38 research outputs found
Deconvolution of bioactive molecules: label-free functional proteomics to investigate the cytotoxic compound LAM20 target(s) profile
No full textDeconvolution of bioactive molecules: label-free functional proteomics to investigate the cytotoxic compound LAM20 target(s) profile
Territorial capital as a source of firm competitive advantage: evidence from the North and South of Italy
No full textThis paper investigates how territorial capital, defined as a ‘mix‘ of tangible and intangible local resources accumulated over time across different territories, becomes a source of competitive advantage for firms. The study draws upon semi-structured interviews with firms' owner-managers operating in the North and South of Italy and shows how local resources generate firms' costs and differentiation advantages through acting as territorial externalities or becoming an essential core asset to the firm. Results demonstrate how local resources are highly interconnected, making territorial capital unique in each place and not easily imitable, which ensures long term competitive advantages for those firms that benefit from its endowment. A mix of advanced local resources developed through long term investment is shown to be more valuable for firms than inherited resources, provided by ‘God’ or ‘ancestors’. Using the concept of territorial capital in this manner provides insights into understanding sources of firm competitiveness related to location and the persistence of territorial economic disparities
The socio-economic value of scientific publications: The case of Earth Observation satellites
No full textThis paper provides a conceptual framework to estimate the socio-economic benefits of new knowledge generated within research infrastructures from the scientific community's perspective. We use Earth Observation (EO) satellites as a case study. Constructing, operating, and exploiting cutting-edge EO infrastructures is generating a vast amount of knowledge ultimately embodied in scientific publications. Using bibliometric and machine learning techniques, we analyse 1,235 publications in 1998–2018 related to Cosmo Skymed, the EO satellites constellation of the Italian Space Agency. Thanks to these satellites, 2,377 authors from 160 institutions and 68 countries worldwide have contributed to various subjects in several scientific fields. By using the marginal social value method in a cost-benefit analysis perspective, we conservatively estimate the value of such publications, including their marginal cost and value of citations. This original and straightforward approach can be used to estimate the socio-economic value of scientific publications produced within any research infrastructure, including universities, in any field of study
The socio-economic value of scientific publications: The case of Earth Observation satellites
No full textThis paper provides a conceptual framework to estimate the socio-economic benefits of new knowledge generated within research infrastructures from the scientific community's perspective. We use Earth Observation (EO) satellites as a case study. Constructing, operating, and exploiting cutting-edge EO infrastructures is generating a vast amount of knowledge ultimately embodied in scientific publications. Using bibliometric and machine learning techniques, we analyse 1,235 publications in 1998–2018 related to Cosmo Skymed, the EO satellites constellation of the Italian Space Agency. Thanks to these satellites, 2,377 authors from 160 institutions and 68 countries worldwide have contributed to various subjects in several scientific fields. By using the marginal social value method in a cost-benefit analysis perspective, we conservatively estimate the value of such publications, including their marginal cost and value of citations. This original and straightforward approach can be used to estimate the socio-economic value of scientific publications produced within any research infrastructure, including universities, in any field of study
Roma, Piazzale Ipponio, scavi delle Metropolitana C per la stazione Amba Aradam-Ipponio. Ceramiche fini, lucerne e anfore dalla dismissione di un condotto fognario dall’ex caserma adrianea
No full textThis paper focuses on the wares (fine wares, lamps and amphora) recovered from a sewer at the military complex discovered in Rome during the excavations for the metro Line C at the Amba Aradam station. The good state of preservation of the ce-ramics from this deposit suggests they were likely in use when they were dumped into the channel of the sewer. Accordingly, this assemblage offers an essential opportunity for a better understanding of the material culture circulating within Rome in the last decades of the 3rd century, which is a phase that is underrepresented archaeologically
