111 research outputs found

    Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels

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    Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe(2+)-loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe(2+) uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe(2+) through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H' protein and some of its variants as case studies. We describe the structural features that determine Fe(2+) translocation with atomistic detail, and we propose a putative mechanism for Fe(2+) transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin

    Statistical moments of power spectrum: a fast tool for the classification of seismic events recorded on volcanoes

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    Abstract. Spectral analysis has been applied to almost thousand seismic events recorded at Vesuvius volcano (Naples, southern Italy) in 2018 with the aim to test a new tool for a fast event classification. We computed two spectral parameters, central frequency and shape factor, from the spectral moments of order 0, 1, and 2, for each event at seven seismic stations taking the mean among the three components of ground motion. The analyzed events consist of volcano-tectonic earthquakes, low frequency events and unclassified events (landslides, rockfall, thunders, quarry blasts, etc.). Most of them are of low magnitude, and/or low maximum signal amplitude, therefore the signal to noise ratio is very different between the low noise summit stations and the higher noise stations installed at low elevation around the volcano. The results of our analysis show that volcano-tectonic earthquakes and low frequency events are easily distinguishable through the spectral moments values, particularly at seismic stations closer to the epicenter. On the contrary, unclassified events show the spectral parameters values distributed in a broad range which overlap both the volcano-tectonic earthquakes and the low frequency events. Since the computation of spectral parameters is extremely easy and fast for a detected event, it may become an effective tool for event classification in observatory practice

    Aerobic Microbial Inactivation Kinetics of Shrimp Using a Fixed Minimal Ozone Discharge: A Fact or Fib During Iced Storage?

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    AbstractAmong researchers worldwide, the combination of preservation methods aimed to achieve improved effects on microbial inactivation of seafood products is an area of research receiving increasing interest. Globally also, the demand for high quality minimally processed food products are on the increase. Ozone treatment, three decade – long declared 'Generally Recognized As Safe' and approved as food contact sanitizing agent has evolved up to recent times where it assumes the likes of domestic food-processing facilities manufactured with environment-friendly status ensuring consumer safety. On the other hand, the subject of inactivation kinetics of seafood microorganisms following ozone treatment is still under debate. Furthermore, kinetic models remain the economical and quick approach to predict the preservation parameters. Nevertheless, there is paucity of information regards aerobic microbial inactivation of crustacean product arising from fixed minimal ozone discharge. Is the phenomenon of aerobic microbial inactivation kinetics of shrimp product subject to a fixed minimal ozone discharge during iced storage a fact or fib? To answer this, the aerobic microbial inactivation kinetics of shrimp during iced storage of up to 11 days was inspected. The process conditions comprised of a fixed ozone concentration of 100mg/h minimally discharged at wash time of 1min as well as iced storage of up to 11 days. Minimal ozone treatment was applied either prior to or during iced storage situations. Aerobic microbial inactivation presented significant effects during iced storage (P<0.05). Line of fit that could best describe the aerobic microbial inactivation kinetics showed adequacy only at the fourth order of storage time 'x' variable, which could only but account for between 75 - 96% of explained variance. Overall, aerobic microbial inactivation kinetics of shrimp using a fixed minimal ozone discharge appears quantitatively possible even though it decreases as iced storage progresses

    Length-Weight Relationships of 52 Species from the South of Sicily (Central Mediterranean Sea)

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    The Length-Weight relationships (LWRs) of 52 species (14 never reported before) of fishes, crustaceans and cephalopods living on the shelf and upper slope off Southern Sicily are provided. Data were collected in the framework of the International bottom trawl survey in the Mediterranean (MEDITS) in the South of Sicily (Central Mediterranean), covering a time frame ranging from 2012 to 2019. Linear regressions were significant for all species (p &lt; 0.05) with R-2 values ranging from 0.86 to 0.99. The intercept (a) of LWRs ranged from 0.0003 to 0.4677, while the slope (b) ranged from 2.1281 to 3.306. The Welch t-test, used to evaluate differences between the obtained LWRs with those reported in the literature, revealed that most of the LWRs (about 55%) reported in this study are in disagreement with those obtained previously by other authors from the Strait of Sicily. It is expected that the results obtained from this study will contribute to filling the knowledge gap of fish populations in this area and also assist fisheries scientists in future stock assessment studies

    Exploring the feasibility of technological transfers of two by-catch reduction devices in the crustacean bottom trawling of the central Mediterranean

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    Introduction: Most Mediterranean fish stocks are overexploited owing to high fishing efforts and poor exploitation patterns. Demersal trawl fisheries are considered the most impactful fishery type because of the high quantities of unwanted catch that is then routinely discarded at sea. Methods: In the present study, two types of by-catch reduction devices (BRDs), that is a sorting grid (Grid-T45 40 mm) and a T90 50 mm codend, were compared to a typical commercial bottom trawl net (control) in terms of size structures and catch per unit effort to assess the effect of gear modification on the selectivity of crustacean fisheries in the central Mediterranean Sea. In particular, three randomly selected trawlers were involved in a paired hauls experiment fishing at the same time in the same fishing ground. Each trawler carried out four hauls per day during a 3-day campaign for a total of 36 hauls. The target species of the fishery is Parapenaeus longirostris (herein DPS), and the main commercial by-catch is Merluccius merluccius (herein HKE). Results: The results showed that the landing per unit effort (LPUE) of DPS was higher for Grid-T45 40 mm net, although it did not differ significantly from that of the control net. Conversely, the discard per unit effort (DPUE) of the control net was significantly higher than of both BRD configurations. For HKE, a slightly higher LPUE was recorded using the T90 50 mm codend compared to that of the control, but this result was not statistically significant. The lowest DPUE was found for the T90 50 mm codend, with significant differences compared to that of the control and Grid-T45 40 mm net. The catch comparison of the size structures analysed through generalised linear mixed models highlighted that the Grid-T45 40 mm net was more effective in catching adult DPS, whereas the T90 50 mm codend was more selective for adult HKE Discussion: In conclusion, although further studies should be carried out in future to test the performance of the BRDs in different areas and seasons, the investigated gear seems to be promising for reducing the catch of undersized individuals and contributing to mitigating the current overfishing of DPS and HK

    Confirmed Activity and Tolerability of Weekly Paclitaxel in the Treatment of Advanced Angiosarcoma

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    Background. In several prospective and retrospective studies, weekly paclitaxel showed promising activity in patients with angiosarcoma. Patients and Methods. Our study was originally designed as a prospective, phase II multicenter trial for patients younger than 75, with ECOG performance status 0–2, affected by locally advanced or metastatic angiosarcoma. Patients received paclitaxel 80 mg/m2 intravenously, at days 1, 8, and 15 every 4 weeks, until disease progression or unacceptable toxicity. Primary endpoint was objective response. Results. Eight patients were enrolled but, due to very slow accrual, the trial was prematurely stopped and further 10 patients were retrospectively included in the analysis. Out of 17 evaluable patients, 6 patients obtained an objective response (5 partial, 1 complete), with an objective response rate of 35% (95% confidence interval 17%–59%). Of note, five responses were obtained in pretreated patients. In the paper, details of overall survival, progression-free survival, and tolerability are reported. Conclusions. In this small series of patients with locally advanced or metastatic angiosarcoma, weekly paclitaxel was confirmed to be well tolerated and active even in pretreated patients

    All is fish that comes to the net: metabarcoding for rapid fisheries catch assessment

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    Monitoring marine resource exploitation is a key activity in fisheries science and biodiversity conservation. Since research surveys are time‐consuming and costly, fishery‐dependent data (i.e. derived directly from fishing vessels) are increasingly credited with a key role in expanding the reach of ocean monitoring. Fishing vessels may be seen as widely ranging data‐collecting platforms, which could act as a fleet of sentinels for monitoring marine life, in particular exploited stocks. Here, we investigate the possibility of assessing catch composition of single hauls carried out by trawlers by applying DNA metabarcoding to the dense water draining from fishing nets just after the end of hauling operations (hereafter ‘slush’). We assess the performance of this approach in portraying β‐diversity and examining the quantitative relationship between species abundances in the catch and DNA amount in the slush (read counts generated by amplicon sequencing). We demonstrate that the assemblages identified using DNA in the slush satisfactorily mirror those returned by visual inspection of net content (about 71% of species and 86% of families of fish) and detect a strong relationship between read counts and species abundances in the catch. We therefore argue that this approach could be upscaled to serve as a powerful source of information on the structure of demersal assemblages and the impact of fisheries

    Regulation of HuR structure and function by dihydrotanshinone-I

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    The Human antigen R protein (HuR) is an RNA-binding protein that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, and post-transcriptionally regulates the fate of target RNAs. The natural product dihydrotanshinone-I (DHTS) prevents the association of HuR and target RNAs in vitro and in cultured cells by interfering with the binding of HuR to RNA. Here, we report the structural determinants of the interaction between DHTS and HuR and the impact of DHTS on HuR binding to target mRNAs transcriptome-wide. NMR titration and Molecular Dynamics simulation identified the residues within RRM1 and RRM2 responsible for the interaction between DHTS and HuR. RNA Electromobility Shifts and Alpha Screen Assays showed that DHTS interacts with HuR through the same binding regions as target RNAs, stabilizing HuR in a locked conformation that hampers RNA binding competitively. HuR ribonucleoprotein immunoprecipitation followed by microarray (RIP-chip) analysis showed that DHTS treatment of HeLa cells paradoxically enriched HuR binding to mRNAs with longer 3'UTR and with higher density of U/AU-rich elements, suggesting that DHTS inhibits the association of HuR to weaker target mRNAs. In vivo, DHTS potently inhibited xenograft tumor growth in a HuR-dependent model without systemic toxicity
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