1,700 research outputs found
PLEIOTROPIC PHENOTYPE OF PSEUDOMONAS AERUGINOSA MUTANTS DEFECTIVE IN GLUCOSE UPTAKE
Pseudomonas aeruginosa è un patogeno opportunista che provoca una vasta gamma di infezioni nell’uomo. È noto che l’incidenza delle infezioni da P. aeruginosa è maggiore in persone che presentano elevati livelli di glucosio nel sangue, a causa della capacità del batterio di utilizzare il glucosio in eccesso come nutriente per la crescita. Pertanto, bloccare l’attività di proteine coinvolte nel trasporto o nell’utilizzazione del glucosio da parte del batterio potrebbe essere una buona strategia per lo sviluppo di farmaci anti-pseudomonas.
Per valutare questa ipotesi, abbiamo costruito una serie di mutanti singoli e multipli difettivi nel trasporto del glucosio nel ceppo PAO1 di P. aeruginosa e li abbiamo analizzati per fenotipi correlati alla virulenza in saggi in vitro e in vivo, in due differenti modelli di infezione. In particolare, sono stati deleti i geni codificanti per i trasportatori della membrana interna Glt, GntP e Kgut, che mediano l’ingresso del glucosio e dei suoi derivati ossidati gluconato e 2-ketogluconato. Un triplo mutante privo dei suddetti trasportatori si è rivelato incapace di crescere su glucosio come unica fonte di carbonio (mutante GUN, Glucose Uptake Null).
Più di 500 geni, che controllano sia funzioni metaboliche che la virulenza, sono espressi in modo differenziale nel mutante GUN rispetto al ceppo parentale. Coerentemente con i dati dell’analisi trascrittomica, i saggi di virulenza in vitro hanno mostrato che il mutante GUN si comporta diversamente dal ceppo parentale, avendo una ridotta capacità di formare biofilm e una maggiore secrezione di proteasi, piocianina e pioverdina. Inoltre, questo mutante ha una produzione alterata delle molecole segnale che attivano il sistema del quorum sensing. È interessante notare che il profilo trascrizionale e la maggior parte dei tratti fenotipici analizzati differiscono tra il mutante GUN e il ceppo parentale indipendentemente dalla presenza del glucosio, suggerendo che uno (o più) dei trasportatori deleti abbia una funzione addizionale non correlata al trasporto del glucosio.
Infine, alcuni mutanti hanno mostrato un diverso grado di virulenza in saggi di infezione negli ospiti modello Caenorhabditis elegans e Galleria mellonella. In particolare, mentre in C. elegans la virulenza dei mutanti è risultata simile a quella del ceppo parentale PAO1, i mutanti deleti del gene kguT, che codifica per il trasportatore del 2-ketogluconato, sono meno virulenti di PAO1 in G. mellonella. L’attenuazione è particolarmente significativa per il doppio mutante ΔgntP ΔkguT e per il mutante GUN. Questo risultato suggerisce che l’efficacia antibatterica di composti che bloccano l’utilizzo del glucosio da parte di P. aeruginosa potrebbe presumibilmente variare a seconda della capacità del patogeno di adattarsi allo specifico contesto nutrizionale dell’ospite infettato. Una maggiore conoscenza delle interazioni metaboliche che avvengono tra patogeno ed ospite nel sito d’infezione diventa quindi sempre più necessaria per poter sviluppare terapie antibatteriche efficaci.Pseudomonas aeruginosa is an opportunistic pathogen causing a wide range of infections in humans. Pathologies leading to hyperglycaemia have been associated with augmented risk of developing serious P. aeruginosa infections due to the ability of the bacterium to utilize glucose as carbon source for the growth. Therefore, preventing the import of glucose might be a good strategy to develop anti-pseudomonas drugs.
To address this hypothesis, a collection of single and multiple glucose uptake defective mutants was generated in P. aeruginosa PAO1 and tested for virulence-related phenotypes in in vitro assays and in vivo, in two different infection models. In particular, we engineered mutants in genes encoding inner membrane (IM) proteins involved in the internalization of glucose and its oxidized derivatives gluconate and 2-ketogluconate, i.e. the Glt, GntP and KguT transporters. A triple mutant lacking these transporters was demonstrated to be completely unable to grow on glucose as sole carbon source (Glucose Uptake Null mutant, GUN).
The transcriptomic analysis revealed a strong divergence in the GUN transcriptional profile relative to the parental strain, with more than 500 differentially expressed genes, controlling both metabolic functions and virulence traits. Consistent with the transcriptomic data, the GUN mutant showed a pleiotropic phenotype in the in vitro assays, with a reduction in biofilm formation and an increased secretion of proteases, pyocyanin and pyoverdine. Furthermore, the production of quorum sensing signal molecules was altered in this mutant. Interestingly, the gene expression profile and most phenotypic traits differ between GUN and the parental strain irrespective of the presence of glucose, suggesting a possible additional role for the deleted transporter(s).