A functional proteomics-based platform to disclose small molecules cellular targets
No full textEsposizione risultati di chimica proteomic
PROTEOMICS-AIDED INSIGHT TO DISCLOSE NATURAL PRODUCTS CELLULAR TARGETS
No full textActually, the identification of the potential primary cellular targets of bioactive natural products (NPs), along
with their off-targets, is an important concern. Currently, affinity purification targets identification methods
based on mass spectrometry, called AP-MS, are the most reliable ones [1]. However, they are limited by the
NPs chemical modification: to overcome this constraint, a simple, universally applicable approach based
on the direct binding of an unmodified compound to its targets, termed DARTS (drug affinity responsive
target stability), can be performed. DARTS takes advantage of a reduction in the protease susceptibility
of the target protein upon drug binding. This phenomenon allows the drug target(s) to be revealed by a
gel-based approach, useful for protein bands visualization showing different protease accessibility, and
proteomics identification [2]. Then, LiP-MRM approach couples limited proteolysis (LiP) with targeted
mass spectrometric tools, exploiting the sensitivity and background filtering capabilities of multiple reaction
monitoring (MRM) experiments [3]. As previously described for DARTS, LiP involves the use of a broadspecificity protease, such as subtilisin, under controlled conditions such that primary cleavage sites are
dictated by the structural conformation of the protein which can be modified by drug interaction. Altered
LiP patterns can be measured directly in a complex proteome matrix pointing out which protein regions are
masked by NPs. Several examples will be discussed
Un tratto di acquedotto repubblicano rinvenuto negli scavi Metro C di Piazza Celimontana, Roma
No full textNel mese di dicembre 2016 si sono concluse le indagini archeologiche svolte nei giardini di piazza Celimontana sul Celio in occasione dei lavori della tratta T3 della linea C della Metropolitana di Roma, che collega S. Giovanni in Laterano al Colosseo. Lo scavo, preliminare alle opere civili, è stato eseguito all’interno di un pozzo circolare di aerazione di circa 32 metri di diametro, esteso su una superficie di oltre 800 metri quadri, ubicato nell’angolo nord-orientale della piazza. Nell'ambito delle ricerche è stato messo in luce un tratto di acquedotto sotterraneo medio repubblicano, interamente realizzato in opera quadrata che, con andamento est-ovest, attraversa l’asse centrale del Pozzo e prosegue oltre le paratie di cemento che delimitano l’area d’indagin
Carbamoyl-phosphate synthase 1 as a novel target of phomoxanthone a, a bioactive fungal metabolite
No full textPhomoxanthone A, a bioactive xanthone dimer isolated from the endophytic fungus Phomopsis sp., is a mitochondrial toxin weakening cellular respiration and electron transport chain activity by a fast breakup of the mitochondrial assembly. Here, a multi-disciplinary strategy has been developed and applied for identifying phomoxanthone A target(s) to fully address its mechanism of action, based on drug affinity response target stability and targeted limited proteolysis. Both approaches point to the identification of carbamoyl-phosphate synthase 1 as a major phomoxanthone A target in mitochondria cell lysates, giving also detailed insights into the ligand/target interaction sites by molecular docking and assessing an interesting phomoxanthone A stimulating activity on carbamoyl-phosphate synthase 1. Thus, phomoxanthone A can be regarded as an inspiring molecule for the development of new leads in counteracting hyperammonemia states
Analysis of Hsp90 allosteric modulators interactome reveals a potential dual action mode involving mitochondrial MDH2
No full textHsp90 (i.e., Heat shock protein 90) is a well-established therapeutic target for several diseases, ranging from misfolding-related disfunctions to cancer. In this framework, we have developed in recent years a family of benzofuran compounds that act as Hsp90 allosteric modulators. Such molecules can interfere with the stability of some relevant Hsp90 client oncoproteins, showing a low μM cytotoxic activity in vitro in cancer cell lines. Here we identify the target profile of these chemical probes by means of chemical proteomics, which established MDH2 (mitochondrial malate dehydrogenase) as an additional relevant cellular target that might help elucidate the molecular mechanism of their citotoxicity. Western blotting, DARTS (i.e., Drug Affinity Responsive Target Stability) and enzymatic assays data confirmed a dose-dependent interaction of MDH2 with several members of the benzofuran Hsp90 modulators family and a computational model allowed to interpret the observed interactions
