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The study reports that heterozygous germline mutations in the CBL tumor-suppressor gene can result in a phenotype with clinical features fitting or partly overlapping Noonan syndrome (NS). Evidence suggests germline mutations in CBL alter development to cause a clinically variable condition resembling NS, with possible predisposition to malignancies.

Objective: The aim of this study was to identify whether the rapid membrane-associated pathway of the glucocorticoid receptor (GR) is active in erythroid cells and plays any role in determining the reversible inhibition on erythroid maturation exerted by GR. Materials and Methods: First we determined the biological effects (inhibition of apoptosis and induction of β-globin expression) induced in primary erythroblasts by erythropoietin (EPO) and the GR agonist dexamethasone (DXM), alone and in combination. Next, by biochemical analysis, we determined the association between GR and EPO receptor in proerythroblasts generated in vitro from 10 normal adult donors. These studies also analyzed the levels of signal transducers and activators of transcription−5 (STAT-5) phosphorylation induced when the cells were stimulated with DXM alone or in combination with EPO. Results: DXM antagonized the β-globin messenger RNA increases, but not the inhibition of apoptosis induced by EPO in primary cells. DXM also antagonized the ability of EPO to induce STAT-5 phosphorylation in these cells. In fact, EPO and DXM alone, but not in combination, induced phosphorylation and nuclear translocation of STAT-5. The inhibition likely occurred through an interaction between the two receptors because GR became associated with the EPO receptor and STAT-5 in cells stimulated with EPO and DXM. Conclusion: These data suggest that glucocorticoids inhibit erythroid maturation not only through a transcriptional mechanism, but also through a rapid membrane-associated pathway that interferes with EPO receptor signaling. [Copyright &y& Elsevier]

Macrophage cell lines exhibit different responses to IFN-γ depending on their maturation stage. We investigated the mechanisms underlying the differential IFN-γ responsiveness in the less mature P388.D1 and in mature RAW264.7 cells. A reduction in the binding activity of the signal transducer and activator of transcription-1 (STAT-1) to different STAT binding elements (SBEs) was observed in P388.D1. This reduced binding activity was not due to an impaired STAT-1 activation. Studies on the expression of a negative regulator of cytokine signalling, protein-inhibiting activated STAT-1 (PIAS-1), showed that this protein was expressed constitutively at high levels in P388.D1. Forced expression of a PIAS-1 homologue, the Gu binding protein (GBP), inhibited the STAT-1-mediated gene activation in RAW264.7 cells, whereas a construct expressing the 5′ portion of GBP in the antisense orientation reverts the IFN-γ-resistant phenotype of P388.D1. Thus, our results indicate that PIAS-1 may account for the differential IFN-γ responsiveness in macrophage cell lines at different stages of maturation. [Copyright &y& Elsevier]

• An Electrogenic and hydrocarbonoclastic biofilm as response to oil spill • Biofilm microbes are involved in electrogenic and hydrocarbonoclastic activity • Biofilm was connected to bacterial filaments to transfer electrons at distance • Electrogenic filamentation was associated to "myelin like" expression pattern • A vertical and spontaneous Liquid Microbial Fuel Cell (L-MFC) was created The oil-water interface formed during an oil spill represents a challenging environment for pelagic communities living in aquatic ecosystems. At this anoxic barrier, we report the formation of a microbial hydrocarbonoclastic biofilm capable of electron transfer along the water column. This biofilm generated a membrane of surface-active compounds that allowed the spontaneous separation of electrical charges, causing the establishment of an anodic and a cathodic region and, as a result, the spontaneous creation of a liquid microbial fuel cell. Such floating biofilm was connected to the water column underneath by floating filaments that could contribute to oxygen reduction at distance. The filaments revealed an unusual lipid content induced by anoxic conditions, with prominent ultrastructural features similar to myelin found in oligodendrocytes of the vertebrate nervous system. Furthermore, these filaments showed an interesting cross-reactivity towards different epitopes of the myelin basic protein (MBP) and Claudin 11 (O 4) of human oligodendrocytes. The presence of a network of filaments similar to myelin suggests the probable existence of evolutionary connections between very distant organisms. Collectively these results suggest a possible mechanism for how lake microbial communities can adapt to oil spills while offering an interesting starting point for technological developments of liquid microbial fuel cells related to the study of hydrocarbon-water interfaces. The data that support the findings of this study are openly available in figshare at https://figshare.com/s/72bc73ae14011dc7920d. [Display omitted] [ABSTRACT FROM AUTHOR]