Sediment transport and deposition during extreme sea storm events at the Salerno Bay (Tyrrhenian Sea): comparison of field data with numerical model results

Seismic stratigraphy and core litho-stratigraphy in the Salerno Bay inner shelf (Southern Tyrrhenian Sea) reveal significant storm deposition episodes over the last 1 ky. Three major events are preserved as decimetre thick silt/sand layers bounded at their base by erosional surfaces and sealed in the muddy marine sequences between 25 and 60 m of depth. Geochronology and chrono-stratigraphy on core sediment point towards a recurrence of major sea storms between 0.1 and 0.3 ky and put the last significant event in the 19th century, when no local meteorological time series is available. A modelling of extreme sea-storms with a return period of about 0.1 ky is here proposed based on historical hindcast and aims at explaining the occurrence of such unusual deep and thick sand deposits in the northern sector of the bay. Results highlight the vulnerability of the northern coast of the Salerno Bay to the south western sea storms which can drive waves up to about 8 m high and wave period of about 13 s. With these conditions an intense combined flow current is formed and might account for winnowing fine sand down to the depth of 40 m at least. The numerical model thus confirms a possible sand transport in the bottom boundary layer due to wave-current interaction and could corroborate the interpretation of the most recent sand layers, included in the cores, as being generated under extreme sea storm conditions

The geological record of storm events over the last 1000 years in the Salerno Bay (Southern Tyrrhenian Sea): new proxy evidences

International audienceThe shallow marine Late Holocene wedge of the northern Salerno Bay shelf (Southern Tyrrhenian Sea) discloses the presence of four decimetric shelf-tapering sand beds. Their internal features, depicted by cores analysis and their stratigraphic position, revealed by VHR seismic investigations, inferred sandy layers as being the result of flash deposition, storm controlled, thus episodic. Stratigraphic correlations among cores lead to constrain sandy layers deposition to storm events falling in the 11th, 16th, 19th and 20th centuries. A certain attribution of the most recent event bed to the major cloudburst that hit the Salerno region in 1954A.D. and resulted in a disastrous flood of the Bonea stream, was formerly achieved. A tentative link with two sea-storms that occurred in the 1544A.D. and in the 1879A.D. and well documented by historical sources is here proposed to explain the deposition of the two previous event beds. The deposition of these sandy layers must be related to major storm events, since their preservation in the stratigraphic record is not common. Lithostratigraphic and textural differences between flood and sea-storm emplacement emerge from the study of sandy layers in cores and point to a prevalence of sea-storm deposits in the middle shelf compared to flood deposits. Seismic stratigraphic evidence lead us to suppose that the style of episodic flash deposition has been running on for the last 2-3kyr and is probably linked to a climatic trend of the region

HDAC inhibition potentiates immunotherapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) represents a more aggressive and difficult subtype of breast cancer where responses to chemotherapy occur, but toxicity is significant and resistance often follows. Immunotherapy has shown promising results in various types of cancer, including breast cancer. Here, we investigated a new combination strategy where histone deacetylase inhibitors (HDACi) are applied with immune checkpoint inhibitors to improve immunotherapy responses in TNBC. Testing different epigenetic modifiers, we focused on the mechanisms underlying HDACi as priming modulators of immunotherapy. Tumor cells were co-cultured with human peripheral blood mononuclear cells (PBMCs) and flow cytometric immunophenotyping was performed to define the role of epigenetic priming in promoting tumor antigen presentation and immune cell activation. We found that HDACi up-regulate PD-L1 mRNA and protein expression in a time-dependent manner in TNBC cells, but not in hormone responsive cells. Focusing on TNBC, HDACi up-regulated PD-L1 and HLA-DR on tumor cells when co-cultured with PBMCs and down-regulated CD4+ Foxp3+ Treg in vitro. HDACi significantly enhanced the in vivo response to PD-1/CTLA-4 blockade in the triple-negative 4T1 breast cancer mouse model, the only currently available experimental system with functional resemblance to human TNBC. This resulted in a significant decrease in tumor growth and increased survival, associated with increased T cell tumor infiltration and a reduction in CD4+ Foxp3+ T cells in the tumor microenvironment. Overall, our results suggest a novel role for HDAC inhibition in combination with immune checkpoint inhibitors and identify a promising therapeutic strategy, supporting its further clinical evaluation for TNBC treatment

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

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

Environment and bladder cancer: molecular analysis by interaction networks

Bladder cancer (BC) is the 9th most common cancer worldwide, and the 6th most common cancer in men. Its development is linked to chronic inflammation, genetic susceptibility, smoking, occupational exposures and environmental pollutants. Aim of this work was to identify a sub-network of genes/proteins modulated by environmental or arsenic exposure in BC by computational network approaches. Our studies evidenced the presence of HUB nodes both in “BC and environment” and “BC and arsenicals” networks. These HUB nodes resulted to be correlated to circadian genes and targeted by some miRNAs already reported as involved in BC, thus suggesting how they play an important role in BC development due to environmental or arsenic exposure. Through data-mining analysis related to putative effect of the identified HUB nodes on survival we identified genes/proteins and their mutations on which it will be useful to focus further experimental studies related to the evaluation of their expression in biological matrices and to their utility as biomarkers of BC developmen

Detection of heat and cold waves in Montevergine time series (1884–2015)

Abstract. In recent years, extreme events related to cooling and heating have taken high resonance, motivating the scientific community to carry out an intensive research activity, aimed to detect their variability and frequency. In this work, we have investigated about the frequency, the duration, the severity and the intensity of heat and cold waves in a Southern Italy high-altitude region, by analysing the climatological time series collected in Montevergine observatory. Following the guidelines provided by CLIVAR project (Climate and Ocean Variability, Predictability and Change), we have adopted indicators based on percentiles and duration to define a heat wave and cold event. Main results have highlighted a strong and significant positive trend in the last 40 years (1974–2015) in heat waves frequency, severity and intensity. On the contrary, in recent decades, cold wave events have exhibited a significant and positive trend only in intensity. Moreover, through the usage of two Wavelet Analysis tools, the Cross Wavelet Transform and the Wavelet Coherence, we have investigated about the connections between the extreme temperature events occurred in Montevergine and the large-scale atmospheric patterns. The heat wave events have exhibited relevant relationships with the Western European Zonal Circulation and the North Atlantic Oscillation, whereas the variability of cold wave events have shown linkages with the Eastern Mediterranean Pattern and the North Sea Caspian Pattern. In addition, the main features of synoptic patterns that have caused summer heat waves and winter cold waves in Montevergine site are presented