Akt fosforila FoxG1 en cèl·lules de glioma

En un treball recent s’ha descrit l’amplificació del gen del factor de transcripció FoxG1, homòleg de l'oncogen víric aviar Qin, en mostres de meduloblastoma, un tipus de tumor cerebral que representa el 20% dels tumors cerebrals infantils malignes (Adesina et al.¸2007). El tumor cerebral més freqüent i agressiu en l’adult és el glioma, especialment la seva forma més maligna: el glioblastoma multiforme (glioma de grau IV segons la classificació de l'OMS). En aquest treball hem estudiat l'expressió proteica del factor de transcripció FoxG1, homòleg de l'oncogen víric aviar Qin, en mostres de glioma. Vam analitzar 15 mostres de glioma, detectant FoxG1 en 9 d’elles, i amb diferents nivells d’expressió. Intentant aprofundir en el coneixement de la funció i la regulació de FoxG1, vam estudiar si FoxG1 podia ser fosforilat. Vam detectar, tant per assaig cinasa com per espectrometria de masses, que FoxG1 és un substracte directe de la cinasa Akt, el principal efector de la via de PI3K (phosphoinositide 3-kinase). En la línia cel•lular de glioblastoma U373MG, vam observar que Akt endogen fosforila FoxG1 en un pèptid situat a l’extrem C-terminal del domini forkhead. Aquesta fosforilació és contrarestada per un inhibidor farmacològic de PI3K. Al contrari del que passa en FoxO on la fosforilació per Akt inhibeix l’activitat de FoxO promovent la seva exportació del nucli, la fosforilació de FoxG1 per Akt no promou cap canvi en la seva localització subcel•lular, i FoxG1 es manté nuclear. Actualment estem estudiant els efectes biològics de la fosforilació de FoxG1 per Akt.

Sex-dependent selection on an autosomal melanic female ornament promotes the evolution of sex ratio bias.

Sex-dependent selection often leads to spectacularly different phenotypes in males and females. In species in which sexual dimorphism is not complete, it is unclear which benefits females and males derive from displaying a trait that is typical of the other sex. In barn owls (Tyto alba), females exhibit on average larger black eumelanic spots than males but members of the two sexes display this trait in the same range of possible values. In a 12-year study, we show that selection exerted on spot size directly or on genetically correlated traits strongly favoured females with large spots and weakly favoured males with small spots. Intense directional selection on females caused an increase in spot diameter in the population over the study period. This increase is due to a change in the autosomal genes underlying the expression of eumelanic spots but not of sex-linked genes. Female-like males produced more daughters than sons, while male-like females produced more sons than daughters when mated to a small-spotted male. These sex ratio biases appear adaptive because sons of male-like females and daughters of female-like males had above-average survival. This demonstrates that selection exerted against individuals displaying a trait that is typical of the other sex promoted the evolution of specific life history strategies that enhance their fitness. This may explain why in many organisms sexual dimorphism is often not complete.

The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: trauma and early psychotic mania.

OBJECTIVE: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. METHODS: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. RESULTS: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect. CONCLUSIONS: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.

L'apôtre, père et mère de la communauté (1 Th 2,1-12)

La correspondance paulinienne réserve, dans ses passages oubliés, quelques surprises propres à nous faire réviser une image figée de Paul. Ainsi 1 Th 2/1-12, où l'apôtre présente son investissement dans la mission sous la double figure de la mère et du père. Daniel MARGUERAT montre que le vocabulaire affectif afflue dans ce texte où Paul appelle les chrétiens de Thessalonique à identifier dans leur histoire personnelle les traces de la puissance de l'évangile. Conscience collective de l'apostolat et lecture théologique des relations interpersonnelles constituent deux accents forts de ce plus ancien écrit de l'apôtre de Tarse.

