Seismic images of an extensional basin, generated at the hangingwall of a low-angle normal fault: the case of the Sansepolcro basin (Central Italy)

The study of syntectonic basins, generated at the hanging-wall of regional low-angle detachments, can help to gain a better knowledge of these important and mechanically controversial extensional structures, constraining their kinematics and timing of activity. Seismic reflection images constrain the geometry and internal structure of the Sansepolcro Basin (the northernmost portion of the High Tiber Valley). This basin was generated at the hangingwall of the Altotiberina Fault (AtF), an E-dipping low-angle normal fault, active at least since Late Pliocene, affecting the upper crust of this portion of the Northern Apennines. The dataset analysed consists of 5 seismic reflection lines acquired in the 80s’ by ENI-Agip for oil exploration and a portion of the NVR deep CROP03 profile. The interpretation of the seismic profiles provides a 3-D reconstruction of the basin’s shape and of the sedimentary succession infilling the basin. This consisting of up to 1200 m of fluvial and lacustrine sediments: this succession is much thicker and possibly older than previously hypothesised. The seismic data also image the geometry at depth of the faults driving the basin onset and evolution. The western flank is bordered by a set of E-dipping normal faults, producing the uplifting and tilting of Early to Middle Pleistocene succession along the Anghiari ridge. Along the eastern flank, the sediments are markedly dragged along the SW-dipping Sansepolcro fault. Both NE- and SW-dipping faults splay out from the NE-dipping, low-angle Altotiberina fault. Both AtF and its high-angle splays are still active, as suggested by combined geological and geomorphological evidences: the historical seismicity of the area can be reasonably associated to these faults, however the available data do not constrain a unambiguous association between the single structural elements and the major earthquakes

Seismic reflection data in the Umbria Marche Region: limits and capabilities to unravel the subsurface structure in a seismically active area

Before seismic data were made available, the subsurface setting of the Umbria-Marche area was mainly derived from the extrapolation of surface data and from models resulting from analogies with other mountain chains around the world. During the ‘90s industrial seismic data availability considerably increased, allowing the definition of new, previously unknown features. Beside the industrial seismic data availability, a deep crustal, near vertical seismic section trending E-W was acquired (CROP-03) across the Italian peninsula from the Tyrrhenian to the Adriatic coast. The subsurface data defined the compressional deformation style (thin- Vs thick- skinned) and the extensional deformation style. A set of east-dipping low-angle-normal faults, which dissect the previous compressional structures and which are the dominant features controlling the extension of the Apennines were recognised. The subsequent application of the seismic data interpretation to seismotectonic issues, defined in more detail the subsurface geometries of the active faults and the relationships between upper crust structure and seismicity

SEISMIC ANISOTROPY AND MICRO-SEISMICITY IN THE UPPER CRUST AT NORTH OF GUBBIO BASIN (CENTRAL ITALY): RELATION WITH THE SUBSURFACE GEOLOGICAL STRUCTURES AND THE ACTIVE STRESS FIELD

During the months of April and May 2010, a seismic sequence (here named “Pietralunga seismic sequence”) took place in the northeastern part of the Gubbio basin (Northern Apennines); this area is well known to be interested by a continuous background micro-seismic activity. The sequence was recorded both by the INGV National Seismic Network, and by the stations installed by the Project “AIRPLANE” (financially supported by MIUR-Italian Ministry of Education and Research) with the aim of investigating the seismogenetic processes in the Alto Tiberina Fault (ATF) system region. In this work we present the anisotropic results at four stations: ATFO, ATPC, ATPI, ATVO located around the northern termination of the Gubbio basin that well delimit both the seismic se- quence and the whole 2010 seismicity (about 2500 events). The study of seismic anisotropy has provided useful information for the interpretation and evaluation of the stress field and active crustal deformation. Seismic anisotropy can yield valuable information on upper crustal structure, fracture field, and presence of fluid-saturated rocks. Moreover, the large number of seismic waveforms recorded especially during the Pietralunga sequence allows us also to study the spatio-temporal changes of anisotropic parameters to better understand its evolution and the possible correlation to the presence and migration of fluids

To be or not to be a germ cell: The extragonadal germ cell tumor paradigm

In the human embryo, the genetic program that orchestrates germ cell specification in-volves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neo-plasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types

The MOLE Drilling Project: Laboratory at Depth on an Active Fault in Central Italy

