Gases and seabed fluid fluxes at the Panarea shallow hydrothermal vents (Aeolian Islands)

CO2 leaking into the shallow sediments and overlying seawater is partitioned in different forms, each migrating at its own rate and having potentially different impacts. To begin with the CO2 gas will migrate through the shallow subsurface either alone as a free gas or together with associated deep fluids (e.g. brines), with the free-phase CO2 equilibrating with the surrounding pore waters/associated brines. Migrating upward these fluids will enter the base of the water column, with the release of gas bubbles (and possibly associated waters) from the sediments into the overlying seawater. The bubbles will rise in the water column creating what is known as a bubble “flare” with the CO2 in the bubbles dissolving in the surrounding surface water as they rise. Depending on the depth and the chemical/physical characteristics of the water column, these bubbles may or may not reach the water surface. Any co-migrating water/brine will also be released into the water column, creating a plume having a chemical composition that is distinct from the surrounding seawater, consisting of dissolved gases (mainly CO2), elements in the original brine, and elements liberated via CO2-induced water-rock interaction. The height that this dissolved plume will reach in the water column will depend on the original flow rate across the sediment-water interface and the density contrast between the plume and surrounding seawater. Both the gas-induced and water plumes will then migrate laterally and vertically as a result of the local currents, water column stratification, and density effects, meaning that there is the potential for impact both in the near and far field for pelagic organisms, both in terms of a lower pH and the possibility of elevated concentrations of toxic elements. This study was carried out in the framework of two EC funded projects, RISCS and ECO2 related to research on sub-seabed CO2 storage as climate change mitigation strategy, and potential impact on marine ecosystems. Here, we investigated how CO2-leakage, a risk associated with subseafloor CO2-storage, can affect physical and chemical characteristics of the surrounding ecosystem. We studied the Panarea natural laboratory site (Aeolian Islands), where natural CO2 is leaking from the seafloor into the overlying water column, as an analogue for a leakage scenario

Microbial processing of sedimentary organic matter at a shallow LTER site in the northern Adriatic Sea: an 8-year case study

Benthic prokaryotes are the key-players in C-cycling at the sediment-seawater interface, one of the largest biologically active interfaces on Earth. Here, microbial-mediated processes, such as the degradation of organic matter and the incorporation of mobilized C into microbial biomass, depend on several factors such as environmental temperature and substrate availability, especially in shallow sediments at mid-high latitudes where seasonal fluctuations of these variables occur. In the present study, four degradative activities (β-glucosidase, lipase, chitinase and aminopeptidase), Heterotrophic C Production (HCP), Total Organic C (TOC), Total Nitrogen (TN) and Biopolymeric C (BPC) were investigated seasonally from April 2010 to April 2018 in the surface sediments of a shallow Long-Term Ecological Research (LTER) station of the northern Adriatic Sea. Significant temperature-dependences were described by Arrhenius-type equations for HCP and each of the degradative activities tested with the exception of aminopeptidase. The relatively low apparent Activation Energies suggested that these microbial-mediated processes were enhanced by the availability of palatable substrates over the study period. Nevertheless, a clear and tight dependence from such substrates was detected only for aminopeptidase, the most pronounced degradative activity observed. TN was identified by the stepwise multiple regression analysis as the environmental variable that mainly drove this exoenzymatic activity. Enhanced aminopeptidase rates mirrored peaks of TN that seemed, in turn, linked to the seasonal proliferation of benthic microalgae. By supplying prokaryotes with promptly available substrates, these autotrophs, represented mainly by diatoms, seemed to play an important role in the C-cycling regulation at the studied LTER station

Stable carbon isotopes of phytoplankton as a tool to monitor anthropogenic CO2 submarine leakages

This study aims to validate the stable carbon isotopic composition (d13C) of phytoplankton as a tool for detecting submarine leakages of anthropogenic CO2(g), since it is characterised by d13C values significantly lower than the natural CO2 dissolved in oceans. Three culture experiments were carried out to investigate the changes in d13C of the diatom Thalassiosira rotula during growth in an artificially modified medium (ASW). Three different dissolved inorganic carbon (DIC) concentrations were tested to verify if carbon availability affects phytoplankton d13C. Simultaneously, at each experiment, T. rotula was cultured under natural DIC isotopic composition (d13C DIC) and carbonate system conditions. The available DIC pool for diatoms grown in ASW was characterised by d13C DIC values (-44.2 ± 0.9‰) significantly lower than the typical marine range. Through photosynthetic DIC uptake, microalgae d13C rapidly changed, reaching significantly low values (until -43.4‰). Moreover, the different DIC concentrations did not affect the diatom d13C, exhibiting the same trend in d13C values in the three ASW experiments. The experiments prove that phytoplankton isotopic composition quickly responds to changes in the d13C of the medium, making this approach a promising and low-impact tool for detecting CO2(g) submarine leakages from CO2(g) deposits

Azetidin-2-one-based small molecules as dual hHDAC6/HDAC8 inhibitors: Investigation of their mechanism of action and impact of dual inhibition profile on cell viability

The search of new therapeutic tools for the treatment of cancer is being a challenge for medicinal chemists. Due to their role in different pathological conditions, histone deacetylase (HDAC) enzymes are considered valuable therapeutic targets. HDAC6 is a well-investigated HDAC-class IIb enzyme mainly characterized by a cytoplasmic localization; HDAC8 is an epigenetic eraser, unique HDAC-class I member that displays some aminoacidic similarity to HDAC6. New polypharmacological agents for cancer treatment, based on a dual hHDAC6/hHDAC8 inhibition profile were developed. The dual inhibitor design investigated the diphenyl-azetidin-2-one scaffold, typified in three different structural families, that, combined to a slender benzyl linker (6c, 6i, and 6j), displays nanomolar inhibition potency against hHDAC6 and hHDAC8 isoforms. Notably, their selective action was also corroborated by measuring their low inhibitory potency towards hHDAC1 and hHDAC10. Selectivity of these compounds was further demonstrated in human cell-based western blots experiments, by testing the acetylation of the non-histone substrates alpha-tubulin and SMC3. Furthermore, the compounds reduced the proliferation of colorectal HCT116 and leukemia U937 cells, after 48 h of treatment. The toxicity of the compounds was evaluated in rat perfused heart and in zebrafish embryos. In this latter model we also validated the efficacy of the dual hHDAC6/hHDAC8 inhibitors against their common target acetylated-alpha tubulin. Finally, the metabolic stability was verified in rat, mouse, and human liver microsomes

Selective fatty acid amide hydrolase inhibitors as potential novel antiepileptic agents

Temporal lobe epilepsy is the most common form of epilepsy, and current antiepileptic drugs are ineffective in many patients. The endocannabinoid system has been associated with an on-demand protective response to seizures. Blocking endocannabinoid catabolism would elicit antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation of the hippocampal maximal dentate activation. Notably, 2a did not affect hippocampal dentate gyrus long-term synaptic plasticity. These data prompted our further endeavor aiming at discovering new antiepileptic agents, developing a new set of FAAH inhibitors (3a–m). Biological studies highlighted 3h and 3m as the best performing analogues to be further investigated. In cell-based studies, using a neuroblastoma cell line, 3h and 3m could reduce the oxinflammation state by decreasing DNA-binding activity of NF-kB p65, devoid of cytotoxic effect. Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a

