Structural bioinformatics analysis of the SARS-COV-2 proteome evolution to characterize the emerging variants of the virus and to suggest possible therapeutic strategies

SARS-CoV-2 is a new coronavirus responsible for the global COVID-19 pandemic, detected in China in December 2019 and that has spread rapidly across the world. Our unit, with its specific expertise in structural bioinformatics and molecular modelling, has been involved in collaboration with epidemiology and molecular genetics groups to study SARS-CoV-2 proteome and to suggest possible molecular strategies able to inhibit virus infection. All coronaviruses, including SARS-CoV-2, evolve and adapt to the host through accumulation of mutations generated by characteristics of the virus RNA-polymerase. This work can be divided into two parts: the first part is focused onto the predictions of the potential effects of the mutations on the functions of the SARS-CoV-2 Spike glycoprotein, whereas the second part is focused at suggesting possible therapeutic strategies. In particular, I performed docking analyses to study the possible mode ad sites of interaction of inorganic polyphosphates with ACE2 and SARS-CoV-2 RNA dependent RNA polymerase (RdRp) because the molecular genetics group with whom we collaborate suggested that polyphosphates can enhance ACE2 proteasomal degradation and impair synthesis of viral RNA. In addition, I developed a pipeline to predict the most frequent sites of interaction between Spike glycoprotein and neutralizing monoclonal antibodies in order to propose therapeutic alternatives more specific and selective

Variable sequence of events during the past seven terminations in two deep-sea cores from the Southern Ocean

The relationships among internally consistent records of summer sea-surface temperature (SSST), winter sea ice (WSI), and diatomaceous stable isotopes were studied across seven terminations over the last 660 ka in sedimentary cores from ODP sites 1093 and 1094. The sequence of events at both sites indicates that SSST and WSI changes led the carbon and nitrogen isotopic changes in three Terminations (TI, TII and TVI) and followed them in the other four Terminations (TIII, TIV, TV and TVII). In both TIII and TIV, the leads and lags between the proxies were related to weak glacial mode, while in TV and TVII they were due to the influence of the mid-Pleistocene transition. We show that the sequence of events is not unique and does not follow the same pattern across terminations, implying that the processes that initiated climate change in the Southern Ocean has varied through time

La didattica della letteratura italiana del Novecento. Uno studio sul campo: i programmi e i manuali dei licei della provincia di Lucca.

La mia tesi si propone, a partire da un'analisi generale dei problemi relativi alla didattica della letteratura italiana, di presentare la storia della scuola secondaria di secondo grado e dei relativi decreti ministeriali a partire dall'Unità di Italia fino ad arrivare ai giorni nostri. Particolare attenzione è prestata al Decreto Ministeriale 211 oggi in vigore. In seguito viene fornito uno studio sui manuali di letteratura prestando un interesse maggiore ai volumi riferiti al Novecento. Segue a questa prima parte uno studio sperimentale volto a colmare, seppur nel limite del campione esaminato, la lacuna presente in Italia di un riscontro effettivo dei programmi svolti nelle scuole. Sono analizzati i programmi e i manuali relativi al XX secolo dei licei della provincia di Lucca. Iniziando da uno studio degli autori affrontati nella realtà scolastica considerata, si passa ad un confronto dei dati ottenuti con le Indicazioni nazionali del Decreto Ministeriale 211 per verificare se gli obiettivi qui proposti corrispondano ad un effettivo riscontro sul campo. Vengono inoltre analizzati all'interno del panorama novecentesco gli autori stranieri letti con più frequenza. Si fornisce infine uno studio puntale di tre autori, D'Annunzio, Montale e Fenoglio, e delle opere che di essi si riscontrano nei programmi dei licei e nei manuali, valutando in questo modo anche il peso che il libro di testo detiene nella scelta dei brani proposti in classe

Oligodendroglioma cells lack glutamine synthetase and are auxotrophic for glutamine, but do not depend on glutamine anaplerosis for growth

In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth

Feedback-controlled laser ablation for cancer treatment: comparison of On-Off and PID control strategies

: Laser ablation is a rising technique used to induce a localized temperature increment for tumor ablation. The outcomes of the therapy depend on the tissue thermal history. Monitoring devices help to assess the tissue thermal response, and their combination with a control strategy can be used to promptly address unexpected temperature changes and thus reduce unwanted thermal effects. In this application, numerical simulations can drive the selection of the laser control settings (i.e., laser power and gain parameters) and allow evaluating the thermal effects of the control strategies. In this study, the influence of different control strategies (On-Off and PID-based controls) is quantified considering the treatment time and the thermal effect on the tissue. Finite element model-based simulations were implemented to model the laser-tissue interaction, the heat-transfer, and the consequent thermal damage in liver tissue with tumor. The laser power was modulated based on the temperature feedback provided within the tumor safety margin. Results show that the chosen control strategy does not have a major influence on the extent of thermal damage but on the treatment duration; the percentage of necrosis within the tumor domain is 100% with both strategies, while the treatment duration is 630 s and 786 s for On-Off and PID, respectively. The choice of the control strategy is a trade-off between treatment duration and unwanted temperature overshoot during closed-loop laser ablation. Clinical Relevance-This work establishes that different temperature-based control of the laser ablation procedure does not have a major influence on the extent of thermal damage but on the duration of treatment

High-Level Synthesis of a Single/Multi-Band Optical and SAR Image Compression and Encryption Hardware Accelerator

Transmitting images from earth observation satellites to ground is a major challenge, and a compression/encryption stage is actually mandatory. Development of hardware accelerators is highly recommended, both to relieve the software from such demanding task, and to improve performance, aiming at quasi-real-time data processing. To this end, we discuss the design, development, deployment and test of a FPGA-based accelerator, featuring a lossless and lossy (near-lossless) compression, including the data encryption too. Its architecture is well suited for different image types, including single- and multi-band optical and SAR images and can be fully run-time configurable. Measured performance showed a throughput of 10 Msamples/s, in agreement with related state-of-the-art works, focused on lossless compression only

LOW LATENCY ON-BOARD DATA HANDLING FOR EARTH OBSERVATION SATELLITES USING OFF-THE-SHELF COMPONENTS

Satellite Earth Observation (EO) is nowadays receiving significant attention. In this regard, the latency of EO product provision to the ground segment is undoubtedly among the first key performance indicators for these systems. The European Union Horizon 2020 EO-ALERT project aims at overcoming the limitations of traditional Near Real-Time (NRT) onboard data chain architectures by moving all the critical processing tasks on the flight segment and accelerating them using high-performance commercial off-the-shelf (COTS) devices. The resulting architecture minimizes the amount of transmitted data and eliminates ground-based data processing from the EO data chain, hence achieving actual real-time product delivery in less than 5 min with optical and Synthetic Aperture Radar (SAR) data. This paper presents the performance benefits of a mixed software-hardware design of the CPU Scheduling, Compression, Encryption, and Data Handling (CS-CEDH) Subsystem responsible for data compression and encryption as well as data routing and scheduling tasks. Compared to a software-only solution, the exploited High-Level Synthesis (HLS) methodology enables 5 to 7-fold speed-up in onboard image compression and encryption tasks and 2 to 5-fold reduction in the contribution of the CS-CEDH Subsystem to the overall onboard image data chain while contributing by less than 1 s to the delivery of the alerts to the end-user

Sars-cov-2 envelope and membrane proteins: structural differences linked to virus characteristics?

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins

Ciudad de Maipú : ¿satélite o suburbio del Gran Mendoza?

Fil: Gray de Cerdán, Nelly.Fil: Peralta, Mirta Norma.Fil: Iturrioz, María Martina.Fil: Bianchi, Blanca Rosa