MicroRNA‐34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis

Aims: Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signalling pathway. Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers in the brain. We previously reported microRNA-34a (miR-34a) among the most upregulated miRs in tubers. Here, we characterised miR-34a expression in tubers with the focus on the early brain development and assessed the regulation of mTORC1 pathway and corticogenesis by miR-34a. Methods: We analysed the expression of miR-34a in resected cortical tubers (n = 37) compared with autopsy-derived control tissue (n = 27). The effect of miR-34a overexpression on corticogenesis was assessed in mice at E18. The regulation of the mTORC1 pathway and the expression of the bioinformatically predicted target genes were assessed in primary astrocyte cultures from three patients with TSC and in SH-SY5Y cells following miR-34a transfection. Results: The peak of miR-34a overexpression in tubers was observed during infancy, concomitant with the presence of pathological markers, particularly in giant cells and dysmorphic neurons. miR-34a was also strongly expressed in foetal TSC cortex. Overexpression of miR-34a in mouse embryos decreased the percentage of cells migrated to the cortical plate. The transfection of miR-34a mimic in TSC astrocytes negatively regulated mTORC1 and decreased the expression of the target genes RAS related (RRAS) and NOTCH1. Conclusions: MicroRNA-34a is most highly overexpressed in tubers during foetal and early postnatal brain development. miR-34a can negatively regulate mTORC1; however, it may also contribute to abnormal corticogenesis in TSC

Carbon nanotubes

Carbon nanotubes (CNTs) are remarkable objects that once looked set to revolutionize the technological landscape in the near future. Since the 1990s and for twenty years thereafter, it was repeatedly claimed that tomorrow’s society would be shaped by nanotube applications, just as silicon-based technologies dominate society today. Space elevators tethered by the strongest of cables, hydrogen-powered vehicles, artificial muscles: these were just a few of the technological marvels that we were told would be made possible by the science of carbon nanotubes. Of course, this prediction is still some way from becoming reality; most often the possibilities and potential have been evaluated, but actual technological development is facing the unforgiving rule that drives the transfer of a new material or a new device to market: profitability. New materials, even more so for nanomaterials, no matter how wonderful they are, have to be cheap to produce, constant in quality, easy to handle, and nontoxic. Those are the conditions for an industry to accept a change in its production lines to make them nanocompatible. Consider the example of fullerenes – molecules closely related to nanotubes. The anticipation that surrounded these molecules, first reported in 1985, resulted in the bestowment of a Nobel Prize for their discovery in 1996. However, two decades later, very few fullerene applications have reached the market, suggesting that similarly enthusiastic predictions about nanotubes should be approached with caution, and so should it be with graphene, another member of the carbon nanoform family which joined the game in 2004, again acknowledged by a Nobel Prize in 2010. There is no denying, however, that the expectations surrounding carbon nanotubes are still high, because of specificities that make them special compared to fullerenes and graphene: their easiness of production, their dual molecule/nano-object nature, their unique aspect ratio, their robustness, the ability of their electronic structure to be given a gap, and their wide typology etc. Therefore, carbon nanotubes may provide the building blocks for further technological progress, enhancing our standard of living. In this chapter, we first describe the structures, syntheses, growth mechanisms, and properties of carbon nanotubes. Then we introduce nanotube-based materials, which comprise on the one hand those formed by reactions and associations of all carbon nanotubes with foreign atoms, molecules and compounds, and on the other hand, composites, obtained by incorporating carbon nanotubes in various matrices. Finally, we will provide a list of applications currently on the market, while skipping the potentially endless and speculative list of possible applications

Carbon nanotubes

International audienceCarbon nanotubes (CNT s) are remarkable objects that once looked set to revolutionize the technological landscape in the near future. Since the 1990s and for twenty years thereafter, it was repeatedly claimed that tomorrow's society would be shaped by nanotube applications, just as silicon-based technologies dominate society today. Space elevators tethered by the strongest of cables, hydrogen-powered vehicles, artificial muscles: these were just a few of the technological marvels that we were told would be made possible by the science of carbon nanotubes. Of course, this prediction is still some way from becoming reality; most often the possibilities and potential have been evaluated, but actual technological development is facing the unforgiving rule that drives the transfer of a new material or a new device to market: profitability. New materials, even more so for nanomaterials, no matter how wonderful they are, have to be cheap to produce, constant in quality, easy to handle, and nontoxic. Those are the conditions for an industry to accept a change in its production lines to make them nanocompatible. Consider the example of fullerenes – molecules closely related to nanotubes. The anticipation that surrounded these molecules, first reported in 1985, resulted in the bestowment of a Nobel Prize for their discovery in 1996. However, two decades later, very few fullerene applications have reached the market, suggesting that similarly enthusiastic predictions about nanotubes should be approached with caution, and so should it be with graphene, another member of the carbon nanoform family which joined the game in 2004, again acknowledged by a Nobel Prize in 2010. There is no denying, however, that the expectations surrounding carbon nanotubes are still high, because of specificities that make them special compared to fullerenes and graphene: their easiness of production, their dual molecule/nano-object nature, their unique aspect ratio, their robustness, the ability of their electronic structure to be given a gap, and their wide typology etc. Therefore, carbon nanotubes may provide the building blocks for further technological progress, enhancing our standard of living. In this chapter, we first describe the structures, syntheses, growth mechanisms, and properties of carbon nanotubes. Then we introduce nanotube-based materials, which comprise on the one hand those formed by reactions and associations of all-carbon nanotubes with foreign atoms, molecules and compounds, and on the other hand, composites, obtained by incorporating carbon nanotubes in various matrices. Finally, we will provide a list of applications currently on the market, while skipping the potentially endless and speculative list of possible applications