ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism

Background: N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing are two of the most abundant RNA modification events affecting adenosines in mammals. Both these RNA modifications determine mRNA fate and play a pivotal role in tumor development and progression. Results: Here, we show that METTL3, upregulated in glioblastoma, methylates ADAR1 mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1. We show that ADAR1 plays a cancer-promoting role independently of its deaminase activity by binding CDK2 mRNA, underlining the importance of ADARs as essential RNA-binding proteins for cell homeostasis as well as cancer progression. Additionally, we show that ADAR1 knockdown is sufficient to strongly inhibit glioblastoma growth in vivo. Conclusions: Hence, our findings underscore METTL3/ADAR1 axis as a novel crucial pathway in cancer progression that connects m6A and A-to-I editing post-transcriptional events

Studi preliminari per la redazione del piano del verde del Comune di Cecina

In ambito urbano, strumenti di pianificazione efficaci, sono fondamentali per il miglioramento della qualità ambientale delle città; per questo il piano del verde propone di affrontare la tutela della vegetazione esistente, il controllo dello stato fitosanitario e della stabilità degli alberi, il rinnovo dei popolamenti e la pianificazione dei nuovi impianti. Con la ricerca di cui si riferisce nella presente tesi, sono stati effettuati alcuni studi propedeutici per la redazione del piano del verde del Comune di Cecina (LI). Il piano del verde deve contenere una serie di strumenti tecnici e normativi, come: il censimento, il quale fornisce un quadro conoscitivo del patrimonio verde esistente e le problematiche ad esso legate; un piano generale delle manutenzioni, contenente gli interventi prevalenti sul patrimonio verde; un piano di promozione che promuove tutte le forme di partecipazione del cittadino alle attività di tutela e valorizzazione del verde; un piano di programmazione con il quale il Comune potrà affiancare alle nuove costruzioni, aree a verde adeguate ed a misura d'uomo e la redazione di un Regolamento del verde pubblico e privato che disciplina tutti gli interventi, sanzionando i casi di non rispetto delle normative. Nel lavoro che è stato svolto in questa tesi si è cercato di approfondire gli strumenti del piano: il primo passo, è stato quindi il censimento del patrimonio arboreo, iniziato dal centro città. I dati raccolti sono stati inseriti on line sul WebGIS open source Ædita, customizzato per le esigenze dei tecnici comunali. Questi ultimi, tramite username e password, possono consultare le schede delle piante censite e quelle ritenute pericolose dal rilevatore, possono predisporre i lavori da effettuare (potature, abbattimenti o indagini di stabilità) e programmare le sostituzioni. Su richiesta dei tecnici comunali sono state eseguite attraverso la metodologia V.T.A. (Visual Tree Assessment) analisi visive su varie piante e solamente su alcune poste in zone target, sono state espletate analisi strumentali con resistografo e valutazioni di carattere fitopatologico [ad es. platano affetto da cancro colorato (Ceratocystis platani) con intervento del Servizio Fitosanitario Regionale per la conferma della patologia]. Attraverso il censimento effettuato, alla proposta di un Regolamento del verde e agli altri studi preliminari (indagine pedoclimatica, demografica e urbanistica) che sono stati effettuati in questo lavoro, si auspica che il Comune possa completare la redazione del piano del verde integrandolo con il piano urbanistico, attualmente in revisione, attivando un gruppo di lavoro multidisciplinare, con specifiche competenze professionali in materia e con particolare esperienza nel campo del verde urbano

Manoscritti e edizioni

Descrizioni e analitiche illustrazioni di manoscritti delle opere di Angelo Poliziano nonch\ue9 di libri e stampe a lui appartenuti o da lui consultati e annotati nel corso del suo lungo impegno filologico e letterario

