Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells

Tumor-initiating cells constitute a population within a tumor mass that shares properties with normal stem cells and is considered responsible for therapy failure in many cancers. We have previously demonstrated that knockdown of the nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits retinoic acid-mediated differentiation and results in a more aggressive phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in the nuclear envelope composition occur during tumor progression. Based on our previous data and considering that Lamin A/C is expressed in differentiated tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward a stem-like phenotype, thus influencing the development of tumor-initiating cells in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers the development of a tumor-initiating cell population with self-renewing features in human neuroblastoma cells. We also demonstrates that the development of TICs is due to an increased expression of MYCN gene and that in neuroblastoma exists an inverse relationship between LMNA and MYCN expression

Seismic noise cross-correlation in the urban area of Benevento city (Southern Italy)

This article has been accepted for publication in Geophysical Journal International ©: The Authors 2019. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved. Uploaded in accordance with the publisher's self-archiving policy.In the last decade the use of passive methods has become appealing in reconstructing the properties of the propagation medium by seismic ambient noise data, without the use of localized natural or artificial sources. A temporary seismic network was installed in the urban area of Benevento (southern Italy) in order to characterize the shallow structure of the city using stable methods for the analysis of the seismic noise continuously acquired by stations. The city of Benevento is one of the italian areas with highest seismic hazard, and at present the region is affected by low energy swarms and sparse events (Ml ≤ 4.1). It has been struck by several destructive historical earthquakes, the strongest of which occurred in 1456, 1688, 1805 with associated MCS intensity up to X–XI. We used the sixteen seismic stations installed in Benevento to record ambient noise for about 1 month. The stations were equipped with different seismic instruments: (i) digitizers Quanterra Q330 connected to Le3d-5 s short-period sensors; (ii) Nanometrics Centaur digitizers coupled with Trillium Compact 120s broad-band velocimeters; (iii) one station with Episensor force balance accelerometer connected to a D6BB-DIN Staneo digitizer. Interstations Green's functions were reconstructed by the cross-correlation of continuous ambient noise data, and surface waves signals were extracted from Green's Functions (GFs) for investigating the elastic properties of the subsurface structure. In this regard, we performed the beamforming analysis to test the hypothesis of isotropy distribution of noise sources on which the cross-correlation method is based, and the particle motion analysis to confirm the presence of surface Rayleigh waves in the GFs. We analysed the temporal stability of the cross-correlated signals and the results show that 2 weeks of continuous measurements are sufficient to stabilize the surface waves signal extracted from the GFs. The phase velocity dispersion curves are computed for 115 station pairs through the use of a far-field representation of the surface-wave GFs and an image transformation technique. Our strategy based on cross-correlation analysis provides robust phase-velocity dispersion curves that vary approximately from 1.4 km s–1 at 0.7 Hz to 0.6 km s–1 at 5 Hz. Different pairs were selected for the inversion of phase-velocity dispersion curves aimed to derive 1-D shear-wave velocity (Vs) profiles (up to a maximum depth of about 500 m) representative of some areas of the city characterized by different soil deposits.Published1524–15425T. Sismologia, geofisica e geologia per l'ingegneria sismicaJCR Journa

Ground Response and Historical Buildings in Avellino (Campania, Southern Italy): Clues from a Retrospective View Concerning the 1980 Irpinia-Basilicata Earthquake

Cultural heritage represents our legacy with the past and our identity. However, to assure heritage can be passed on to future generations, it is required to put into the field knowledge as well as preventive and safeguard actions, especially for heritage located in seismic hazard-prone areas. With this in mind, the article deals with the analysis of ground response in the Avellino town (Campania, Southern Italy) and its correlation with the effects caused by the 23rd November 1980 Irpinia earthquake on the historical buildings. The aim is to get some clues about the earthquake damage cause-effect relationship. To estimate the ground motion response for Avellino, where strong-motion recordings are not available, we made use of the seismic hazard disaggregation. Then, we made extensive use of borehole data to build the lithological model so being able to assess the seismic ground response. Overall, results indicate that the complex subsoil layers influence the ground motion, particularly in the lowest period (0.1–0.5 s). The comparison with the observed damage of the selected historical buildings and the maximum acceleration expected indicates that the damage distribution cannot be explained by the surface geology effects alone

Ambient noise HVSR measurements in the Avellino historical centre and surrounding area (southern Italy). Correlation with surface geology and damage caused by the 1980 Irpinia-Basilicata earthquake

