Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients

<p>Abstract</p> <p>Background</p> <p>The presence of HIV-1 preintegration reservoir was assessed in an <it>in vitro </it>experimental model of latent HIV-1 infection, and in patients treated or not with highly active antiretroviral therapy (HAART).</p> <p>Results</p> <p>In resting CD4⁺T lymphocytes latently infected <it>in vitro </it>with HIV-1, we demonstrated that the polyclonal activation induced a HIV-1 replication, which could be prevented by the use of an HIV-1 integrase inhibitor. We also showed that this reservoir was labile since the rescuable HIV-1-antigens production from unintegrated HIV-1 genomes declined over time. These data confirm that our experimental approach allows the characterization of a functional unintegrated HIV-1 reservoir. We then explored the preintegration reservoir in HIV-1-infected patients. This reservoir was detected in 11 of 12 untreated patients, in 4 of 10 sustained responders to HAART, and in one incomplete responder. This reservoir was also inducible, labile, and anti-HIV-1 integrase drug inhibited its induction. Finally, this reservoir was associated with the presence of spontaneous HIV-1 antigens producing CD4⁺T cells in blood from 3 of 3 untreated patients and 2 of 2 sustained responders to HAART harboring a preintegration reservoir.</p> <p>Conclusion</p> <p>This preintegration phase of HIV-1 latency could be a consequence of the ongoing viral replication in untreated patients and of a residual viral replication in treated patients.</p

The Cellular Processing Capacity Limits the Amounts of Chimeric U7 snRNA Available for Antisense Delivery

Many genetic diseases are induced by mutations disturbing the maturation of pre-mRNAs, often affecting splicing. Antisense oligoribonucleotides (AONs) have been used to modulate splicing thereby circumventing the deleterious effects of mutations. Stable delivery of antisense sequences is achieved by linking them to small nuclear RNA (snRNAs) delivered by viral vectors, as illustrated by studies where therapeutic exon skipping was obtained in animal models of Duchenne muscular dystrophy (DMD). Yet, clinical translation of these approaches is limited by the amounts of vector to be administered. In this respect, maximizing the amount of snRNA antisense shuttle delivered by the vector is essential. Here, we have used a muscle- and heart-specific enhancer (MHCK) to drive the expression of U7 snRNA shuttles carrying antisense sequences against the human or murine DMD pre-mRNAs. Although antisense delivery and subsequent exon skipping were improved both in tissue culture and in vivo, we observed the formation of additional U7 snRNA by-products following gene transfer. These included aberrantly 3′ processed as well as unprocessed species that may arise because of the saturation of the cellular processing capacity. Future efforts to increase the amounts of functional U7 shuttles delivered into a cell will have to take this limitation into account

Les TICE et les jeunes enseignants : les représentations en formation initiale

La question du rapport des jeunes enseignants en formation initiale avec les « nouvelles technologies » demeure une question vive tant il est vrai que les usages de ce qu'il est convenu d'appeler les « TICE » en milieu scolaire restent rares. De nombreuses questions se posent encore au sujet de l'utilisation des TICE par les enseignants. Est-il vrai par exemple, comme on le dit souvent, que les jeunes sont plus ouverts que leurs aînés aux nouvelles technologies ? Les IUFM sont-ils des centres d'innovation ou de diffusion de ce point de vue ? Parviennent-ils à banaliser les usages ? Deux ans après le « Plan d'urgence » quels en étaient les résultats ? Peut on percevoir des évolutions sensibles sur une si courte période ? Et enfin, les stagiaires de mathématiques ont-ils une attitude particulière vis à vis des TICE ? C'est pour tenter d'apporter quelques éléments de réponses à ces questions que deux enquêtes ont été menées auprès d'étudiants de seconde année de l'IUFM de Reims en 2000 et 2001. Cette communication détaille les résultats de ces enquêtes et fournit quelques pistes de réflexion sur la formation aux TICE à l'IUFM

De la polyvalence formelle à la polyvalence réelle : une enquête nationale sur les pratiques profession­nelles des enseignants du premier degré

From a formal point of view, primary teachers are supposed to be polyvalent i.e. to teach the whole range of subjects that constitute the curriculum of the pupils at their charge. Actually, teachers often call for outside contributors, a situation which tends to reduce their polyvalence. The present article affords the results of a nationally wide inquiry designed to evaluate the gap between the formally requested polyvalence and the actual one : it shows that more than a half of primary teachers recognize that they don't teach all the subject matters by themselves. The higher the grade, the more frequent this situation appears. It does not depend on personal characteristics of teachers but rather on contextual variables such as the school dimension and its localization : exchanges between teachers are more frequent in large and urban schools. French language and mathematics are the subject matters in which the teachers are most involved. Sports, music, and foreign language are the subject matters they most often hand over, not only to their colleagues but also to non-teachers When the teacher is alone, the schedules in these subject matters are below the requested ones. Outside contributions normalize this situation, except for the sports.D'un point de vue formel, les enseignants du premier degré sont supposés être polyvalents, c'est-à-dire enseigner aux élèves qu'ils ont en charge l'ensemble des matières au programme de l'école primaire. On sait cependant qu'aujourd'hui ces enseignants font souvent appel à des contributions ou intervenants extérieurs, ce qui tend à réduire leur polyvalence. Cet article présente les résultats d'une enquête nationale qui visait à évaluer les écarts entre polyvalence formelle et polyvalence réelle. Il montre que plus de la moitié des enseignants reconnaissent qu'ils n'enseignent pas eux-mêmes l'ensemble des domaines. Cette situation augmente d'autant plus que l'âge des élèves s'élève. Elle ne dépend pas des caractéristiques personnelles des enseignants mais plutôt de variables contextuelles telles que la dimension de l'école et sa localisation : les échanges entre enseignants sont plus fréquents dans les écoles urbaines importantes. L'enseignement du français ainsi que celui des mathématiques sont les domaines dans lesquels les enseignants s'impliquent le plus, tandis que l'EPS, la musique et les langues vivantes sont les plus délaissées et les plus fréquemment déléguées non seulement à des collègues mais aussi à des non enseignants. Dans ces disciplines lorsque le maître enseigne seul, les horaires sont inférieurs aux horaires recommandés dans les 10. Le recours à des intervenants extérieurs normalise cette situation, à l'exception cependant de l'EPS.Baillat Gilles, Espinoza Odile, Vincent Jean. De la polyvalence formelle à la polyvalence réelle : une enquête nationale sur les pratiques profession­nelles des enseignants du premier degré. In: Revue française de pédagogie, volume 134, 2001. Situations de handicaps et institution scolaire. pp. 123-136

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-0

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>HIV-1 integrase inhibitor L-731,988 at the final concentration of 40 μM. . To assess the correlation between the unintegrated HIV-1 DNA decay and the decline of rescuable viral production, infected resting CD4T cells were preincubated 1 or 2 days before polyclonal stimulation. In both cases, in order to prevent infection of others cells by -synthesized HIV-1, 1 μg/ml of the viral entry inhibitor T20 was also added in culture medium

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-3

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>umerated at the end of culture. The median values are shown as black bars

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-4

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>re preincubated one or two days before their polyclonal activation. A gate was set on the forward-scatter vs side-scatter histogram. As shown on different histograms, gate corresponded to CD69CD4T lymphocytes. The analysis of the 7AAD level expression demonstrated that activated CD4T lymphocytes were viable cells