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L’asthme est une pathologie respiratoire chronique et fréquente affectant aussi bien les enfants que les adultes. Dans sa forme sévère, l’asthme est caractérisé notamment par des exacerbations, le plus souvent dues à une infection par un rhinovirus. Selon plusieurs études épidémiologiques, le rôle du rhinovirus A (RVA) et C (RVC) dans les exacerbations est différent entre les enfants et les adultes. En effet, le RVA est majoritairement responsable des exacerbations de l’asthme chez l’adulte alors que le RVC est plus largement impliqué dans les exacerbations les plus sévères de l’enfant. Cette spécificité liée à l’âge suggère une modification physiopathologique de l’épithélium bronchique d’enfants par rapport à celui de l’adulte. Cependant, l’étude de l’infection épithéliale par le RVA et le RVC se heurte à des difficultés techniques, notamment au niveau de la production des particules de RVC infectieuses, mais aussi dans la visualisation de l’infection par le rhinovirus dans un modèle d’épithélium différencié en interface air–liquide. Ainsi, l’objectif de cette étude est de développer un modèle d’étude in vitro d’infection par le rhinovirus A et C dans un modèle d’épithélium permettant l’étude de la cinétique d’infection des épithéliums d’adultes et d’enfants.

Few empirical data address naturalistic outcomes of residential eating disorder (ED) treatment. Study aims were to evaluate course, effectiveness, and predictors of outcome in a residential treatment program. We evaluated 80 consecutively admitted female adolescents with the SCID-IV. Primary outcomes were treatment completion, subsequent readmission, clinical global impressions, and changes in body weight. Mean length of stay was 51 days, and 80% of patients were discharged according to treatment plans. Mean expected body weight (EBW) for AN patients increased from 80% to 91%. Patients reported significant improvements in ED symptoms, depression, and quality of life. Low admission %EBW and previous psychiatric hospitalizations were associated with premature termination. Overall, findings support that residential treatment is largely acceptable to patients, and that residential care may provide an opportunity for substantive therapeutic gains.

To assess the feasibility of using the renin promoter for expressing Cre recombinase in juxtaglomerular (JG) cells only, we generated five independent transgenic mouse lines (designated hRen-Cre) expressing Cre recombinase under control of a 12.2-kb human renin promoter. In the kidneys of adult mice Cre mRNA (RT-PCR) was found in the renal cortex, with Cre protein (immunohistochemistry) being localized in afferent arterioles and to a lower degree in interlobular arteries. Cre mRNA levels were regulated in a renin-typical fashion by changes in oral salt intake, water restriction, or isoproterenol infusion, indicating the presence of key regulatory elements within 12.2 kb of the 5′-flanking region of the human renin gene. hRen-Cre mice were interbred with both the ROSA26-EGFP and ROSA26-lacZ reporter strains to assess renin promoter activity from Cre-mediated excision of a floxed stop cassette and subsequent enhanced green fluorescent protein (EGFP) and β-galactosidase (β-gal) detection. In adult mice, β-gal staining and EGFP were observed in afferent arterioles and interlobular arteries, overlapping with Cre protein expression. In addition, intense β-gal staining was found in cortical and medullary collecting ducts where Cre expression was minimal. In embryonic kidneys, β-gal staining was detected in the developing collecting duct system beginning at embryonic day 12, showing substantial activity of the human renin promoter in the branching ureteric bud. Our data indicate that besides its well-known activity in JG cells and renal vessels the human renin promoter is transiently active in the collecting duct system during kidney development, complicating the use of this approach for JG cell-specific excision of floxed targets.

