Bioaccumulation modelling and sensitivity analysis for discovering key players in contaminated food webs: the case study of PCBs in the Adriatic Sea

Modelling bioaccumulation processes at the food web level is the main step to analyse the effects of pollutants at the global ecosystem level. A crucial question is understanding which species play a key role in the trophic transfer of contaminants to disclose the contribution of feeding linkages and the importance of trophic dependencies in bioaccumulation dynamics. In this work we present a computational framework to model the bioaccumulation of organic chemicals in aquatic food webs, and to discover key species in polluted ecosystems. As a result, we reconstruct the first PCBs bioaccumulation model of the Adriatic food web, estimated after an extensive review of published concentration data. We define a novel index aimed to identify the key species in contaminated networks, Sensitivity Centrality, and based on sensitivity analysis. The index is computed from a dynamic ODE model parametrised from the estimated PCBs bioaccumulation model and compared with a set of established trophic indices of centrality. Results evidence the occurrence of PCBs biomagnification in the Adriatic food web, and highlight the dependence of bioaccumulation on trophic dynamics and external factors like fishing activity. We demonstrate the effectiveness of the introduced Sensitivity Centrality in identifying the set of species with the highest impact on the total contaminant flows and on the efficiency of contaminant transport within the food web

20S proteasome mediated degradation of DHFR: implications in neurodegenerative disorders

The 20S proteasome is responsible for the degradation of protein substrates implicated in the onset and progression of neurodegenerative disorders, such as a-synuclein and tau protein. Here we show that the 20S proteasome isolated from bovine brain directly hydrolyzes, in vitro, the dihydrofolate reductase (DHFR), demonstrated to be involved in the pathogenesis of neurodegenerative diseases. Furthermore, the DHFR susceptibility to proteolysis is enhanced by oxidative conditions induced by peroxynitrite, mimicking the oxidative environment typical of these disorders. The results obtained suggest that the folate metabolism may be impaired by an increased degradation of DHFR, mediated by the 20S proteasome

Simulation of operational conditions of HX-HERO in the CIRCE facility with CFD/STH coupled codes

Abstract The paper describes the application of a coupled methodology between Fluent CFD code and RELAP5 System Thermal-Hydraulic code developed at the DICI (Dipartimento di Ingegneria Civile e Industriale) of the University of Pisa. The methodology was applied specifically to the LBE-water heat exchanger HERO located inside the S100 vessel of the CIRCE facility, built at ENEA Brasimone Research Centre, to investigate the capabilities of this component. In the proposed methodology, the primary side of the HX-HERO, containing LBE, is simulated by the CFD code, while the secondary side, containing a two phase mixture of water and vapour, is reproduced by the System Thermal-Hydraulic code. During the calculation the two codes exchange, at the coupled boundaries: the bulk temperature and heat transfer coefficient of the ascending water (RELAP5 to Fluent) and the wall temperature at the water side surface of the pipes (Fluent to RELAP5). The coupling technique was tested by comparing the numerical results with the experimental data recently obtained by ENEA; the numerical results predicted well the qualitative trend of the temperature and provided an overall good prediction of the temperature also from a quantitative point of view. It is worth noticing that this good performance remained reliable for all the cases simulated, proving the general applicability of the methodology

Coupled system thermal Hydraulics/CFD models: General guidelines and applications to heavy liquid metals

This work aims to review the general guidelines to be adopted to perform coupled System Thermal Hydraulics (STH)/CFD calculations. The coupled analysis is often required when complex phenomena characterized by different characteristic time and length scales are investigated. Indeed, by STH/CFD coupling the main drawbacks of both stand-alone codes are overcome, reducing the computational cost and providing more realistic solutions. A review of several works available in literature and involving different coupling approaches, codes, time-advancing schemes and application fields is given. Besides STH/CFD coupling techniques, spatial domains and numerical schemes are analysed in detail. A brief description of applications to heavy liquid metal systems is also reported; lessons drawn in the frame of these and other works are then considered in order to develop a set of good practice guidelines for coupled STH/CFD applications

Three-dimensional superimposition for patients with facial palsy: an innovative method for assessing the success of facial reanimation procedures

Facial palsy is a severe condition that may be ameliorated by facial reanimation, but there is no consensus about how to judge its success. In this study we aimed to test a new method for assessing facial movements based on 3-dimensional analysis of the facial surfaces. Eleven patients aged between 42 and 77 years who had recently been affected by facial palsy (onset between 6 and 18 months) were treated by an operation based on triple innervation: the masseteric to temporofacial nerve branch, 30% of the hypoglossal fibres to the cervicofacial nerve branch, and the contralateral facial nerve through two cross-face sural nerve grafts. Each patient had five stereophotogrammetric scans: at rest, smiling on the healthy side (facial stimulus), biting (masseteric stimulus), moving the tongue (hypoglossal stimulus), and corner-of-the-mouth smile (Mona Lisa). Each scan was superimposed onto the facial model of the "rest" position, and the point-to-point root mean square (RMS) value was automatically calculated on both the paralysed and the healthy side, together with an index of asymmetry. One-way and two-way ANOVA tests, respectively, were applied to verify the significance of possible differences in the RMS and asymmetry index according to the type of stimulus (p = 0.0329) and side (p < 0.0001). RMS differed significantly according to side between the facial stimulus and the masseteric one on the paralysed side (p = 0.0316). Facial stimulus evoked the most asymmetrical movement, whereas the masseteric produced the most symmetrical expression. The method can be used for assessing facial movements after facial reanimation

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

12-months prospective Pentraxin-3 and metabolomic evaluation in multiple sclerosis patients treated with glatiramer acetate

Background: Pentraxin-3 (PTX-3) is involved in acute immunological responses and it is a pro-inflammatory protein and a novel biomarker of inflammatory diseases. It is demonstrated that PTX-3 is higher in cerebrospinal fluid (CSF) of aggressive Multiple Sclerosis (MS). Metabolomics, the identification of small endogenous molecules, offers a molecular profile of MS. Glatiramer acetate (GA) is a widely used treatment for (MS) but its mechanism of action is not completely defined. The aim of our study is to analyze PTX-3 and metabolomic profile in MS patients compared to controls and to investigate the effect of GA on PXT-3 and metabolic molecules during treatment in responder and not responder MS patients. Methods: 28 unrelated MS patients and 27 age-and sex-matched controls were recruited. In serum, PTX-3 levels were measured by ELISA and Metabolomic panel was evaluated trough Nuclear Magnetic Resonance (NMR). According to clinical practice patients started GA treatment; PTX-3 and metabolomic identification were performed before and during treatment. Responders to treatment were identified if no evidence of instrumental, clinical relapses and disability progression (NEDA) occurred during follow up. Results: Serum PTX-3 levels were higher in MS patients compared to matched controls (7,85 ± 2,19 vs 6,20 ± 1,63 ng/ml) (p = 0,03); metabolomic evaluation shows higher levels of lactate and lower levels of valine, tyrosine and tryptophan in MS patients compared to controls. During therapy, PTX-3 levels have been reduced statistically significant (p = 0,001) at six months and one year of treatment. After one year, of the twenty patients that completed the study, 55% were considered fully responders to treatment; in these patients the mean reduction of PTX-3 at one year was higher respect to not responders (−3,82 ± 1,24 ng/ml vs −2,32 ± 1,03 ng/ml p = 0,02) and we observed a higher reduction of lactate, tyrosine and hypoxanthine and an increase of hydroxyproline and ADP as well as of three oxidative phosphorylation markers, citrulline, ornithine and tryptophan approaching the metabolic profile of healthy subjects. Discussion and conclusions: We demonstrated a metabolomic imbalance with mitochondrial dysfunction detected by higher levels of lactate and lower levels of tryptophan, tyrosine and valine in MS patients compared to healthy controls. The reduction of PTX-3 levels and the restoring of mitochondrial function, reducing oxidative stress by GA, allows to identify responder patients. Further and larger studies are needed to understand the predictive role of PTX-3 and metabolomic pattern in the identification of responder patients to GA

Cu,Zn Superoxide Dismutases from Tetrahymena thermophila: Molecular Evolution and Gene Expression of the First Line of Antioxidant Defenses

In the present study, we describe the molecular and functional characterization of two Cu,Zn superoxide dismutase (SOD) genes, named tt-sod1a and tt-sod1b from Tetrahymena thermophila, a free-living ciliated protozoan widely used as model organism in biological research. The cDNAs and the putative amino acid sequences were compared with Cu,Zn SODs from other Alveolata. The primary sequences of T. thermophila Cu,Zn SODs are unusually long if compared to orthologous proteins, but the catalytically important residues are almost fully conserved. Both phylogenetic and preliminary homology modeling analyses provide some indications about the evolutionary relationships between the Cu,Zn SODs of Tetrahymena and the Alveolata orthologous enzymes. Copper-dependent regulation of Cu,Zn SODs expression was investigated by measuring mRNA accumulation and enzyme activity in response to chronic exposure to non-toxic doses of the metal. Our in silico analyses of the tt-sod1a and tt-sod1b promoter regions revealed putative consensus sequences similar to half Antioxidant Responsive Elements (hARE), suggesting that the transcription of these genes directly depends on ROS formation. These data emphasize the importance of complex metal regulation of tt-sod1a and tt-sod1b activation, as components of an efficient detoxification pathway allowing the survival of T. thermophila in continued, elevated presence of metals in the environment

Fast high-quality MRI protocol of the lumbar spine with deep learning-based algorithm: an image quality and scanning time comparison with standard protocol

Objective: The objective of this study is to prospectively compare quantitative and subjective image quality, scanning time, and diagnostic confidence between a new deep learning-based reconstruction(DLR) algorithm and standard MRI protocol of lumbar spine. Materials and methods: Eighty healthy volunteers underwent 1.5T MRI examination of lumbar spine from September 2021 to May 2023. Protocol acquisition comprised sagittal T1- and T2-weighted fast spin echo and short-tau inversion recovery images and axial multislices T2-weighted fast spin echo images. All sequences were acquired with both DLR algorithm and standard protocols. Two radiologists, blinded to the reconstruction technique, performed quantitative and qualitative image quality analysis in consensus reading; diagnostic confidence was also assessed. Quantitative image quality analysis was assessed by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Qualitative image quality analysis and diagnostic confidence were assessed with a five-point Likert scale. Scanning times were also compared. Results: DLR SNR was higher in all sequences (all p&lt;0.001). CNR of the DLR was superior to conventional dataset only for axial and sagittal T2-weighted fast spin echo images (p&lt;0.001). Qualitative analysis showed DLR had higher overall quality in all sequences (all p&lt;0.001), with an inter-rater agreement of 0.83 (0.78-0.86). DLR total protocol scanning time was lower compared to standard protocol (6:26 vs 12:59 min, p&lt;0.001). Diagnostic confidence for DLR algorithm was not inferior to standard protocol. Conclusion: DLR applied to 1.5T MRI is a feasible method for lumbar spine imaging providing morphologic sequences with higher image quality and similar diagnostic confidence compared with standard protocol, enabling a remarkable time saving (up to 50%)