Carbon cycle in marine systems under different anthropogenic pressure

During the past two centuries, human activities have greatly modified the exchange of carbon and nutrients between land, atmosphere, freshwater bodies, coastal zones and open ocean. This PhD thesis focuses on different aspects of carbon cycle, considering three case study for the evaluation of the effects of anthropogenic pressure and of the natural evolution of carbon cycle. The first case study focuses on anthropogenic impacts on contaminated coastal areas. These environments connect terrestrial and oceanic systems, and are highly subjected to anthropogenic pressure. An example of a contaminated coastal area is the Mar Piccolo of Taranto (Ionian Sea) and the results of two published papers are reported. In the first paper, the results of the analysis of nutrients and carbon fluxes at sediment-water interface showed that the multi-contamination of both inorganic and organic pollutants in the sediments is potentially transferable to the water column and to the aquatic trophic chain. On the other hand, in the second paper, the results of the analysis of a long time series of chemical-physical characteristics of the water column highlighted that the implementation of sewage treatment plants has positively affected the trophic status of the Mar Piccolo from being relatively eutrophic to moderately oligotrophic. The increase of atmospheric CO2 concentration has been recognised as one of the main causes of climate change. Carbon capture and storage technology (CCS) is expected to play a key role among mitigation strategies by reducing CO2 emissions into atmosphere from fossil fuel combustion. Although leakages from well-engineered storage sites are not expected, the environmental impacts related to potential CO2 seepages are a major issue for the acceptance of this approach and should be carefully monitored. Since different carbon sources have different \u3b413C values, the aim of the second case study is the evaluation of phytoplankton stable carbon isotopes as a tool for effective early warning of CO2 leakage from CCS. Two culture experiments were conducted under controlled conditions for monitoring \u3b413C changes in the diatom Thalassiosira rotula during growth in two different media. The isotopic composition of microalgae grown in natural seawater (NAT) was compared to that of diatoms grown in an artificial seawater (ASW), supplied with industrial CO2 and characterised by strongly 13C-depleted dissolved inorganic carbon values. The uptake of inorganic carbon in ASW resulted in a rapid and significant change in microalgae \u3b413C values, whereas in NAT phytoplankton \u3b413C did not show important deviations from the starting value, confirming the effectiveness of phytoplankton \u3b413C as a tool for detecting different CO2 sources. The third case study aims at a better understanding of carbon cycle, as the rate of changes not only depends on human activities, but also on natural biogeochemical processes. Marine dissolved organic matter (DOM) plays a crucial role in oceanic carbon storage, and the extent of its contribution on carbon sequestration depends on its bioavailability. In this study, a plug-flow bioreactor approach has been tested in order to evaluate DOM availability for microbial community in the Gulf of Trieste (Northern Adriatic Sea) by the analysis of dissolved organic carbon (DOC), nitrogen (DON) and phosphorus (DOP) degradation and nutrient uptake. The bioreactor approach confirmed to be useful for bioavailable DOC assessment, but further research is needed for confirming its effectiveness for defining DON and DOP bioavailability and nutrient utilisation

A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds

CD44 is emerging as an important receptor biomarker for various cancers. Amongst these is oral cancer, where surgical resection remains an essential mode of treatment. Unfortunately, surgery is frequently associated with permanent disfigurement, malnutrition, and functional comorbidities due to the difficultly of tumour removal. Optical imaging agents that can guide tumour tissue identification represent an attractive approach to minimising the impact of surgery. Here, we report the synthesis of a water-soluble fluorescent probe, namely HA-FA-HEG-OE (compound 1), that comprises components originating from natural sources: oleic acid, ferulic acid and hyaluronic acid. Compound 1 was found to be non-toxic, displayed aggregation induced emission and accumulated intracellularly in vesicles in SCC-9 oral squamous cells. The uptake of 1 was fully reversible over time. Internalization of compound 1 occurs through receptor mediated endocytosis; uniquely mediated through the CD44 receptor. Uptake is related to tumorigenic potential, with non-tumorigenic, dysplastic DOK cells and poorly tumorigenic MCF-7 cells showing only low intracellular levels and highlighting the critical role of endocytosis in cancer progression and metastasis. Together, the recognised importance of CD44 as a cancer stem cell marker in oral cancer, and the reversible, non-toxic nature of 1, makes it a promising agent for real time intraoperative imaging

Retinitis Pigmentosa and Retinal Degenerations: Deciphering Pathways and Targets for Drug Discovery and Development

Inherited retinal diseases (IRDs) are a group of retinopathies generally caused by genetic mutations. Retinitis pigmentosa (RP) represents one of the most studied IRDs. RP leads to intense vision loss or blindness resulting from the degeneration of photoreceptor cells. To date, RP is mainly treated with palliative supplementation of vitamin A and retinoids, gene therapies, or surgical interventions. Therefore, a pharmacologically based therapy is an urgent need requiring a medicinal chemistry approach, to validate molecular targets able to deal with retinal degeneration. This Review aims at outlining the recent research efforts in identifying new drug targets for RP, especially focusing on the neuroprotective role of the Wnt/β-catenin/GSK3β pathway and apoptosis modulators (in particular PARP-1) but also on growth factors such as VEGF and BDNF. Furthermore, the role of spatiotemporally expressed G protein-coupled receptors (GPR124) in the retina and the emerging function of histone deacetylase inhibitors in promoting retinal neuroprotection will be discussed