Several fundamental questions concerning: i) the geophysical and geochemical processes controlling normal faulting and earthquake ruptures during moderate-to-large seismic events and ii) the low angle normal fault paradox, still need to be fully answered. In this work we aim to present an example of low angle normal fault (Alto Tiberina Fault) located in the Northern Apennines (Italy) showing conclusive evidence of its seismic activity. This fault is a likely target of an international project: the MOLE (Multidisciplinary Observatory and Laboratory of Experiments) Drilling project. Indeed, under the auspices of the International Continental Scientific Drilling Program a workshop is being organized in Italy next spring 2008, to promote the creation of an international multidisciplinary team of scientists, to discuss the project in detail and also to prepare a full proposal for ICDP. This project wants to investigate the inner structure of normal faults in Central Italy to get physical constraints on the processes controlling faulting and earthquake mechanics. The Umbria-Marche sector of Northern Apennines offers a unique opportunity to reach a complex system of normal faults among which we selected two possible targets. 1) The active Colfiorito fault dipping about 45° toward SW which Tiberina low angle normal fault dipping 15°-25° towards ENE, which moves through a combination of aseismic creep and repeating microearthquakes. Drilling the Colfiorito active fault at a depth of about 2-3 km allows targeting the high coseismic slip patch of the 1997 earthquake M=6 seismogenic structure. Drilling the Alto Tiberina Fault at a depth of nearly 5-6 km will target a micro seismicity source. We aim to collect new original data through borehole logging and sampling and to set up a permanent observatory at depth for a multidisciplinary monitoring to characterize these active normal fault zones. This will allow to understand how such faults behave and to create more realistic models of: earthquake nucleation, seismicity pattern, stress interactions and earthquake triggering at local and regional scale. Both drilling targets present relevant technical issues that should be discussed from different points of view before selecting the starting drilling site

Reduced proficiency in homologous recombination underlies the high sensitivity of embryonal carcinoma testicular germ cell tumors to Cisplatin and poly (adp-ribose) polymerase inhibition

Testicular Germ Cell Tumors (TGCT) and patient-derived cell lines are extremely sensitive to cisplatin and other interstrand cross-link (ICL) inducing agents. Nevertheless, a subset of TGCTs are either innately resistant or acquire resistance to cisplatin during treatment. Understanding the mechanisms underlying TGCT sensitivity/resistance to cisplatin as well as the identification of novel strategies to target cisplatin-resistant TGCTs have major clinical implications. Herein, we have examined the proficiency of five embryonal carcinoma (EC) cell lines to repair cisplatin-induced ICLs. Using γH2AX staining as a marker of double strand break formation, we found that EC cell lines were either incapable of or had a reduced ability to repair ICL-induced damage. The defect correlated with reduced Homologous Recombination (HR) repair, as demonstrated by the reduction of RAD51 foci formation and by direct evaluation of HR efficiency using a GFP-reporter substrate. HR-defective tumors cells are known to be sensitive to the treatment with poly(ADP-ribose) polymerase (PARP) inhibitor. In line with this observation, we found that EC cell lines were also sensitive to PARP inhibitor monotherapy. The magnitude of sensitivity correlated with HR-repair reduced proficiency and with the expression levels and activity of PARP1 protein. In addition, we found that PARP inhibition strongly enhanced the response of the most resistant EC cells to cisplatin, by reducing their ability to overcome the damage. These results point to a reduced proficiency of HR repair as a source of sensitivity of ECs to ICL-inducing agents and PARP inhibitor monotherapy, and suggest that pharmacological inhibition of PARP can be exploited to target the stem cell component of the TGCTs (namely ECs) and to enhance the sensitivity of cisplatin-resistant TGCTs to standard treatments

Testicular germ cell tumors acquire cisplatin resistance by rebalancing the usage of DNA repair pathways

Despite germ cell tumors (GCTs) responding to cisplatin-based chemotherapy at a high rate, a subset of patients does not respond to treatment and have significantly worse prognosis. The biological mechanisms underlying the resistance remain unknown. In this study, by using two TGCT cell lines that have acquired cisplatin resistance after chronic exposure to the drug, we iden-tified some key proteins and mechanisms of acquired resistance. We show that cisplatin-resistant cell lines had a non-homologous end-joining (NHEJ)-less phenotype. This correlated with a reduced basal expression of TP53-binding protein 1 (53BP1) and DNA-dependent protein kinase (DNA-PKcs) proteins and reduced formation of 53BP1 foci after cisplatin treatment. Consistent with these observations, modulation of 53BP1 protein expression altered the cell line’s resistance to cisplatin, and inhibition of DNA-PKcs activity antagonized cisplatin cytotoxicity. Dampening of NHEJ was accompanied by a functional increase in the repair of DNA double-strand breaks (DSBs) by the homologous recombination repair pathway. As a result, cisplatin-resistant cells were more resistant to PARP inhibitor (PARPi) monotherapy. Moreover, when PARPi was given in combination with cisplatin, it exerted an additive/synergistic effect, and reduced the cisplatin dose for cytotoxicity. These results suggest that treatment of cisplatin-refractory patients may benefit from low-dose cis-platin therapy combined with PARPi

Location of chlorogenic acid biosynthesis pathway and polyphenol oxidase genes in a new interspecific anchored linkage map of eggplant

© Gramazio et al.; licensee BioMed Central. 2014. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity

Glycosylated diazeniumdiolates of structure R2NN(O)dNO-R ′ (R ′ ) a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)dNO- ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)dNO-GlcNAc (where R2N) diethylamino or pyrrolidin-l-yl and GlcNAc) N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity