PETROLOGICAL CONSTRAINTS ON THE ORIGIN OF PYROXENITE DYKES IN THE LITHOSPHERIC MANTLE OF THE CHESHMEH-BID OPHIOLITIC MASSIF, SOUTHERN IRAN

The Cheshmeh-Bid ophiolitic massif in the Khajeh-Jamali district (Southern Iran) is dominated by harzburgite-dunite tectonites locally intruded by orthopy-roxenite dikes. These latter are composed of dominant coarse orthopyroxene with minor olivine, Cr-spinel, clinopyroxene and amphibole. Estimated equilibrium temperatures for Mg-hornblende and edenitic amphibole reveal a late stage magmatic origin.The Cheshmeh-Bid orthopyroxenites are characterized by very low Al2O3, CaO, Na2O and TiO2 abundances coupled to relatively high MgO and SiO2contents. They display U-shaped REE patterns, selective LILE enrichment and positive Pb and Sr anomalies. The host harzburgites are highly refractory mantle residues resulting from fluid-assisted melting. Field observations and mineral assemblages suggest that the pyroxenites formed by melt injection along fractures within rather cold ambient harzburgites and chromitites at moderate pressure (P > 1 GPa). Based on bulk-rock compositions and mineral chemistry, we infer that the Cheshmeh-Bid orthopyroxenites originated from the intrusion and crystallization of hydrous Si-rich, low-Ca melts with a boninite signature in a supra-subduction environment. Fine-grained neoblastic domains developed in the pyroxenites in response to subsolidus ductile deformation and recrystallization, which were most likely related to the exhumation of the Cheshmeh-Bid ophiolite massif

Transcriptional activation of the miR-17-92 cluster is involved in the growth-promoting effects of MYB in human Ph-positive leukemia cells.

MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL-expressing cells. We investigated whether MYB silencing modulates microRNA expression in Philadelphia-positive (Ph+) leukemia cells and if MYB-regulated microRNAs are important for the MYB addiction of these cells. Thirty-five microRNAs were modulated by MYB silencing in lymphoid and erythromyeloid chronic myeloid leukemia-blast crisis BV173 and K562 cells; 15 of these were concordantly modulated in both lines. We focused on the miR-17-92 cluster because of its oncogenic role in tumors and found that: i) it is a direct MYB target; ii) it partially rescued the impaired proliferation and enhanced apoptosis of MYB-silenced BV173 cells. Moreover, we identified FRZB, a Wnt/β-catenin pathway inhibitor, as a novel target of the miR-17-92 cluster. High expression of MYB in blast cells from 2 Ph+leukemia patients correlated positively with the miR-17-92 cluster and inversely with FRZB. This expression pattern was also observed in a microarray dataset of 122 Ph+acute lymphoblastic leukemias. In vivo experiments in NOD scid gamma mice injected with BV173 cells confirmed that FRZB functions as a Wnt/β-catenin inhibitor even as they failed to demonstrate that this pathway is important for BV173-dependent leukemogenesis. These studies illustrate the global effects of MYB expression on the microRNAs profile of Ph+cells and supports the concept that the MYB addiction of these cells is, in part, caused by modulation of microRNA-regulated pathways affecting cell proliferation and survival. Copyright© 2019 Ferrata Storti Foundation

Hadronic processes at work in 5BZB J0630-2406

Recent observations are shedding light on the important role that active galactic nuclei (AGN) play in the production of high-energy neutrinos. In this study, we focus on one object, 5BZB J0630-2406, which is among the blazars recently proposed as associated with neutrino emission during the first 7-yr IceCube observations. Modelling the quasi-simultaneous, broad-band spectral energy distribution, we explore various scenarios from purely leptonic to lepto-hadronic models, testing the inclusion of external photon fields. This theoretical study provides a complementary testing ground for the proposed neutrino-blazar association. Despite being historically classified as a BL Lac, our study shows that 5BZB J0630-2406 belongs to the relatively rare sub-class of high-power flat-spectrum radio quasars (FSRQs). Our results indicate that interactions between protons and external radiation fields can produce a neutrino flux that is within the reach of the IceCube detector. Furthermore, the spectral shape of the X-ray emission suggests the imprint of hadronic processes related to very energetic protons.Comment: Accepted for publication. 18 pages, 10 figure

Red blood cells as bioindicators of cardiovascular risk in Kawasaki disease: A case report

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Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week) of 2 -O-methyl-phosphorothioate antisense oligoribonucleotides (AONs) adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres) were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage). In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules

Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week) of 2  -O-methyl-phosphorothioate antisense oligoribonucleotides (AONs) adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres) were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage). In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules

Role of Oxidative Stress in the Cardiovascular Complications of Kawasaki Disease

Kawasaki disease (KD) is a rare and often undiagnosed disease, at least in the western countries. Although its etiology remains unidentified, epidemiological features point to the role of infection and genetic predisposition. KD is characterized by an inflammatory acute febrile vasculitis. Coronary artery involvement is the most important complication of KD and may cause significant coronary stenosis resulting in ischemic heart disease. It has been demonstrated that the major risks in KD progression are the endothelial dysfunction and that systemic oxidative stress together with premature aging of red blood cells and alteration of platelet homeostasis, could play a critical role in the cardiovascular complications associated with KD. This chapter will focus on the role of oxidative stress in endothelial damage and on circulating blood cells of KD patients