We have investigated the regulation of the activin-inducible distal element (DE) of the Xenopus goosecoid promoter. The results show that paired-like homeodomain transcription factors of the Mix family, Mixer and Milk, but not Mix.1, mediate activin/TGF-beta-induced transcription through the DE by interacting with the effector domain of Smad2, thereby recruiting active Smad2/Smad4 complexes to the Mixer/Milk-binding site. We identify a short motif in the carboxyl termini of Mixer and Milk, which is demonstrated to be both necessary and sufficient for interaction with the effector domain of Smad2 and is required for mediating activin/TGF-beta-induced transcription. This motif is not confined to these homeodomain proteins, but is also present in the Smad2-interacting winged-helix proteins Xenopus Fast-1, human Fast-1, and mouse Fast-2. We demonstrate directly that transcription factors of different DNA-binding specificity recruit activated Smads to distinct promoter elements via a common mechanism. These observations, together with the temporal and spatial expression patterns of Mixer and Milk, lead us to propose a model for mesoendoderm formation in Xenopus in which these homeodomain transcription factor/Smad complexes play a role in initiating and maintaining transcription of target genes in response to endogenous activin-like signals.

AbstractThe Dominion Radio Astrophysical Observatory (DRAO) is carrying out a survey as part of an international collaboration to image the northe, at a common resolution, in emission from all major constituents of the interstellar medium; the neutral atomic gas, the molecular gas, the ionised gas, dust and relativistic plasma. For many of these constituents the angular resolution of the images (1 arcmin) will be more than a factor of 10 better than any previous studies. The aim is to produce a publicly-available database of high resolution, high-dynamic range images of the Galaxy for multi-phase studies of the physical states and processes in the interstellar medium. We will sketch the main scientific motivations as well as describe some preliminary results from the Canadian Galactic Plane Survey/Releve Canadien du Plan Galactique (CGPS/RCPG).

Renin catalyzes the rate-limiting step of the renin-angiotensin system, which regulates blood pressure and electrolyte homeostasis. To determine cell-specific human renin gene control elements, the transcriptional activity of promoter regions up to position -8876 was studied in renin-expressing cells. A positive regulatory region conferring approximately 57-fold higher transcriptional activity to the human renin gene promoter in chorionic cells was identified between nucleotides -5777 and -5552. It had the orientation-independent activity typical of classical enhancers. It also conferred approximately 59-fold higher transcriptional levels from the heterologous simian virus 40 (SV40) promoter in chorionic cells and approximately 6-fold higher transcriptional levels in Calu-6 and As4.1 cells, whereas no effect was measured in non-renin-expressing cells. DNase I footprinting showed that this enhancer contains three binding sites for chorionic cell nuclear extracts. Functional analysis suggested that the activity of the enhancer is regulated by differential mechanisms in the three renin-expressing cells involving a complex arrangement of AP-1 motifs binding cell-specific members of the basic leucine zipper family of transcription factors. Thus, our results demonstrate that this enhancer plays a key role in the expression of the human renin gene in the chorion and may also be involved in its regulated expression in other tissues.

To delineate the cis-acting elements of the proximal promoter responsible for cAMP-induced human renin gene transcription, 5'-flanking regions of the human renin gene were fused to a luciferase reporter gene and transfected in chorionic cells. Forskolin treatment induced the expression of luciferase by 2.4 fold when the reporter plasmid contained the promoter region (-582 to +16). Mutation or deletion of the CRE diminished (1.7 fold) but did not abolish cAMP-induced transcription, demonstrating that region containing the CRE and region containing a Pit-1 site were both necessary for cAMP maximal induction. Taken together, these results show that the cAMP response of the human renin gene may involve CREB binding the CRE and tissue-specific factors (from chorionic and kidney cell origin), different from Pit-1, that interact with the Pit-1 response DNA elements.

La matrice extra-cellulaire (MEC) est une structure dynamique composée à plus de 90 % de collagènes, qui influence la progression tumorale et l’apparition de métastases. Son rôle dans l’agressivité des phéochromocytomes et paragangliomes (PPGL) est inconnu.

En garantissant une qualité irréprochable de l’ensemble des techniques de préparation du prélèvement, le technicien en anatomie et cytologie pathologique (ACP) a un rôle central et indispensable pour permettre l’établissement d’un diagnostic. Devant le développement de la spécialité, son rôle évolue. Pour accompagner ces changements, un groupe de techniciens s’est structuré en Midi-Pyrénées sous l’égide du réseau régional de cancérologie ONCOMIP. Un groupe de travail, composé d’une vingtaine de techniciens volontaires issus de laboratoires ACP publics et privés de la région, a été mis en place en 2013.