p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53

10 p.-5 fig.The question of how neural progenitor cells maintain its self-renewal throughout life is a fundamental problem in cell biology with implications in cancer, aging and neurodegenerative diseases. In this work, we have analyzed the p73 function in embryonic neural progenitor cell biology using the neurosphere (NS)-assay and showed that p73-loss has a significant role in the maintenance of neurosphere-forming cells in the embryonic brain. A comparative study of NS from Trp73-/-, p53KO, p53KO;Trp73-/-and their wild-type counterparts demonstrated that p73 deficiency results in two independent, but related, phenotypes: a smaller NS size (related to the proliferation and survival of the neural-progenitors) and a decreased capacity to form NS (self-renewal). The former seems to be the result of p53 compensatory activity, whereas the latter is p53 independent. We also demonstrate that p73 deficiency increases the population of neuronal progenitors ready to differentiate into neurons at the expense of depleting the pool of undifferentiated neurosphere-forming cells. Analysis of the neurogenic niches demonstrated that p73-loss depletes the number of neural-progenitor cells, rendering deficient niches in the adult mice. Altogether, our study identifies TP73 as a positive regulator of self-renewal with a role in the maintenance of the neurogenic capacity. Thus, proposing p73 as an important player in the development of neurodegenerative diseases and a potential therapeutic target.This work was supported by Grants SAF2009- 07897 from Spanish Ministerio de Ciencia e Innovacion (to MCM), Grant from Cajas de Ahorro de Castilla y León (to MCM), and Grants LE030A07 (to MMM) and LE015A10-2 (to MCM) from the Junta de Castilla y León.Peer reviewe

Thermal route for the synthesis of maghemite/hematite core/shell nanowires

Nowadays, iron oxide-based nanostructures are key materials in many technological areas. Their physical and chemical properties can be tailored by tuning the morphology. In particular, the possibility of increasing the specific surface area has turned iron oxide nanowires (NWs) into promising functional materials in many applications. Among the different possible iron oxide NWs that can be fabricated, maghemite/hematite iron oxide core/shell structures have particular importance since they combine the magnetism of the inner maghemite core with the interesting properties of hematite in different technological fields ranging from green energy to biomedical applications. However, the study of these iron oxide structures is normally difficult due to the structural and chemical similarities between both iron oxide polymorphs. In this work, we propose a route for the synthesis of maghemite/hematite NWs based on the thermal oxidation of previously electrodeposited iron NWs. A detailed spectroscopic analysis based on Raman, Mossbauer, and X-ray absorption shows that the ratio of both oxides can be controlled during fabrication. Transmission electron microscopy has been used to check the core/shell structure of the NWs. The biocompatibility and capability of internalization of these NWs have also been proven to show the potential of these NWs in biomedical applications

SOX2+ cell population from normal human brain white matter is able to generate mature oligodendrocytes

expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established..).Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

Background Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. Methods We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. Results We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. Conclusions Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.post-print1360 K