The composite dataset of the present-day Infralittoral Prograding Wedges (IPWs) in the inner continental shelf of the Campania region (Central-Eastern Tyrrhenian Sea)

This article reports on the dataset gathered following the census of 83 present-day Infralittoral Prograding Wedges (IPWs), surveyed on the inner continental shelf of the Central-Eastern Tyrrhenian Sea. The purpose of the census was to explore their bathymetric range and assess the observational laws governing this variability. The ensued dataset (Campania Region IPW Dataset, CRID) includes geographic, topographic and morpho-bathymetric indices, descriptive of each IPW and more, the exposure of each IPW to wave forcing (Geographical fetch, Effective fetch and extreme significant wave height, HS). In this work, histograms contribute to describe all the variables and highlight the dominant features of each IPW. Location maps univocally links the geographic position of each IPW to the appropriate attribute record in the dataset. Further, thematic maps illustrate eight wave fields obtained by offshore-to-nearshore transformation by as many sea states scenarios with 200-year return period. Such wave fields are used as sources for significant wave height representing wave conditions over each IPW. This dataset could be implemented with new measures at a broader scale, by following analogue procedures for measurements, to enlarge the observational scale on IPWs and improve the numerical models which might eventually derive by the analysis of this dataset

Phytoplankton blooms during austral summer in the Ross Sea, Antarctica: Driving factors and trophic implications

During the austral summer of 2014, an oceanographic cruise was conducted in the Ross Sea in the framework of the RoME (Ross Sea Mesoscale Experiment) Project. Forty-three hydrological stations were sampled within three different areas: the northern Ross Sea (RoME 1), Terra Nova Bay (RoME 2), and the southern Ross Sea (RoME 3). The ecological and photophysiological characteristics of the phytoplankton were investigated (i.e., size structure, functional groups, PSII maximum quantum efficiency, photoprotective pigments), as related to hydrographic and chemical features. The aim was to identify the mechanisms that modulate phytoplankton blooms, and consequently, the fate of organic materials produced by the blooms. The observed biomass standing stocks were very high (e.g., integrated chlorophyll-a up to 371 mg m-2 in the top 100 m). Large differences in phytoplankton community composition, relative contribution of functional groups and photosynthetic parameters were observed among the three subsystems. The diatoms (in different physiological status) were the dominant taxa in RoME 1 and RoME 3; in RoME 1, a post-bloom phase was identified, whereas in RoME 3, an active phytoplankton bloom occurred. In RoME 2, diatoms co-occurred with Phaeocystis antarctica, but were vertically segregated by the upper mixed layer, with senescent diatoms dominating in the upper layer, and P. antarctica blooming in the deeper layer. The dominance of the phytoplankton micro-fraction over the whole area and the high Chl-a suggested the prevalence of non-grazed large cells, independent of the distribution of the two functional groups. These data emphasise the occurrence of significant temporal changes in the phytoplankton biomass in the Ross Sea during austral summer. The mechanisms that drive such changes and the fate of the carbon production are probably related to the variations in the limiting factors induced by the concurrent hydrological modifications to the Ross Sea, and they remain to be fully clarified. The comparison of conditions observed during summer 2014 and those reported for previous years reveal considerably different ecological assets that might be the result of current climate change. This suggests that further changes can be expected in the future, even at larger oceanic scales

Modulation of thymidilate synthase and p53 expression by HDAC inhibitor vorinostat resulted in synergistic antitumor effect in combination with 5FU or raltitrexed.

Despite the introduction of several novel anticancer agents almost 50% of colorectal cancer (CRC) patients die for cancer suggesting the necessity of new therapeutical approaches. In this study we demonstrated that the HDAC inhibitor vorinostat exerted potent antiproliferative effect in a panel of mut- and wt-p53 human CRC cell lines. Moreover, in combination with 5-fluorouracil modulated by folinic acid (5FU-FA) or with Raltitrexed (RTX), both commonly used in the treatment of this disease, it showed a clear schedule-dependent synergistic antiproliferative interaction as demonstrated by calculating combination indexes. Only simultaneous, or 24 h pretreatment with vorinostat followed by either agent, produced synergistic effect paralleled by evident cell cycle perturbations with major S-phase arrest. Moreover, we provided for the first time evidences that vorinostat can overcome resistance to both 5FU and RTX. Downmodulation of Thymidilate synthase (TS) protein induced by vorinostat within 24 h, represented a key factor in enhancing the effects of both drugs in sensitive as well as resistant tumor cells. Furthermore, p53, whose wild-type expression is critical for sensitivity to 5FU and RTX, was upregulated by vorinostat in wt- and downregulated in mut-p53 cells, suggesting an additional mechanism of the antiproliferative synergistic interactions observed. Overall these data add new insights in the mechanism of vorinostat antitumor effect and suggested that the association of vorinostat plus 5FU-FA and/or RTX should be clinically explored

Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles

Colon cancer is one of the leading causes of cancer-related death worldwide and the therapy with 5-fluorouracil (5-FU) is mainly limited due to resistance. Recently, we have demonstrated that nucleolar stress upon 5-FU treatment leads to the activation of ribosome-free rpL3 (L3) as proapoptotic factor. In this study, we analyzed L3 expression profile in colon cancer tissues and demonstrated that L3 mRNA amount decreased with malignant progression and the intensity of its expression was inversely related to tumor grade and Bcl-2/Bax ratio. With the aim to develop a combined therapy of 5-FU plus plasmid encoding L3 (pL3), we firstly assessed the potentiation of the cytotoxic effect of 5-FU on colon cancer cells by L3. Next, 10 μM 5-FU and 2 μg of pL3 were encapsulated in biocompatible nanoparticles (NPs) chemically conjugated with HA to achieve active tumor-targeting ability in CD44 overexpressing cancer cells. We showed the specific intracellular accumulation of NPs in cells and a sustained release for 5-FU and L3. Analysis of cytotoxicity and apoptotic induction potential of combined NPs clearly showed that the 5-FU plus L3 were more effective in inducing apoptosis than 5-FU or L3 alone. Furthermore, we show that the cancer-specific chemosensitizer effect of combined NPs may be dependent on L3 ability to affect 5-FU efflux by controlling P-gp (P-glycoprotein) expression. These results led us to propose a novel combined therapy with the use of 5-FU plus L3 in order to establish individualized therapy by examining L3 profiles in tumors to yield a better clinical outcomes

Open-slope, translational submarine landslide in a tectonically active volcanic continental margin (Licosa submarine landslide, southern Tyrrhenian Sea)

The southern Tyrrhenian continental margin is the product of Pliocene-Recent back-arc extension. An area of approximately 30 km of gentle (about 1.5°) lower slope of the last glacial outer shelf sedimentary wedge in water depths of between 200 and 300 m failed between 14 and 11 ka BP. We approached the landslide by multibeam and sub-bottom profiler surveying, high-resolution multichannel seismics, and coring for stratigraphic and geotechnical purposes. With regard to a slope-stability analysis, we carried out an assessment of the stratigraphic and structural setting of the area of the Licosa landslide. This analysis revealed that the landslide detached along a marker bed that was composed of the tephra layer Y-5 (c. 39 ka). Several previously unknown geological characteristics of the area are likely to have affected the slope stability. These are the basal erosion of the slope in the Licosa Channel, a high sedimentation rate in the sedimentary wedge, earthquake shaking, the volcanic ash nature of the detachment surface, subsurface gas/fluid migration, and lateral porewater flow from the depocentre of wedge to the base of the slope along the high-permeability ash layers. A newly discovered prominent structural discontinuity is identified as the fault whose activity may have triggered the landslide

Biotin-targeted Pluronic® P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells

With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic1 P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic1 F127 was conjugated with biotin, while Pluronic1 P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein-rich media and improved cytotoxicity in A549 cells as compared to free NCL (P < 0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin- decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance

HDAC class I inhibitor domatinostat sensitizes pancreatic cancer to chemotherapy by targeting cancer stem cell compartment via FOXM1 modulation

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet clinical need due to the very poor prognosis and the lack of effective therapy. Here we investigated the potential of domatinostat (4SC-202), a new class I histone deacetylase (HDAC) inhibitor, currently in clinical development, to sensitize PDAC to first line standard gemcitabine (G)/taxol (T) doublet chemotherapy treatment. Methods: Synergistic anti-tumor effect of the combined treatment was assessed in PANC1, ASPC1 and PANC28 PDAC cell lines in vitro as well as on tumor spheroids and microtissues, by evaluating combination index (CI), apoptosis, clonogenic capability. The data were confirmed in vivo xenograft models of PANC28 and PANC1 cells in athymic mice. Cancer stem cells (CSC) targeting was studied by mRNA and protein expression of CSC markers, by limiting dilution assay, and by flow cytometric and immunofluorescent evaluation of CSC mitochondrial and cellular oxidative stress. Mechanistic role of forkhead box M1 (FOXM1) and downstream targets was evaluated in FOXM1-overexpressing PDAC cells. Results: We showed that domatinostat sensitized in vitro and in vivo models of PDAC to chemotherapeutics commonly used in PDAC patients management and particularly to GT doublet, by targeting CSC compartment through the induction of mitochondrial and cellular oxidative stress. Mechanistically, we showed that domatinostat hampers the expression and function of FOXM1, a transcription factor playing a crucial role in stemness, oxidative stress modulation and DNA repair. Domatinostat reduced FOXM1 protein levels by downregulating mRNA expression and inducing proteasome-mediated protein degradation thus preventing nuclear translocation correlated with a reduction of FOXM1 target genes. Furthermore, by overexpressing FOXM1 in PDAC cells we significantly reduced domatinostatinducing oxidative mitochondrial and cellular stress and abolished GT sensitization, both in adherent and spheroid cells, confirming FOXM1 crucial role in the mechanisms described. Finally, we found a correlation of FOXM1 expression with poor progression free survival in PDAC chemotherapy-treated patients

Campagna Oceanografica Sismica Magnetica Elettrica Ischia (COSMEI)