The article deals with the results of extensive surveys conducted in the town of Avellino, in southern Italy, with the aim of studying the site seismic response. Avellino is a town located in the Apennine Chain in Irpinia, which is a region characterized by a high seismic hazard. Several strong earthquakes hit the town in the past, the last of which occurred on 23 November 1980 (Mw = 6.8). In the last decades since that event, background low magnitude seismicity persists, including few moderate earthquakes. In order to analyse the site seismic response, our data set was made up by borehole and downhole records, ambient noise measurements both in free-field and inside buildings, and macroseismic data related to the 1980 Irpinia-Basilicata earthquake. With the intention of ascertaining the occurrence of resonance effects influencing the distribution of the earthquake damage, we performed a correlated analysis of all the data acquired. HVSR free-field peak frequencies, joined with the data obtained from previous surveys [22], agree with the computed 1D resonance frequencies and are in the range between 1.6 and 13.0 Hz. The resonance frequencies for fifteen typical buildings in Avellino, which were partly estimated from ambient noise measurements and partly by applying the Italian regulation code, are in the range between 1.2 and 4.6 Hz, so showing that soil-structure resonance effects can be generated in a wide area of the town. Finally, we drew up a detailed damage map, related to the 1980 earthquake, which affected Avellino seriously. From our research two aspects come to light. The first regards the fact that soil-structure resonance effects can be generated in the town and were possibly associated to some buildings damaged by the 1980 earthquake. The second concerns the circumstance that the amplitudes of HVSR peaks correlate well with the rock/soil velocity contrast at depth, but do not show a relationship with the earthquake damage pattern. The results of this study will be useful in view of putting into the field suitable risk mitigation countermeasures.University Fund for Research – Ministry of Education, University and Research, MIUR-FRA, 2015–2016Published211-2225T. Sismologia, geofisica e geologia per l'ingegneria sismicaJCR Journa

Topographic effects observed at Amatrice hill during the 2016–2017 Central Italy seismic sequence

The estimate of seismic site effects by experimental approaches is based on different assumptions aimed at simplifying the complex actual site conditions and related uncertainties. However, the reliability of the results can increase if the experimental data is focused on quite strong seismic sequences and the on-site acquisition of a large number of signals is deemed strategic for the assessment of the expected phenomena. Based on these considerations, the ground motion at the Red Zone sector of Amatrice hill, violently struck by the 2016–2017 Central Italy seismic sequence, was analyzed via an observational approach. A large set of weak motions (moment magnitude Mw 2.5–3.9) was analyzed in this study by means of standard (SSR) and horizontal to vertical (HVSR) spectral ratio techniques. The results from the experimental analysis of the site effects by using weak motion and noise signals show a significant amplification at the top of Amatrice hill with a remarkable polarization of the motion and changes in spectral shapes according to the topographic setting of the relief

Clinical and molecular study in a long-surviving patient with MLASA syndrome due to novel PUS1 mutations

Myopathy-lactic acidosis-sideroblastic anemia (MLASA) syndrome is a rare autosomal recessive disease. We studied a 43-year-old female presenting since childhood with mild cognitive impairment and sideroblastic anemia. She later developed hepatopathy, cardiomyopathy, and insulin-dependent diabetes. Muscle weakness appeared in adolescence and, at age 43, she was unable to walk. Two novel different mutations in the PUS1 gene were identified: c.487delA (p.I163Lfs*4) and c.884 G>A (p.R295Q). Quantitative analysis of DNA from skeletal muscle biopsies showed a significant increase in mitochondrial DNA (mtDNA) content in the patient compared to controls. Clinical and molecular findings of this patient widen the genotype-phenotype spectrum in MLASA syndrome

Seismic site effects in the Red Zone of Amatrice hill detected via the mutual sustainment of experimental and computational approaches

This paper presents the results of numerical analyses of ground motion in the Red Zone sector of Amatrice hill, violently struck by the 2016–2017 Central Italy seismic sequence. The methodologies used in processing the data to define the numerical model are firstly described. The results obtained from the computational analyses are then presented and discussed by comparing them with experimental data set of weak motion recordings. Computational analyses were performed via both a 2D-numerical FEM model and a pseudo-three-dimensional hybrid model (SiSeRHMap) which develops multispectral maps taking into account topographic effects. Starting from available geological data and geophysical measurements, an original and specific subsoil GIS model was developed and utilised to perform the computational analyses. The preliminary map for fundamental periods computed from the subsoil model is in good agreement with the experimental data. A restricted set of weak ground motions acquired from an accelerometric station located in a reference site was used as input for the numerical analyses, while the signals of the corresponding events recorded at the top of the hill were used as targets in the reliability evaluation analysis of the outputs. In the area of Amatrice hill, which is characterized by a complex geological and topographical context, the reliability analysis shows a good performance of the hybrid model compared to the 2D-FEM model in the prediction of seismic response. Agreement generally was also good with regards to the experimental and computational results, both in relation to the amplitude and to the shape of the spectral amplification that change depending on the hill sector. Considering the predictive reliability of the models, a high amplification, due to topographic effects, was observed for the Red Zone by performing a back-simulation of the 24th August 2016 main shock. The analysis results highlight also that the maximum amplification factors, based on the definition of the Housner intensity, occur in the interval of periods 0–0.5 s covering the fundamental period range of the buildings in this area

SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder

Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology