Direct Transactivation of the Anti-apoptotic Gene Apolipoprotein J (Clusterin) by B-MYB

B-MYB is a ubiquitously expressed transcription factor involved in the regulation of cell survival, proliferation, and differentiation. In an attempt to isolate B-MYB-regulated genes that may explain the role of B-MYB in cellular processes, representational difference analysis was performed in neuroblastoma cell lines with different levels of B-MYB expression. One of the genes, the mRNA levels of which were enhanced in B-MYB expressing cells, was ApoJ/Clusterin(SGP-2/TRMP-2) (ApoJ/Clusterin), previously implicated in regulation of apoptosis and tumor progression. Here we show that the human ApoJ/Clusterin gene contains a Myb binding site in its 5\' flanking region, which interacts with bacterially synthesized B-MYB protein and mediates B-MYB-dependent transactivation of the ApoJ/Clusterin promoter in transient transfection assays. Endogenous ApoJ/Clusterin expression is induced in mammalian cell lines following transient transfection of a B-MYB cDNA. Blockage of secreted clusterin by a monoclonal antibody results in increased apoptosis of neuroblastoma cells exposed to the chemotherapeutic drug doxorubicin. Thus, activation of ApoJ/Clusterin by B-MYB may be an important step in the regulation of apoptosis in normal and diseased cell

Lack of correlation between N-myc and MAX expression in neuroblastoma tumors and in cell lines: implication for N-myc-MAX complex formation

Detectable levels of MAX messenger RNA were found in a set of human neuroblastoma tumors and established cell lines. MAX mRNA levels were independent of tumor stage and N-myc genomic amplification. By contrast, N-myc mRNA transcripts were detectable only in tumors with amplification of N-myc gene and in cell lines. Analysis by reverse transcriptase polymerase chain reaction and hybridization to specific oligodeoxynucleotide probes revealed approximately equal amounts of two MAX transcripts in all cases analyzed. Immunoprecipitations with a specific antibody to MAX detected two proteins of M(r) 21,000 and 22,000 in approximately equal amounts in all neuroblastoma lines regardless of N-myc amplification and/or expression. On the other hand, protein binding to the myc DNA consensus sequence correlated with N-myc expression in neuroblastoma cells. Thus, N-myc expression might be a limiting factor in the formation of the N-myc-MAX heterodimer in neuroblastomas

A Centralized Win-Win Cooperative Framework for Wi-Fi and 5G Radio Access Networks

Cooperation to access wireless networks is a key approach towards optimising the use of finite radio spectrum resources in overcrowded unlicensed bands and to help satisfy the expectations of wireless users in terms of high data rates and low latency. Although solutions that advocate this approach have been widely proposed in the literature, they still do not consider a number of aspects that can improve the performance of the users’ connections, such as the inclusion of: 1) cooperation among network operators, and 2) users’ quality requirements based on their applications. To fill this gap, in this paper we propose a centralized framework that aims to provide a ‘win-win’ cooperation among Wi-Fi and cellular networks, which takes into account 5G technologies and users’ requirements in terms of Quality of Service (QoS). Moreover, the framework is supported by smart Radio Access Technology (RAT) selection mechanisms that orchestrate the connection of the clients to the networks. In particular, we discuss details on the design of the proposed framework, the motivation behind its implementation, the main novelties, its feasibility and the main components. In order to demonstrate the benefits of our solution, we illustrate efficiency results achieved through the simulation of a smart RAT selection algorithm in a realistic scenario, which mimics the proposed ‘win-win’ cooperation between Wi-Fi and cellular 5G networks and we also discuss potential benefits for wireless and mobile network operators

Validation platform implementation description - D5.2

This deliverable describes different test-beds for the validation of the architecture, algorithms and protocols for the operator governed opportunistic networking as defined in the OneFIT Project. Further on, this deliverable provides a description of the implementation of the OneFIT cognitive management systems CSCI and CMON as well as the C4MS protocol. Also, implementation of the blocks supporting the OneFIT system (JRRM, CCM, DSONPM, and DSM) is described. This document also describes the implementation of the OneFIT scenarios for opportunistic coverage extension, opportunistic capacity extension, infrastructure supported ad-hoc networking and device-to-device communication as well as opportunistic resource aggregation in the backhaul network

Results analysis and validation - D5.3

This deliverable describes the validation processes followed to assess the performance of the algorithms and protocols for the operator governed opportunistic networking as defined in the OneFIT Project. Therefore, this document includes the description of the set-up of the different validation platforms, the design of the test plans for each one of them, and the analysis of the results obtained from the tests. A per-scenario approach rather than a per-platform approach has been followed, so an additional analysis has been performed, gathering the results related to each scenario, in order to validate the premises stated to each one of them. The OneFIT concept has been therefore validated for all foreseen business scenarios

Neuroblastoma: oncogenic mechanisms and therapeutic exploitation of necroptosis

Neuroblastoma (NB) is the most common extracranial childhood tumor classified in five stages (1, 2, 3, 4 and 4S), two of which (3 and 4) identify chemotherapy-resistant, highly aggressive disease. High-risk NB frequently displays MYCN amplification, mutations in ALK and ATRX, and genomic rearrangements in TERT genes. These NB subtypes are also characterized by reduced susceptibility to programmed cell death induced by chemotherapeutic drugs. The latter feature is a major cause of failure in the treatment of advanced NB patients. Thus, proper reactivation of apoptosis or of other types of programmed cell death pathways in response to treatment is relevant for the clinical management of aggressive forms of NB. In this short review, we will discuss the most relevant genomic rearrangements that define high-risk NB and the role that destabilization of p53 and p73 can have in NB aggressiveness. In addition, we will propose a strategy to stabilize p53 and p73 by using specific inhibitors of their ubiquitin-dependent degradation. Finally, we will introduce necroptosis as an alternative strategy to kill NB cells and increase tumor immunogenicity

Chromophore aggregation and photoinduced dichroism in sol-gel films

Photoinduced dichroism (PID) and UV-visible spectroscopic studies have been performed in silica-based thin films prepared by the sol-gel technique, containing Disperse Red 1 (DR1) as trans-cis photoisomerizable chromophore and carbazole as a plasticizer. The absorbances parallel and perpendicular to the induced anisotropy axis, A∥ and A⊥, have been monitored during illumination. Some of the samples show an increase of the average absorbance T0 = (A∥ + 2A⊥)/3 over the initial value. This effect can be interpreted by the presence of aggregates of DR1 molecules, breaking down during illumination and increasing the absorption at the probe wavelength. The formation of the aggregates is evidenced by a blue-shift in the absorption spectra. The carbazole apolar group acts as spacers between the DR1 molecules, effectively avoiding the formation of aggregates. Model equations have been proposed to describe the kinetics of the system and the initial PID data have been fitted by using a simple phenomenological model. © 2007 Elsevier B.V. All rights reserved

Desferrioxamine inhibits induced erythroid differentiation of human leukemic K-562 cells

The iron chelator desferrioxamine reversibly inhibits heme accumulation and globin synthesis in human leukemic K-562 cells induced to express erythroid genes by butyric acid. These results suggest that iron metabolism can modulate globin gene expression. In addition we describe experimental conditions (6.25 μg/ml desferrioxamine) which do not suppress transcription of globin genes and translation of globin mRNA but prevent heme synthesis. Therefore expression of globin genes in butyric acid induced K-562 cells does not require accumulation of heme molecules. Human leukemic K-562 cells cultured with different inducers and treated with desferrioxamine should be used as a useful model system to further analyse the relationship between expression of erythroid genes, iron metabolism and heme accumulation. © 1983