La Campagna Oceanografica Sismica Magnetica Elettrica Ischia (denominata "COSMEI") è nata a seguito dell'evento sismico verificatosi alle 20:57 del 21 agosto 2017 Mw 3.9 con epicentro nell'area di Casamicciola, con lo scopo di fornire ulteriori contributi nell'individuazione di strutture vulcano-tettoniche attive nel settore nord marino dell'isola d'Ischia. Il CNR-DTA nell'ambito di tali attività ed in concomitanza delle attività del Centro per la Microzonazione Sismica e delle sue applicazioni (centro MS), ha disposto un piano di indagini a mare necessarie per la ricostruzione di strutture tettoniche e vulcaniche potenzialmente origine di eventi sismici. La campagna oceanografica COSMEI dell'IAMC-CNR di Napoli, ha predisposto rilievi geofisici di tipo sismico multicanale, magnetico differenziale, di resistività elettrica, Chirp e Multibeam nel settore marino nord-orientale dell'isola d'Ischia. Le attività di acquisizione sono state condotte utilizzando la N/O Minerva Uno del Consiglio Nazionale delle Ricerche (CNR). L'obiettivo finale di tale studio è quello di fornire nuovi elementi geofisici finalizzati a migliorare la conoscenza dell'evoluzione geologica di questo settore dell'isola. In tale contesto, l'interpretazione geologico-strutturale dei profili sismici multicanale combinata col dato magnetometrico e di resistività elettrica ha lo scopo di migliorare la conoscenza dell’area nord-orientale dell'isola che risulta controllata da complessi vulcano-tettonici

Seabed mapping in the Pelagie Islands marine protected area (Sicily Channel, southern Mediterranean) using Remote Sensing Object Based Image Analysis (RSOBIA)

In this paper we present the seabed maps of the shallow-water areas of Lampedusa and Linosa, belonging to the Pelagie Islands Marine Protected Area. Two surveys were carried out (“Lampedusa 2015” and “Linosa 2016”) to collect bathymetric and acoustic backscatter data through the use of a Reson SeaBat 7125 high-resolution multibeam system. Ground-truth data, in the form of grab samples and diver video-observations, were also collected during both surveys. Sediment samples were analyzed for grain size, while video images were analyzed and described revealing the acoustic seabed and other bio-physical characteristics. A map of seabed classification, including sediment types and seagrass distribution, was produced using the tool Remote Sensing Object Based Image Analysis (RSOBIA) by integrating information derived from backscatter data and bathy-morphological features, validated by ground-truth data. This allows to create a first seabed maps (i.e. benthoscape classification), of Lampedusa and Linosa, at scale 1:20 000 and 1:32 000, respectively, that will be checked and implemented through further surveys. The results point out a very rich and largely variable marine ecosystem on the seabed surrounding the two islands, with the occurrence of priority habitats, and will be of support for a more comprehensive maritime spatial planning of the Marine Protected Area

Valproic Acid Synergizes With Cisplatin and Cetuximab in vitro and in vivo in Head and Neck Cancer by Targeting the Mechanisms of Resistance

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus cetuximab (CX) is one of the standard first-line treatments in this disease. However, this therapeutic regimen is often associated with high toxicity and resistance, suggesting that new combinatorial strategies are needed to improve its therapeutic index. In our study, we evaluated the antitumor effects of valproic acid (VPA), a well-known antiepileptic agent with histone deacetylase inhibitory activity, in combination with CDDP/CX doublet in head and neck squamous cell carcinoma (HNSCC) models. We demonstrated, in HNSCC cell lines, but not in normal human fibroblasts, that simultaneous exposure to equitoxic doses of VPA plus CDDP/CX resulted in a clear synergistic antiproliferative and pro-apoptotic effects. The synergistic antitumor effect was confirmed in four different 3D-self-assembled spheroid models, suggesting the ability of the combined approach to affect also the cancer stem cells compartment. Mechanistically, VPA enhanced DNA damage in combination treatment by reducing the mRNA expression of ERCC Excision Repair 1, a critical player in DNA repair, and by increasing CDDP intracellular concentration via upregulation at transcriptional level of CDDP influx channel copper transporter 1 and downregulation of the ATPAse ATP7B involved in CDDP-export. Valproic acid also induced a dose-dependent downregulation of epidermal growth factor receptor (EGFR) expression and of MAPK and AKT downstream signaling pathways and prevent CDDP- and/or CX-induced EGFR nuclear translocation, a well-known mechanism of resistance to chemotherapy. Indeed, VPA impaired the transcription of genes induced by non-canonical activity of nuclear EGFR, such as cyclin D1 and thymidylate synthase. Finally, we confirmed the synergistic antitumor effect also in vivo in both heterotopic and orthotopic models, demonstrating that the combined treatment completely blocked HNSCC xenograft tumors growth in nude mice. Overall, the introduction of a safe and generic drug such as VPA into the conventional treatment for R/M HNSCC represents an innovative and feasible antitumor strategy that warrants further clinical evaluation. A phase II clinical trial exploring the combination of VPA and CDDP/CX in R/M HNSCC patients is currently ongoing in our institute