enriched gas which was stripped from nearby massive galaxies (e.g., NGC 3077 and M81) during a recent tidal interaction.Comment: 37 pages, 10 figures, accepted for publication in ApJ. Slit positions in Table 2 have been update