The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation

Neuroblastoma is a highly metastatic tumor that emerges from neural crest cell progenitors. Focal Adhesion Kinase (FAK) is a regulator of cell migration that binds to the receptor Neogenin-1 and is upregulated in neuroblastoma. Here, we show that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin β1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration. Moreover, Neogenin-1, which was detected in all tumor stages and was required for neuroblastoma cell migration, was found in a complex with integrin β1, FAK, and Netrin-1. Importantly, Neogenin-1 promoted neuroblastoma metastases in an immunodeficient mouse model. Taken together, these data show that Neogenin-1 is a metastasis-promoting protein that associates with FAK, activates integrin β1 and promotes neuroblastoma cell migration.This work was supported by the Comisión Nacional de Investigación Científica y Tecnológica [21130521]; Fondo Nacional de Desarrollo Científico y Tecnológico [1140697]; Fondo Nacional de Desarrollo Científico y Tecnológico [1180495]; Red Temática de Investigación Cooperativa en Cancer [RD12/0036/0027]; SAF [SAF2015-65175-R]; Red Temática de Investigación Cooperativa en Cancer [RD12/0036/0027]; PSG: Ministerio de Ciencia, Innovación y Universidades and FEDER funds (RTI2018-093596); JGC: Ministerio de Economía y Competitividad of Spain (PI17CIII/00013), Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (P2017/BMD-3692), Fundación Oncohematología Infantil, AFANION, and Asociación Pablo Ugarte.S

From birth to death: A role for reactive oxygen species in neuronal development

Historically, ROS have been considered toxic molecules, especially when their intracellular concentration reaches high values. However, physiological levels of ROS support crucial cellular processes, acting as second messengers able to regulate intrinsic signaling pathways. Specifically, both the central and peripheral nervous systems are especially susceptible to changes in the redox state, developing either a defense or adaptive response depending on the concentration, source and duration of the pro-oxidative stimuli. In this review, we summarize classical and modern concepts regarding ROS physiology, with an emphasis on the role of the NADPH oxidase (NOX) complex, the main enzymatic and regulated source of ROS in the nervous system. We discuss how ROS and redox state contribute to neurogenesis, polarization and maturation of neurons, providing a context for the spatio-temporal conditions in which ROS modulate neural fate, discriminating between “oxidative distress” and “oxidative eustress”. Finally, we present a brief discussion about the “physiological range of ROS concentration” and suggest that these values depend on several parameters, including cell type, developmental stage, and the source and type of pro-oxidative molecule.Fil: Wilson Rodriguez, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Muñoz Palma, Ernesto. Universidad de Chile; ChileFil: González Billault, Christian. Universidad de Chile; Chile. The Buck Institute for Research on Aging; Estados Unidos. Geroscience Center for Brain Health and Metabolism; Chil

Lithium Complexes Derived of Benzylphosphines: Synthesis, Characterization and Evaluation in the ROP of rac-Lactide and ε-Caprolactone

A series of lithium complexes ([Ph2P(o-C6H4-CH2Li·TMEDA)] (1-Li), [PhP(o-C6H4-CH3)(o-C6H4-CH2Li·TMEDA)] (2-Li), [PhP(o-C6H4-CH2Li·TMEDA)2] (2-Li2) and [P(o-C6H4-CH2Li·TMEDA)3] (3-Li3)) was prepared from mono-, di- and tri-benzylphosphines and varying amounts of nBuLi and was characterized extensively by IR and 1H, 7Li, 13C and 31P NMR spectroscopy. The molecular structures of complexes 1-Li and 2-Li were determined by single-crystal X-ray diffraction studies. The two complexes have monomeric structures in the solid state comprising seesaw lithium atoms. In each case, the ligand exhibits an asymmetric C-C η2-coordination mode and an intramolecular P-Li bond interaction. Theoretical calculations at Density functional theory (DFT) level M06/6111+G(2d,p) show that indeed a P-Li bond is established which can be explained as the P lone pair (sp1.26) being partially delocalized on an available sp2 orbital on Li (sp2.04) and additional bonding contribution of the phosphorous atom to Li stems from further delocalization of a σ P-C orbital into the sp2 orbital on Li. The observed short contact distances between an aromatic ipso carbon and Li in the crystal structures of 1-Li and 2-Li are explained as due to the interaction of a σ C-Li orbital into the π* orbital of a C-C aromatic bond. Preliminary tests show compounds 1-Li, 2-Li, 2-Li2 and 3-Li3 are active catalysts in the solvent free ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) and rac-lactide (rac-LA). High conversions to polycaprolactones were obtained in short periods of time: 1–6 min at 25 °C. Additionally, all four lithium complexes behave as moderately good initiators for the ROP of rac-LA showing high conversions to polylactides at 140 °C in one hour

