The Inactivation Mechanism of Low Molecular Weight Phosphotyrosine-protein Phosphatase by H2O2

Low molecular weight phosphotyrosine-protein phosphatase (LMW-PTP) shares no general sequence homology with other PTPs, although it has an active site sequence motif CXXXXXR and a reaction mechanism identical to those of all PTPs. The main function of this enzyme is the down-regulation of platelet-derived growth factor and insulin receptors. Both human LMW-PTP isoenzymes are inactivated by H2O2. The enzymes are protected from inactivation by Pi, a competitive inhibitor, suggesting that the H2O2 reaction is directed to active site. Analysis of free thiols performed on the inactivated enzymes demonstrates that only two out of the eight LMW-PTP cysteines are modified. Time-course high performance liquid chromatography-electrospray mass spectrometry, together with specific radiolabeling and tryptic fingerprint analyses, enables us to demonstrate that H2O2 causes the oxidation of Cys-12 and Cys-17 to form a disulfide bond. Because both residues are localized into the active site region, this modification inactivates the enzyme. Fluorescence spectroscopy experiments suggest that the fold of the enzyme is modified during oxidation by H2O2. Because a physiological concentration of H2O2 produces enzyme inactivation and considering that the activity is restored by reduction with low molecular weight thiols, we suggest that oxidative stress conditions and other processes producing hydrogen peroxide regulate the LMW-PTP in the cell

Radar detection of pedestrian-induced vibrations on Michelangelo’s David

This paper summarizes the results of a two-day dynamic monitoring of Michelangelo's David subject to environmental loads (city traffic and pedestrian loading induced by tourists visiting the Accademia Gallery). The monitoring was carried out by a no-contact technique using an interferometric radar, whose effectiveness in measuring the resonant frequencies of structures and historic monuments has proved over the last years through numerous monitoring activities. Owing to the dynamic behavior of the measurement system (radar and tripod), an accelerometer has been installed on the radar head to filter out the movement component of the measuring instrument from the measurement of the David's displacement. Measurements were carried out in the presence and absence of visitors, to assess their influence on the dynamic behavior of the statue. A numerical model of the statue was employed to evaluate the experimental results

Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study

10openInternationalItalian coauthor/editorCorticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard’s reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples.openZecchi, Riccardo; Franceschi, Pietro; Tigli, Laura; Amidani, Davide; Catozzi, Chiara; Ricci, Francesca; Salomone, Fabrizio; Pieraccini, Giuseppe; Pioselli, Barbara; Mileo, ValentinaZecchi, R.; Franceschi, P.; Tigli, L.; Amidani, D.; Catozzi, C.; Ricci, F.; Salomone, F.; Pieraccini, G.; Pioselli, B.; Mileo, V

Investigating the potential of Cymodocea nodosa (Ucria) Ascherson as a coastal carbon sink coupling marine habitat cartographies and in situ nondestructive sampling

Seagrass meadows are major carbon sinks, trapping about 10% of the total CO2 sequestrated in the oceans. In the Mediterranean, a major focus has been made on the climax species Posidonia oceanica (L.) Delile, while other species remained little studied. In the framework of the STARECAPMED project, we thus chose to study Cymodocea nodosa (Ucria) Ascherson, a pioneer species with a rapid turnover and an expected high stocking capacity. Furthermore, the area covered by that species has been largely underestimated. In order to fill these two knowledge gaps, we first mapped all seagrass habitats within a Mediterranean bay (Calvi, Corsica, France) using side scan images, aerial photographs and ground truths. This cartography was followed by seasonal in situ density measurements and non-destructive shoot sampling (leaf cutting). Samplings were performed at different depths (5 to 23 m depth) in 6 contrasted stations (small patchy meadows to continuous beds) in order to cover all the existing facies of the bay. Elementary contents (carbon, nitrogen and stable isotope ratios) were measured in laboratory. This first work shows that C. nodosa meadows in Calvi Bay cover an area of 0.498 km2. Carbon stocks of the leaves reached 0.25 tons in winter and 2.72 tons in summer. Their nitrogen contents showed a marked seasonality with a maximum value of 0.020 mgN.m-2 in July and a minimum value of 0.005 mgN.m-2 in March. Some modifications in the trophic conditions of the water column at several stations were put in an obvious through the N stable isotopes values, mostly during the summer period. The actual underestimation of the area covered by that species in Calvi Bay has been properly mapped thanks to side scan sonar techniques revealing, together with elementary content analysis, its importance in the carbon balance of coastal areas

Key pedagogical and technological factors for effective blended learning design

This is a report by the expert pools of the EMPOWER programme established by EADTU to cover the latest trends and developments in new modes of teaching. New modes of teaching and learning create new opportunities for enhancing the quality of the learning experience in on campus programmes, reaching out to new target groups off campus and offering freely accessible courses nationally or worldwide through the internet. They enhance the quality, visibility and reputation of the institution.Co-funded by the Erasmus+ Programme of the European Unioninfo:eu-repo/semantics/publishedVersio

Surfactant-assisted distal pulmonary distribution of Budesonide revealed by mass spectrometry imaging

13openInternationalBothDirect lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lungopenZecchi, Riccardo; Franceschi, Pietro; Tigli, Laura; Pioselli, Barbara; Mileo, Valentina; Murgia, Xabier; Salomone, Fabrizio; Pieraccini, Giuseppe; Usada, Haruo; Schmidt, Augusto F; Hillman, Noah H.; Kemp, Matthew W.; Jobe, Alan H.Zecchi, R.; Franceschi, P.; Tigli, L.; Pioselli, B.; Mileo, V.; Murgia, X.; Salomone, F.; Pieraccini, G.; Usada, H.; Schmidt, A.F.; Hillman, N.H.; Kemp, M.W.; Jobe, A.H

The Imaging X-ray Polarimetry Explorer (IXPE): Technical Overview

The Imaging X-ray Polarimetry Explorer (IXPE) will expand the information space for study of cosmic sources, by adding linear polarization to the properties (time, energy, and position) observed in x-ray astronomy. Selected in 2017 January as a NASA Astrophysics Small Explorer (SMEX) mission, IXPE will be launched into an equatorial orbit in 2021. The IXPE mission will provide scientifically meaningful measurements of the x-ray polarization of a few dozen sources in the 2-8 keV band, including polarization maps of several x-ray-bright extended sources and phase-resolved polarimetry of many bright pulsating x-ray sources

Oncoplastic and reconstructive surgery in SENONETWORK Italian breast centers: lights and shadows

Highlights: • Despite the significance of oncoplastic procedure, an italian database is lacking. • Senonetwork established a multidisciplinary survey to assess their safety and efficacy. • Reconstructive outcomes were positive across low and high-volume centers. • After mastectomy, implant-based techniques are common. DTI reconstruction is advantageuos. • This contributes to the global understanding of effective strategies against breast cancer

One hundred priority questions for advancing seagrass conservation in Europe

17 pages, 2 figures.-- Open AccessSeagrass meadows provide numerous ecosystem services including biodiversity, coastal protection, and carbon sequestration. In Europe, seagrasses can be found in shallow sheltered waters along coastlines, in estuaries & lagoons, and around islands, but their distribution has declined. Factors such as poor water quality, coastal modification, mechanical damage, overfishing, land-sea interactions, climate change and disease have reduced the coverage of Europe’s seagrasses necessitating their recovery. Research, monitoring and conservation efforts on seagrass ecosystems in Europe are mostly uncoordinated and biased towards certain species and regions, resulting in inadequate delivery of critical information for their management. Here, we aim to identify the 100 priority questions, that if addressed would strongly advance seagrass monitoring, research and conservation in Europe. Using a Delphi method, researchers, practitioners, and policymakers with seagrass experience from across Europe and with diverse seagrass expertise participated in the process that involved the formulation of research questions, a voting process and an online workshop to identify the final list of the 100 questions. The final list of questions covers areas across nine themes: Biodiversity & Ecology; Ecosystem services; Blue carbon; Fishery support; Drivers, Threats, Resilience & Response; Monitoring & Assessment; Conservation & Restoration; Governance, Policy & Management; and Communication. Answering these questions will fill current knowledge gaps and place European seagrass onto a positive trajectory of recoveryThis project was initiated and carried out under the EuroSea project using funding from the United Nations Educational, Scientific and Cultural Oragnisation. Additional support was from the UK Natural Environment Research Council RESOW grant to Swansea University (NE/V016385/1). The EuroSea project is funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No 862626. Thanks to Toste Tanhua and Emma Heslop for their supporting this process. Thanks are due to FCT/MCTES for the financial support to CESAM (UIDB/50017/2020 + UIDP/50017/2020 + LA/P/0094/2020), through PT national funds. Financial support from Fundacao para a Ciencia e a Technologia was also provided through the research contract to A.I. Sousa (CEECIND/00962/2017)Peer reviewe