Ottaviano Volpelli e il recupero di un'epigrafe suasana finita a San Leo

Il convegno per i venti anni di scavi nella citt\ue0 romana di Suasa offre l\u2019occasione all\u2019a. per appuntare l\u2019attenzione su Ottaviano Volpelli, un personaggio vissuto nel \u2018500 al servizio dei Della Rovere di Urbino, rimasto fin qui totalmente ignorato. Eppure, raccogliendo indizi sparsi in testimonianze di vario genere, peraltro notevoli per valore, si scopre egli \u2013 laureato in diritto e dotato di un\u2019ampia cultura - fu il primo a scoprire la citt\ue0 romana, identificandone con esattezza il sito grazie a scavi compiutevi di persona, che gli permisero di recuperare statue, iscrizioni con il nome di Suasa ed altri reperti di vario genere. Si ricostruiscono cos\uec in parte attivit\ue0 e movimenti di quest\u2019uomo, nato a Sant\u2019Angelo in Vado, residente a San Leo e in possesso di terre a Castelleone di Suasa. Emerge in particolare il suo interesse per le antichit\ue0 che lo porta ad allestire una raccolta di reperti romani nella propria abitazione di San Leo, dove confluiscono tra l\u2019altro epigrafi provenienti da Suasa e da Pesaro, di cui \u2013 essendo state poi trasferite verso la met\ue0 del \u2018700 nel Lapidario del Palazzo Ducale di Urbino - si ignoravano fin qui pressoch\ue9 del tutto queste vicende. Si chiarisce cos\uec la storia di una importante epigrafe (CIL XI 6481) - in cui si parla di un teatro, di magistrati ed altre istituzioni cittadine \u2013 a cui la letteratura scientifica ha fin qui faticato a trovare una giustificazione storica a San Leo (dove la pietra si trovava, ma dove non esistono tracce di civilt\ue0 romana), potendosi ora ricostruirne il percorso da Suasa a San Leo, portatavi da Ottaviano Volpelli

Le trib\uf9 romane nella regio V e nella parte adriatica della regio VI

Poich\ue9 vi \ue8 uno stretto rapporto tra le vicende storiche del territorio (conquista da parte di Roma, fondazione delle colonie, creazione dei municipi, alternarsi della condizione giuridica del municipio a quella della colonia, e viceversa) e la registrazione degli abitanti in determinati distretti elettorali (tribus), l\u2019argomento viene qui affrontato \u2013 nell\u2019ambito di uno specifico convegno dedicato al tema delle trib\uf9 romane \u2013 in riferimento alle comunit\ue0 antiche del territorio marchigiano. E ci\uf2 tenendo conto del fatto che mentre sulla parte settentrionale di esso (Umbria et ager Gallicus) esiste uno studio abbastanza recente (G. Forni 1982), per quella meridionale (Picenum) l\u2019unico lavoro risale alla fine dell\u2019Ottocento (J.W. Kubitschek 1889), mentre lo sviluppo della riflessione storiografica e il moltiplicarsi delle acquisizioni epigrafiche sono nel frattempo a modificare il quadro delle nostre conoscenze. Il lavoro procede dunque ad esaminare le varie e molteplici attestazioni di trib\uf9 romane nel territorio in esame in rapporto alle vicende storiche che nello stesso hanno avuto via via luogo. Si affrontano cos\uec questioni complesse e delicate, relative alla politica perseguita da Roma nella gestione dei territori conquistati, come \ue8 il caso \u2013 per esempio \u2013 dell\u2019ager Gallicus, su cui ferve da tempo un dibattito intenso

A new procedure to analyze RNA non-branching structures

RNA structure prediction and structural motifs analysis are challenging tasks in the investigation of RNA function. We propose a novel procedure to detect structural motifs shared between two RNAs (a reference and a target). In particular, we developed two core modules: (i) nbRSSP_extractor, to assign a unique structure to the reference RNA encoded by a set of non-branching structures; (ii) SSD_finder, to detect structural motifs that the target RNA shares with the reference, by means of a new score function that rewards the relative distance of the target non-branching structures compared to the reference ones. We integrated these algorithms with already existing software to reach a coherent pipeline able to perform the following two main tasks: prediction of RNA structures (integration of RNALfold and nbRSSP_extractor) and search for chains of matches (integration of Structator and SSD_finder)

SAveRUNNER: an R-based tool for drug repurposing

Background: Currently, no proven effective drugs for the novel coronavirus disease COVID-19 exist and despite widespread vaccination campaigns, we are far short from herd immunity. The number of people who are still vulnerable to the virus is too high to hamper new outbreaks, leading a compelling need to find new therapeutic options devoted to combat SARS-CoV-2 infection. Drug repurposing represents an effective drug discovery strategy from existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. Results: We developed a network-based tool for drug repurposing provided as a freely available R-code, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), with the aim to offer a promising framework to efficiently detect putative novel indications for currently marketed drugs against diseases of interest. SAveRUNNER predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-associated proteins in the human interactome through the computation of a novel network-based similarity measure, which prioritizes associations between drugs and diseases located in the same network neighborhoods. Conclusions: The algorithm was successfully applied to predict off-label drugs to be repositioned against the new human coronavirus (2019-nCoV/SARS-CoV-2), and it achieved a high accuracy in the identification of well-known drug indications, thus revealing itself as a powerful tool to rapidly detect potential novel medical indications for various drugs that are worth of further investigation. SAveRUNNER source code is freely available at https://github.com/giuliafiscon/SAveRUNNER.git, along with a comprehensive user guide

SPINNAKER: an R-based tool to highlight key RNA interactions in complex biological networks

Background: Recently, we developed a mathematical model for identifying putative competing endogenous RNA (ceRNA) interactions. This methodology has aroused a broad acknowledgment within the scientific community thanks to the encouraging results achieved when applied to breast invasive carcinoma, leading to the identification of PVT1, a long non-coding RNA functioning as ceRNA for the miR-200 family. The main shortcoming of the model is that it is no freely available and implemented in MATLAB®, a proprietary programming platform requiring a paid license for installing, operating, manipulating, and running the software. Results: Breaking through these model limitations demands to distribute it in an open-source, freely accessible environment, such as R, designed for an ordinary audience of users that are not able to afford a proprietary solution. Here, we present SPINNAKER (SPongeINteractionNetworkmAKER), the open-source version of our widely established mathematical model for predicting ceRNAs crosstalk, that is released as an exhaustive collection of R functions. SPINNAKER has been even designed for providing many additional features that facilitate its usability, make it more efficient in terms of further implementation and extension, and less intense in terms of computational execution time. Conclusions: SPINNAKER source code is freely available at https://github.com/sportingCode/SPINNAKER.git together with a thoroughgoing PPT-based guideline. In order to help users get the key points more conveniently, also a practical R-styled plain-text guideline is provided. Finally, a short movie is available to help the user to set the own directory, properly

Forced into shape: Mechanical forces in Drosophila development and homeostasis

Mechanical forces play a central role in shaping tissues during development and maintaining epithelial integrity in homeostasis. In this review, we discuss the roles of mechanical forces in Drosophila development and homeostasis, starting from the interplay of mechanics with cell growth and division. We then discuss several examples of morphogenetic processes where complex 3D structures are shaped by mechanical forces, followed by a closer look at patterning processes. We also review the role of forces in homeostatic processes, including cell elimination and wound healing. Finally, we look at the interplay of mechanics and developmental robustness and discuss open questions in the field, as well as novel approaches that will help tackle them in the future

Donor-strand exchange in chaperone-assisted pilus assembly revealed in atomic detail by molecular dynamics

Adhesive multi-subunit fibres are assembled on the surface of many pathogenic bacteria via the chaperone-usher pathway. In the periplasm, a chaperone donates a β-strand to a pilus subunit to complement its incomplete immunoglobulin-like fold. At the outer membrane, this is replaced with a β-strand formed from the N-terminal extension (Nte) of an incoming pilus subunit by a donorstrand exchange (DSE) mechanism. This reaction has previously been shown to proceed via a concerted mechanism, in which the Nte interacts with the chaperone:subunit complex before the chaperone has been displaced, forming a ternary intermediate. Thereafter, the pilus and chaperone β-strands have been postulated to undergo a strand swap by a ‘zip-in-zip-out’ mechanism, whereby the chaperone strand zips out, residue by residue, as the Nte simultaneously zips in. Here, molecular dynamics simulations have been used to probe the DSE mechanism during formation of the Salmonella enterica Saf pilus at an atomic level, allowing the direct investigation of the zip-inzip- out hypothesis. The simulations provide an explanation of how the incoming Nte is able to dock and initiate DSE due to inherent dynamic fluctuations within the chaperone:subunit complex. The chaperone donor-strand is shown to unbind from the pilus subunit residue by residue, in direct support of the zip-in-zip-out hypothesis. In addition, an interaction of a residue towards the Nterminus of the Nte with a specific binding pocket (P*) on the adjacent pilus subunit is shown to stabilise the DSE product against unbinding, which also proceeds by a zippering mechanism. Together, the study provides an in-depth picture of DSE, including the first insights into the molecular events occurring during the zip-in-zip-out mechanism