Novel mechanisms involving redox biology are essential to support axonal growth

Fondap 1515001

A Multicriteria Approach to Integration and Evaluation of Investment Portfolios: The New York Stock Exchange

One of the problems investors often face is deciding on the stocks to include in an investment portfolio. Hence, this article seeks to select investment portfolios considering the 30 leading companies listed on the New York Stock Exchange (NYSE) of the Dow Jones Index. Portfolio selection in this index is carried out by generating a previous ranking of the shares with a novel approach that analyzes their performance using a multiple criteria hierarchical process (MCHP). The current research allows the evaluation of shares and optimizing a portfolio, while developing a procedure that supports a decision-making process for organizations or practitioners to invest in the stock market. The results of analyzing the NYSE generated a portfolio that can be used for interested investors. The main contribution of the application of MCHP and Markowitz model is related to the possibility of replicating the developed procedure to select portfolios in other stock markets

Enfoque multicriterio jerárquico para el análisis de la competitividad de las regiones en México

Competitiveness is related to welfare, economic progress and prosperity and has been an important topic for countries, enterprises, investors and citizens alike. This paper presents a new Multiple Criteria Hierarchy Process (MCHP) for rank the competitiveness of States in Mexico through the analysis of multiple criteria such as legality, economic, social, politic, governmental and environmental, precursors and international relations aspects. An important aspect of the new MCHP proposed is that considers the interaction between criteria and measure the performance of a large number of criteria. The study presents a competitiveness analysis of Mexican regions, regarding the interaction in different level of criteria hierarchy and evaluating the performance of 100 criteria to establish the competitiveness level of States in Mexico. Keywords: Multicriteria, hierarchy approach, competitiveness JEL Codes: C69, C81, D81 Received: 10/07/2020. Accepted: 05/11/2020.  Published: 01/12/2020El objetivo principal de este trabajo es el de evaluar el nivel de competitividad de las regiones de México basado en el desempeño de 10 principales factores provenientes de 100 indicadores. La metodología está basada en el Proceso Jerárquico Multicriterio con la capacidad de analizar el desempeño de un subconjunto de indicadores y el conjunto completo de indicadores, y como impactan en la competitividad de la región. Un aspecto importante de Proceso Jerárquico Multicriterio implementado es que considera la interacción entre criterios (indicadores) y mide el desempeño de un gran número de criterios. La principal contribución de la investigación es la identificación del nivel peor de competitividad de la región, y los factores que requieren más atención por el tomador de decisiones. Palabras clave: Análisis multicriterio, enfoque jerárquico, competitividad. Códigos JEL: C69, C81, D81 Recibido: 10/07/2020. Aceptado: 05/11/2020.  Publicado: 01/12/202

The Netrin-4/Laminin γ1/Neogenin-1 complex mediates migration in SK-N-SH neuroblastoma cells

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. It arises during development of the sympathetic nervous system. Netrin-4 (NTN4), a laminin-related protein, has been proposed as a key factor to target NB metastasis, although there is controversy about its function. Here, we show that NTN4 is broadly expressed in tumor, stroma and blood vessels of NB patient samples. Furthermore, NTN4 was shown to act as a cell adhesion molecule required for the migration induced by Neogenin-1 (NEO1) in SK-N-SH neuroblastoma cells. Therefore, we propose that NTN4, by forming a ternary complex with Laminin γ1 (LMγ1) and NEO1, acts as an essential extracellular matrix component, which induces the migration of SK-N-SH cells