L'évasion de Pierre et la mort du tyran (Actes 12): un jeu d'échos intertextuels

(Résumé de l'ouvrage) La Bible restitue au lecteur des écrits qui n'y figurent parfois pas explicitement, mais qui ont baigné les auteurs jusqu'à ressortir quasi intacts dans les textes canoniques. Tout texte appelle donc à la mémoire du lecteur d'autres textes, et, dans la Bible, leur identification reste pour l'heure relativement difficile à effectuer. Les auteurs de cet ouvrage ont l'ambition de fournir et d'illustrer une méthode pour identifier l'héritage littéraire dont la Bible se fait le témoin. Que ce soit sur l'Ancien Testament, le Nouveau Testament ou les textes apocryphes, les contributions s'attachent à exposer des relations de co-présence entre deux ou plusieurs textes (par le biais de la citation, de la référence ou de l'allusion) ou la relation de dérivation d'un texte à un autre.

De la loi comme prétexte. Tours et détours d'une allusion dans le débat exilique sur la royauté en 1Samuel 8-12.

(Résumé de l'ouvrage) La Bible restitue au lecteur des écrits qui n'y figurent parfois pas explicitement, mais qui ont baigné les auteurs jusqu'à ressortir quasi intacts dans les textes canoniques. Tout texte appelle donc à la mémoire du lecteur d'autres textes, et, dans la Bible, leur identification reste pour l'heure relativement difficile à effectuer. Les auteurs de cet ouvrage ont l'ambition de fournir et d'illustrer une méthode pour identifier l'héritage littéraire dont la Bible se fait le témoin. Que ce soit sur l'Ancien Testament, le Nouveau Testament ou les textes apocryphes, les contributions s'attachent à exposer des relations de co-présence entre deux ou plusieurs textes (par le biais de la citation, de la référence ou de l'allusion) ou la relation de dérivation d'un texte à un autre.

Comparison of purified 12 kDa and recombinant 15 kDa Fasciola hepatica antigens related to a Schistosoma mansoni fatty acid binding protein

Vaccines in schistosomiasis using homologous antigens have been studied extensively in experimentally infected mammalian hosts. Vaccines using heterologous antigens have received comparatively less attention. This review summarizes recent work on a heterologous 12 kDa Fasciola hepatica antigenic polypeptide which cross reacts with Schistosoma mansoni. A cDNA has been cloned and sequenced, and the predicted amino acid sequence of the recombinant protein has been shown to have significant (44) identity with a 14 kDa S. mansoni fatty acid binding protein. Thus in the parasitic trematodes fatty acid binding proteins may be potential vaccine candidates. The F. hepatica recombinant protein has been overexpressed and purified and denoted rFh15. Preliminary rFh15 migrates more slowly (i.e. may be slightly larger) than nFh12 on SDS-PAGE and has a predicted pI of 6.01 vs. observed pI of 5.45. Mice infected with F. hepatica develop antibodies to nFh12 by 2 weeks of infection vs. 6 weeks of infection to rFh15; on the other hand, mice with schistosomiasis mansoni develop antibodies to both nFh12 and rFh15 by 6 weeks of infection. Both the F. hepatica and S. mansoni cross-reactive antigens may be cross-protective antigens with the protection inducing capability against both species.

Emotional reactivity at 12 months in very preterm infants born at <29 weeks of gestation.

The present study evaluated the socio-emotional development of very preterm born infants at 12 months corrected age. Forty-one infants born very preterm (<29 weeks of gestation) were compared to 22 infants born full term on a standardized behavioral assessment and a parental temperament questionnaire, both measuring emotional reactivity to joy, anger and fear, as well as sustained attention. The behavioral assessment showed that very preterm infants exhibited as much joy as full term infants during a joy-eliciting episode. However, they expressed a significantly higher reactivity in anger-eliciting situations and a reduced reactivity toward fear-eliciting situations. For all three emotion-eliciting situations, the preterm infants reacted with a higher level of motor activity. The preterm infants also exhibited a distinct attention pattern with a significantly higher initial attention level which declined rapidly throughout the episode. The questionnaire did not show any group differences. The clinical relevance of these results in terms of preliminary hallmarks of later behavioral difficulties such attention deficit/hyperactivity disorder are discussed as well as the inconsistencies observed between the questionnaire and the behavioral assessment.