How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity. Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007     

Protein kinases mediate nitric oxide-induced apoptosis in the insect cell line IPLB-LdFB

The involvement of protein kinases (PKA, PKC and PKB) in nitric oxide (NO)-induced apoptosis with sodium nitroprusside plus N-acetyl-L-cysteine in the IPLB-LdFB cell line from the insect Lymantria dispar was investigated. The presence of protein kinase-like molecules was demonstrated by western blot analysis. The role of the kinases in programmed cell death was analysed in cytofluorimetric experiments by incubating the insect cells with H-89 (a specific inhibitor of PKA), calphostin C (an inhibitor of PKC) or wortmannin (an inhibitor of phosphatidylinositol 3-kinase). The results show that PKA is correlated with the induction and PKC and PKB with the prevention of NO-induced insect cell death. Moreover, NO-induced apoptosis involves the release of cytochrome c. Received 15 March 2002; accepted 25 March 2002     

Existence of a reactive zone in the interrenal gland of reptiles

Resumen El estudio histofisiológico de la glándula interrenal de un lagarto teído (Cnemidophorus l. lemniscatus) permitió poner de manifiesto la que se denominó zona reactiva de la glándula. Por su situación es periférica, y está constituida por células dispuestas en formaciones redondeadas. Estas células, que tienen normalmente aspecto de menor actividad, responden más rápida e intensamente que las centrales a la acción de la corticotrofina, exógena o endógena, y aparecen entonces más activas que las últimas.     

The corticotroph cells of the anterior pituitary gland of a reptile:Cnemidophorus l. lemniscatus (sauria,teiidae)

Resumen Mediante la administration de metopirona pudo demostrarse en la hipófisis anterior deCnemidophorus l. lemniscatus la existencia de un tercer tipo de células secretoras no mucoprotidicas, responsables de la producción de corticotrofina y no identificadas hasta ahora en reptiles. Estas células se encuentran en la portión rostral del lóbulo y, en los animales testigos, resultan cromófobas con las coloraciones efectuadas. Por acción de la metopirona sufren considerable hipertrofia e hiperplasia y aparecen en su citoplasma gránulos gruesos y relativamente escasos que presentan moderada afinidad hacia la hematoxilina férrica.     

Early B lymphocytes in man

Summary We have confirmed in man the presence of a subpopulation of B lymphocytes which cannot reexpress their immunological receptors after challenge with antibodies. These early B lymphocytes were studied in peripheral blood, in cord blood and also, with anti-idiotypic sera, in the peripheral blood of a myeloma patient.Acknowledgments. This work was supported by CNR, Progetti finalizzati, Controllo della Crescita Neoplastica. We thank Prof. J. Urbain for helpful suggestions.     

Effect of partition coefficient on microsegregation during solidification of aluminium alloys

In the modeling of microsegregation, the partition coefficient is usually calculated using data from the equilibrium phase diagrams. The aim of this study was to experimentally and theoretically analyze the partition coefficient in binary aluminum-copper alloys. The samples were analyzed by differential thermal analysis (DTA), which were melted and quenched from different temperatures during solidification. The mass fraction and composition of phases were measured by image processing and scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectroscopy (EDS) unit. These data were used to calculate as the experimental partition coefficients with four different methods. The experimental and equilibrium partition coefficients were used to model the concentration profile in the primary phase. The modeling results show that the profiles calculated by the experimental partition coefficients are more consistent with the experimental profiles, compared to those calculated using the equilibrium partition coefficients.     

Revealing the world of RNA interference

The recent discoveries of RNA interference and related RNA silencing pathways have revolutionized our understanding of gene regulation. RNA interference has been used as a research tool to control the expression of specific genes in numerous experimental organisms and has potential as a therapeutic strategy to reduce the expression of problem genes. At the heart of RNA interference lies a remarkable RNA processing mechanism that is now known to underlie many distinct biological phenomena.     

Efficacy of some histochemical techniques for acid mucopolysaccharides

Résumé L'efficacité relative de certaines méthodes histochimiques utilisées habituellement pour la mise en évidence des mucopolysaccharides acides a été étudiée sur des peaux de rats soumises à des conditions expérimentales diverses. Les différentes concentrations des substances en étude étaient connues, ayant été quantitativement déterminées par la méthode chimique dePearce etWatson. La réaction métachromatique, réalisée avec les précautions nécessaires et avec le concours de la digestion par l'hyaluronidase, nous a fourni une image fidèle de la concentration de mucopolysaccharides acides. Ce n'est pas le cas lorsqu'on emploie l'acide périodique-Schiff ou le fer colloïdal qui ne semblent pas être très utiles pour la mise en évidence des substances étudiées.