Rendimientos productivos de terneros cebones de razas asturianas bajo dos estrategias de manejo

publishedTomo I . Sección: Sistemas Ganaderos-Economía y Gestión. Sesión: Vacuno carne II. Ponencia nº

Maintenance of Undifferentiated State and Self-Renewal of Embryonic Neural Stem Cells by Polycomb Protein Ring1B

12 pages, 7 figures.-- PMID: 19544461 [PubMed].-- Printed version published Jul 2009.Supporting information (Suppl. figures S1-S9, tables S1-S2) available at: http://www3.interscience.wiley.com/journal/122302104/suppinfoCell lineages generated during development and tissue maintenance are derived from self-renewing stem cells by differentiation of their committed progeny. Recent studies suggest that epigenetic mechanisms, and in particular the Polycomb group (PcG) of genes, play important roles in controlling stem cell self-renewal. Here, we address PcG regulation of stem cell self-renewal and differentiation through inactivation of Ring1B, a histone H2A E3 monoubiquitin ligase, in embryonic neural stem cells (NSCs) from the olfactory bulb of a conditional mouse mutant line. We show that neural stem/progenitor cell proliferation in vivo and in neurosphere assays is impaired, lacking Ring1B, and their self-renewal and multipotential abilities, assessed as sphere formation and differentiation from single cells, are severely affected. We also observed unscheduled neuronal, but not glial, differentiation of mutant stem/progenitor cells under proliferating conditions, an alteration enhanced in cells also lacking Ring1A, the Ring1B paralog, some of which turned into morphologically identifiable neurons. mRNA analysis of mutant cells showed upregulation of some neuronal differentiation-related transcription factors and the cell proliferation inhibitor Cdkn1a/p21, as well as downregulation of effectors of the Notch signaling pathway, a known inhibitor of neuronal differentiation of stem/progenitor cells. In addition, differentiation studies of Ring1B-deficient progenitors showed decreased oligodendrocyte formation in vitro and enhanced neurogenesis and reduced gliogenesis in vivo. These data suggest a role for Ring1B in maintenance of the undifferentiated state of embryonic neural stem/progenitor cells. They also suggest that Ring1B may modulate the differentiation potential of NSCs to neurons and glia.M.R-T. and H. M-G. were recipients of FPU and FPI fellowships, from the Ministerio de Educacion y Ciencia and Comunidad de Madrid, respectively. This work was supported by grants SAF2007-65957-C02-01 (M.V.), the Onco-Cycle program from the Comunidad de Madrid (M.V.), SAF2004-05798, and CIBERNED CB06/05/0065 from Instituto de Salud Carlos III (C.V-A.).Peer reviewe

Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia.

The malignant microenvironment plays a major role in the development of resistance to therapies and the occurrence of relapses in acute myeloid leukemia (AML). We previously showed that interactions of AML blasts with bone marrow macrophages (MΦ) shift their polarization towards a protumoral (M2-like) phenotype, promoting drug resistance; we demonstrated that inhibiting the colony-stimulating factor-1 receptor (CSF1R) repolarizes MΦ towards an antitumoral (M1-like) phenotype and that other factors may be involved. We investigated here macrophage migration inhibitory factor (MIF) as a target in AML blast survival and protumoral interactions with MΦ. We show that pharmacologically inhibiting MIF secreted by AML blasts results in their apoptosis. However, this effect is abrogated when blasts are co-cultured in close contact with M2-like MΦ. We next demonstrate that pharmacological inhibition of MIF secreted by MΦ, in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF), efficiently reprograms MΦ to an M1-like phenotype that triggers apoptosis of interacting blasts. Furthermore, contact with reprogrammed MΦ relieves blast resistance to venetoclax and midostaurin acquired in contact with CD163 <sup>+</sup> protumoral MΦ. Using intravital imaging in mice, we also show that treatment with MIF inhibitor 4-IPP and GM-CSF profoundly affects the tumor microenvironment in vivo: it strikingly inhibits tumor vasculature, reduces protumoral MΦ, and slows down leukemia progression. Thus, our data demonstrate that MIF plays a crucial role in AML MΦ M2-like protumoral phenotype that can be reversed by inhibiting its activity and suggest the therapeutic targeting of MIF as an avenue towards improved AML treatment outcomes

Effects of challenge dose and inoculation route of virulent Neospora caninum Nc-Spain7 isolate in pregnant cattle at mid gestation

Trabajo presentado al: 4th International Meeting on Apicomplexa in Farm Animals. (11-14 October 2017 - Madrid, Spain).Peer Reviewe