A NET ZERO ENERGY BUILDING IN ITALY: DESIGN STUDIES TO REACH THE NET ZERO ENERGY TARGET

In the framework of international actions to reduce the energy requirements and greenhouse gases emissions due to buildings, a new International Energy Agency task has been recently established in order to study Net Zero Energy Buildings (NZEBs). The commonly shared concept of NZEB, is a building whose annual balance of energy consumptions tends to zero. This concept is still too imprecise and the authors of this paper participate to the activities of SubTask B of IEA Task40 with the aim of establishing an internationally agreed understanding on NZEBs. The task is based on a common methodology for identifying and refining design approaches and tools to support industry adoption of innovative demand/supply technologies for NZEBS. This goal is pursued through detailed modeling and analysis of specific NZEB case studies. Among the specific objectives of the Sub Task B it is possible to include the analysis of redesigned studies. Redesigned studies should identify better alternative solutions for plants, building envelope or impact on the environment that significantly modify the building. To provide high quality information about the design process of a NZEB, it was decided to examine in detail the specific case study of the Leaf House (LH) located in Ancona, Italy. The studied building is fully monitored in terms of thermal environment, energy production and consumption, water use and occupancy. The purpose of this paper is to present some optionsto improve the performance of the selected building, identified by using the collected data and analyzing a detailed TRNSYS model of plant-building complex. The model has allowed detailed evaluation of the effects of some changes in the design that can improve the behavior of the Leaf House in terms of consumptions of energy resources and environmental impact of the building. The performed analysis shows that the building envelope is already very effective in terms of thermal performance, while the redesign of the thermal plants and the PV system should permit to reach a nearly net zero energy performance

THE REDESIGN OF AN ITALIAN BUILDING TO REACH NET ZERO ENERGY PERFORMANCES: A CASE STUDY OF THE SHC TASK 40 ECBCS Annex 52

In the framework of international actions to reduce the energy requirements and greenhouse gases emissions due to buildings, a new International Energy Agency task has been recently established in order to study Net Zero Energy Buildings (NZEBs). The commonly shared concept of NZEB, is a building whose annual balance of energy consumptions tends to zero. This concept is still too imprecise and the authors of this paper participate to the activities of SubTask B of IEA Task40 with the aim of establishing an internationally agreed understanding on NZEBs. The task is based on a common methodology for identifying and refining design approaches and tools to support industry adoption of innovative demand/supply technologies for NZEBS. This goal is pursued through detailed modeling and analysis of specific NZEB case studies. Among the specific objectives of the Sub Task B it is possible to include the analysis of redesigned studies. Redesigned studies should identify better alternative solutions for plants, building envelope or impact on the environment that significantly modify the building. To provide high quality information about the design process of a NZEB, it was decided to examine in detail the specific case study of the Leaf House (LH) located in Ancona, Italy. The studied building is fully monitored in terms of thermal environment, energy production and consumption, water use and occupancy. The purpose of this paper is to present some optionsto improve the performance of the selected building, identified by using the collected data and analyzing a detailed TRNSYS model of plant-building complex. The model has allowed detailed evaluation of the effects of some changes in the design that can improve the behavior of the Leaf House in terms of consumptions of energy resources and environmental impact of the building. The performed analysis shows that the building envelope is already very effective in terms of thermal performance, while the redesign of the thermal plants and the PV system should permit to reach a nearly net zero energy performance

From Experiments to a Fast Easy-to-Use Computational Methodology to Predict Human Aldehyde Oxidase Selectivity and Metabolic Reactions

Aldehyde oxidase (AOX) is a molibdo-flavoenzyme that has raised great interest in recent years, since its contribution in xenobiotic metabolism has not always been identified before clinical trials, with consequent negative effects on the fate of new potential drugs. The fundamental role of AOX in metabolizing xenobiotics is also due to the attempt of medicinal chemists to stabilize candidates toward cytochrome P450 activity, which increases the risk for new compounds to be susceptible to AOX nucleophile attack. Therefore, novel strategies to predict the potential liability of new entities toward the AOX enzyme are urgently needed to increase effectiveness, reduce costs, and prioritize experimental studies. In the present work, we present the most up-to-date computational method to predict liability toward human AOX (<i>h</i>AOX), for applications in drug design and pharmacokinetic optimization. The method was developed using a large data set of homogeneous experimental data, which is also disclosed as Supporting Information

From Experiments to a Fast Easy-to-Use Computational Methodology to Predict Human Aldehyde Oxidase Selectivity and Metabolic Reactions

Aldehyde oxidase (AOX) is a molibdo-flavoenzyme that has raised great interest in recent years, since its contribution in xenobiotic metabolism has not always been identified before clinical trials, with consequent negative effects on the fate of new potential drugs. The fundamental role of AOX in metabolizing xenobiotics is also due to the attempt of medicinal chemists to stabilize candidates toward cytochrome P450 activity, which increases the risk for new compounds to be susceptible to AOX nucleophile attack. Therefore, novel strategies to predict the potential liability of new entities toward the AOX enzyme are urgently needed to increase effectiveness, reduce costs, and prioritize experimental studies. In the present work, we present the most up-to-date computational method to predict liability toward human AOX (<i>h</i>AOX), for applications in drug design and pharmacokinetic optimization. The method was developed using a large data set of homogeneous experimental data, which is also disclosed as Supporting Information