Effect of dietary turmeric powder (Curcuma longa L.) on cooked pig meat quality

The study was carried out on raw meat samples derived from pigs fed with a control diet and a diet supplemented with daily 4.5 g of turmeric powder per pig. After slaughter raw meat was stored for 7 days at 4°C. At Day 0 and Day 7 samples were cooked in a preheated oven at 163°C to the internal temperature of 71°C. Colour parameters, Warner Bratzler shear force, TBARS and antioxidant capacity (ABTS, DPPH and FRAP) were determined at Day 0 and Day 7. Dietary turmeric powder induced an increase in cooked meat of L* value (P < 0.001) and reductions in a*, b* indexes and in C* value (P < 0.01, P < 0.001 and P < 0.001, respectively). Colour modifications in cooked meat were correlated with colour parameters of raw samples. The Curcuma longa powder dietary supplementation did not affect lipid oxidation, Warner Bratzler shear force and antioxidant capacity of cooked meat (P > 0.05)

Stress evaluation in hares (Lepus europaeus Pallas) captured for traslocation

With the aim to evaluate the capturing techniques some haematic and physiological parameters were studied to discrim- inate stressed hares from non stressed hares. A total of 66 wild hares (experimental group) were sampled in 14 different non-hunting areas, where hares are usually captured for later release in low-density areas. In the same season a total of 30 hares (about 1 year old), reared in cages and thus showing a reduced fear of man, were sampled (control group). In each area the hares were captured by cours- ing with 3-4 dogs (greyhounds or lurches). The dogs were released by the different hunter teams to find and drive into trammel nets any hare that was seen running. After capture, the hares remained inside darkened, wooden capture-boxes for a variable period of time before blood drawing. For blood sample collection all the hares were physically restrained and their eyes immediately covered. Blood, always collected within 1-2 minutes, was drawn from the auricular vein. Blood samples (plasma) were analysed for glucose, AST, ALT, CPK and cortisol concentrations. Body temperature, heart and respiratory rate, sex, and age were evaluated in each hare. The effect of origin, sex and age on haematic and physiolog- ical parameters was analysed by ANOVA. Every measured parameter of the hares bearing to the capture group or the control group (reared) was then subjected to stepwise and to discriminant analysis, in order to select the groups of stressed (discriminated by the controls) and non-stressed hares. CPK, AST and glucose were found to be the best parameters for distinguishing stressed from non-stressed hares. The intensive exercise suffered by the wild hares induced a depletion of energetic reserves, so that most of the captured hares showed lower glucose and higher CPK activity in the plasma, probably due to muscle damage (P< 0.05). After reclassi- fying the hares in the two groups of stressed and non stressed hares, the reference values (means ± SE) resulted as fol- lows: estimated non-stressed hares, glucose 234 ± 9 .4 mg/dl, AST 112 ± 22.2 U/l, CPK 1334 ± 734 U/l; estimated stressed hares, glucose 128 ± 7 mg/dl, AST 164 ± 13 U/l, CPK 4658 ± 454 U/l. These three cheap and quickly analysable analytes can be useful to the game manager in detecting stressed and non stressed hares, in order to improve the capturing techniques by the evaluation of the following relationship: (number of stressed hares + number of the dead hares during the capture)/number of total captured hares

Recognition mechanism of p63 by the E3 ligase Itch Novel strategy in the study and inhibition of this interaction.

The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer’s or Huntington’s diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly 13C-15N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534–551 residue of p63, encompassing the PP xY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PP xY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase