Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas

Copyright © 2011 Cantilena et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel Open Access Publishing Fund.Wnt signalling is an important component of vertebrate development, required for specification of the neural crest. Ten Wnt receptors [Frizzled receptor 1-10 (Fzd1-10)] have been identified so far, some of which are expressed in the developing nervous system and the neural crest. Here we show that expression of one such receptors, Fzd6, predicts poor survival in neuroblastoma patients and marks rare, HIF1/2 α-positive cells in tumour hypoxic areas. Fzd6 positive neuroblastoma cells form neurospheres with high efficiency, are resistant to doxorubicin killing and express high levels of mesenchymal markers such as Twist1 and Notch1. Expression of Fzd6 is required for the expression of genes of the noncanonical Wnt pathway and the spheres forming activity. When transplanted into immunodeficient mice, neuroblastoma cells expressing the Fzd6 marker grow more aggressively than their Fzd6 negative counterparts. We conclude that Fzd6 is a new surface marker of aggressive neuroblastoma cells with stem cell-like features.This work was sponsored by the Wellcome Trust, the RICC cancer fund, SPARKS, the Italian Association for Cancer Research, Regione Liguria and the Italian Ministry of Health

The role of particle mineralogy in mixtures of sands

Several recent studies on mixtures of sands of different granulometries and/or mineralogies have focused on the key factors that might lead the behaviour to change from transitional to not transitional, where a transitional behaviour is characterised by non-convergent compression paths and critical state lines that might be non-unique. The authors present a review of mixtures of different soils showing a complex pattern of compression and shearing behaviour in which transitional behaviour can be caused by relatively small varia- tions to the proportion or nature of soil particles. Laboratory investigations, carried out by means of oedometer tests, have confirmed the role of the mineralogy of the matrix composed by larger grains. This determines the mode of behaviour so that, if there is a strong and stiff matrix made of quartz sand particles, which are either larger than or at least of similar size to the other component, then non-convergent compression paths are likely to occur, no matter whether particle breakage occurs or not

Protein kinase C isoenzymes in human neuroblasts involvement of PKCε in cell differentiation

AbstractAlthough neuronal cells are a major target of phorbol ester action, the activity of the various protein kinase C (PKC) isoenzymes have not been studied in detail in human neuroblasts. Differentiation of the LAN-5 human neuroblastoma cell line by interferon-γ (IFN-γ) is accompanied by a twofold increase in PKC activity. Since PKC is a multigene family, we investigated which isoforms were expressed in control and differentiated cells, and which of these isoenzymes is involved in neuronal differentiation. We found that: (1) PKC activity is higher in differentiated than in undifferentiated cells; (2) RT-PCR analysis showed the expression of mRNA for PKCα, -γ, -δ -ε and-ζ and the absence of mRNA for β in untreated LAN-5 cells; (3) Western blot evaluation with PKC isoform-specific antibodies showed the same pattern of PKC expression in non-differentiated cells; (4) Expression of PKCε mRNA was significantly enhanced by IFN-γ-induced differentiation, while the other isoforms were not affected; (5) Differentiation of LAN-5 cells with IFN-γ or retinoic acid induced overexpression of the PKCε protein, while inhibition of cell proliferation by fetal calf serum starvation was without effect. These findings suggest that expression of PKCε isoform is tightly coupled with neuronal differentiation and may play a role in the maintenance of the differentiated state

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era. Selecting cases, matching clinical benefit. A position paper from the Italian Group of Haematopathology (G.I.E.)

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient

Ultrafast dynamics in unaligned MWCNTs decorated with metal nanoparticles

The relaxation dynamics of unaligned multi-walled carbon nanotubes decorated with metallic nanoparticles have been studied by using transient optical measurements. The fast dynamics due to the short-lived free-charge carriers excited by the pump are not affected by the presence of nanoparticles. Conversely, a second long dynamics, absent in bare carbon nanotubes, appears only in the decorated samples. A combination of experiment and theory allows us to ascribe this long dynamics to relaxation channels involving electronic states localized at the tube-nanoparticle interface

LRRK2 G2019S kinase activity triggers neurotoxic NSF aggregation

Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons within the substantia nigra pars compacta and the presence of protein aggregates in surviving neurons. LRRK2 G2019S mutation is one of the major determinants of familial PD cases and leads to late-onset PD with pleomorphic pathology, including alpha-synuclein accumulation and deposition of protein inclusions. We demonstrated that LRRK2 phosphorylates N-ethylmaleimide sensitive factor (NSF). We observed aggregates containing NSF in basal ganglia specimens from G2019S carrier PD patients and in cellular and animal models expressing the LRRK2 G2019S variant. We found that LRRK2 G2019S kinase activity induces the accumulation of NSF in toxic aggregates. Noteworthy, the induction of autophagy cleared NSF aggregation and rescued motor and cognitive impairment observed in aged hG2019S BAC mice. We suggest that LRRK2 G2019S pathological phosphorylation hampers substrate catabolism, thus causing the formation of cytotoxic protein inclusions