Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis

Neuroblastoma is a pediatric cancer that can present as low- or high-risk tumors (LR-NBs and HR-NBs), the latter group showing poor prognosis due to metastasis and strong resistance to current therapy. Whether LR-NBs and HR-NBs differ in the way they exploit the transcriptional program underlying their neural crest, sympatho-adrenal origin remains unclear. Here, we identified the transcriptional signature distinguishing LR-NBs from HR-NBs, which consists mainly of genes that belong to the core sympatho-adrenal developmental program and are associated with favorable patient prognosis and with diminished disease progression. Gain- and loss-of-function experiments revealed that the top candidate gene of this signature, Neurexophilin-1 (NXPH1), has a dual impact on NB cell behavior in vivo: whereas NXPH1 and its receptor α-NRXN1 promote NB tumor growth by stimulating cell proliferation, they conversely inhibit organotropic colonization and metastasis. As suggested by RNA-seq analyses, these effects might result from the ability of NXPH1/α-NRXN signalling to restrain the conversion of NB cells from an adrenergic state to a mesenchymal one. Our findings thus uncover a transcriptional module of the sympatho-adrenal program that opposes neuroblastoma malignancy by impeding metastasis, and pinpoint NXPH1/α-NRXN signaling as a promising target to treat HR-NBs.This work was supported by grants from the Ministerio de Ciencia e Innovacion, Gobierno de España (MCINN; BFU2016-81887-REDT and BFU2016-77498-P) and the Asociación Española Contra el Cancer (AECC CI_2016) to EM, from the Fondo de Investigación en Salud (FIS) - Instituto de salud Carlos III (PI14/00038) and the NEN association (Association of Families and Friends of Patients with Neuroblastoma) to CL, from the Instituto de Salud Carlos III-FSE (MS17/00037; PI18/00014; PI21/00020) to TC-T, from Instituto de Salud Carlos III (CP22/00127, co-funded by European Social Fund “Investing in your future”) to BMJ, from the Agence Nationale pour la Recherche (ANR-17-CE14-0023-01, ANR-17-CE14-0009-02) and the city of Paris (Emergence program) to ELG, from ISCIII-FEDER (CP13/00189 and CPII18/00009) to AMC. LF received a PhD fellowship from the Spanish Ministry of Science, Education and Universities (FPU AP2012-2222). LT-D was funded by a FPI Fellowship (PRE2019-088005). GLD was supported by the Asociación Española Contra el Cancer (AECC #AIO14142105LED)

Interaction of bentonite with supercritically carbonated concrete

Bentonite and concrete are essential components in construction of a geological high level nuclear waste (HLNW) repository. Conventional Ordinary Portland Cement (OPC) used for concretes gives a pore water leachate with a pH as high as 13.5 in contact with ground water. This alkaline plume of leaching waters might perturb the engineered barrier system, which might include bentonite buffer, backfill material or the near-field host rock. The accepted solution to maintain the bentonite stability, which is controlled by the pH, is to develop cementitious materials with pore water pH around 11. Four lixiviation experiments representative of long-term interaction of solids and pore fluids at the concrete/bentonite interface were performed with two types of cement paste, Portland and calcium aluminate cement, before and after being carbonated under supercritical conditions, with granite water at 80 °C. The evolution of the pH indicates that the supercritical carbonation reduced the alkalinity of the cement pastes and calcite likely controls the equilibrium of Ca at the end of the experiments. The bentonite helps to buffer the alkalinity of concrete leachates through several reactions such as dissolution of montmorillonite and precipitation of secondary products as trioctahedral smectite, zeolites (gismondine), and presumably Mg hydroxides and amorphous gels. Carbonation may reduce propagation of the alkaline plume and enhance the barrier performance.Peer reviewe

Complex Formation via Hydrogen bonding between Rhodamine B and Montmorillonite in Aqueous Solution

Abstract This study investigates the adsorption mechanism differences among four nitrogenous dyes, sulforhodamine G (SRG), uncharged/deprotonated rhodamine B (RhB), orange II (Or II) and methyl blue (MB) by montmorillonite (MMT). MMT adsorption capacity for cationic MB was three times that of uncharged RhB and anionic SRG, while anionic Or II was not absorbed. Colloidal MMT particles have two types of surfaces, basal and edge, that interact with nitrogenous dyes very differently. The surface acidity of MMT was characterized with the pyridine adsorption method using in-situ diffuse reflectance infrared Fourier transform spectroscopy (in-situ DRIFTS). Adsorption of cationic MB was compared with the adsorption of RhB. In-situ attenuated total reflectance Fourier transform infrared (in-situ ATR-FTIR) spectroscopy indicated that a nitrogen atom on RhB complexes with a metal hydroxyl on an MMT edge through a water bridge. The highly polar edge hydroxyl is important to hydrogen bond formation. Cation ion exchange and washing experiments, as well as studies on the effect of temperature, pH and ionic strength on adsorption further clarified the adsorption mechanism. Our results provide insights into the effects of molecular structure on the adsorption of nitrogenous dyes by clay and the role of edge surfaces in the adsorption process

Smectites and zeolites in ash from the 2010 summit eruption of Eyjafjallajökull volcano, Iceland

Hydrothermal alteration minerals are often incorporated in volcanic ash from phreatic and phreatomagmatic activity. Here we assess the presence and abundance of such minerals in the ash materials produced during the April- May 2010 initial phreatomagmatic (phase I) and subsequent magmatic (phases II and III) eruptions of Eyjafjallajökull volcano, Iceland. The results of X-ray diffraction analyses reveal significant quantities of smectites (up to 4 wt%, mainly as saponite) and zeolites (up to 7 wt%) in ash from phase I. While a minor amount of smectites (<0.5 wt%) is present in ash from the subsequent weak explosive activity (phase II), both smectites and zeolites are absent in phase III ash. This material was generated following abrupt rejuvenation of explosive activity in the absence of magma-ice/water interaction. Smectites and zeolites in phase I ash result primarily from scouring of altered volcanic rocks in the subsurface, although some may derive also from water-rock interaction within the summit ice cauldrons through which fragmented magma was injected.We show that incorporation of smectites and zeolites in phase I ash can explain its anomalously high specific surface area. Further, the presence of these minerals in ash may enhance its ability to act as ice nuclei as well as favour particle aggregation processes in the volcanic plume/cloud. Finally, the Eyjafjallajökull eruption represents another case in which ash fallout acted as an exogenic source of 2:1-type clay minerals in volcanic soils