Finally, the in vivo assays demonstrated that while the virulence of all mutants in the Caenorhabditis elegans infection model was essentially comparable to that of the wild type strain, all mutants lacking kguT (i.e. the 2-ketogluconate transporter gene) and especially the double ΔgntP ΔkguT and GUN mutants, were attenuated in the Galleria mellonella model. This suggests that targeting glucose metabolism with specific drugs may alter P. aeruginosa pathogenicity depending on the ability of this pathogen to adapt to the specific nutritional context encountered at the site of infection. Therefore, a deeper knowledge of host-pathogen metabolic transactions is pivotal to develop effective antibacterial strategies based on hampering bacterial metabolic functions
TUTELA DEL LAVORO E LIBERTA' D'IMPRESA NEI PROCESSI DI ESTERNALIZZAZIONE
L’elaborato analizza le conseguenze lavoristiche della successione fra imprenditori, muovendo da una ricognizione delle varie tipologie di esternalizzazione con le relative esigenze e principali criticità.
L’indagine si concentra in primo luogo sul trasferimento d’azienda, esaminando la normativa e la giurisprudenza europee per passare poi alla disciplina di diritto interno, alle procedure sindacali e a uno specifico focus sul trasferimento delle aziende in crisi.
Successivamente l’autore si sofferma sull’appalto, prendendone in particolare considerazione gli indici di genuinità, i criteri di distinzione dalla somministrazione illecita di manodopera e la tutela delle maestranze in caso di avvicendamento fra imprese.
Da ultimo, la ricerca approfondisce le c.d. “clausole sociali”, sia di prima che di seconda generazione, valutandone la compatibilità con il diritto eurounitario e con la costituzione nonché riflettendo sui possibili rimedi in caso di loro violazione.The author analyzes the labour consequences of the succession between entrepreneurs, starting from a recognition of the various types of outsourcing with the related needs and main critical issues.
The survey focuses primarily on the transfer of businesses, examining European legislation and case-law and then moving on to internal legislation, trade union procedures and a specific focus on the transfer of companies in crisis.
The author then dwells on the contract, taking into account in particular the indications of authenticity, the criteria of distinction from the illicit administration of labour and the protection of workers in the event of turnover between companies.
Finally, the research deepens the "social clauses", both first and second generation, assessing their compatibility with European law and with the constitution and reflecting on possible remedies in case of their violation
Ultra Low Carbon Vehicles: New Parameters for Automotive Design
As the influence of vehicle emissions on our environment has become better understood, the UK government has recently placed urgent emphasis on the implementation of low carbon
technologies in the automotive industry through: the UK Low Carbon Industrial Strategy. The overall objective is to offer big incentives to consumers and support for the development of infrastructure and engineering solutions. This scheme however does not consider how the development of functional and experiential user value might drive consumer demand, contributing to the adoption of low carbon vehicles (LCVs) in the mass market.
With the emergence of the North East of England as the UK’s first specialised region for the development of ultra-low carbon vehicles (ULCVs), ONE North East, as a development agency for the region's economic and business development, and Northumbria University Ideas-lab have supported a project to facilitate innovation through the collaboration of technology, research and development (R&D) and business. The High Value Low Carbon (HVLC) project aims to envisage
new user value made possible by the integration of low carbon vehicle platforms with new process and network technologies. The HVLC consortium represents vehicle manufacturers and their suppliers as well as technology based companies and through an ongoing process of design concept generation the project offers a hub for innovation led enterprise.
Whilst new technological developments in areas such as power generation, nano materials, hydrogen fuel cells, printed electronics and networked communications will all impact on future automotive design, the mass adoption of low carbon technologies represents a paradigm shift for the motorist. This paper aims to describe how the mapping of new parameters will lead to new transport scenarios that will create the space for new collaborative research on user experiences supported by innovative technologies and related services
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Matteo Maria Boiardo (1441-1494)
Matteo Maria Boiardo – contemporary of Sir Thomas Malory and forerunner of Shakespeare, Spenser, Milton, Cervantes, Tolkien, and C.S. Lewis – is best known as the author of the Orlando Innamorato [Orlando in Love], a poem in ottava rima organically merging Carolingian epic and Arthurian romance. He was also a lyric and pastoral poet, playwright, and translator of classical texts into the Italian vernacular. Matteo was active in Italy during the years of 1463 throughout 1494, the year of his death
Uno sguardo all'Est. Lavoro e diritti fondamentali in Russia e negli altri Paesi della Comunità di Stati indipendenti
Nel contributo l'autore, dopo aver esaminato i diritti fondamentali del lavoro presenti nelle Costituzioni dei Paesi della Comunità di Stati indipendenti, si sofferma sul diritto del lavoro russo. La trattazione, a carattere diacronico, abbraccia i rami principali del diritto del lavoro: il rapporto individuale, le relazioni collettive, il mercato del lavoro. L'autore rileva una sorprendente continuità nelle linee essenziali del diritto del lavoro russo, pur nel susseguirsi di sistemi socioeconomici completamente diversi. Egli conclude che il diritto del lavoro russo appartiene saldamente alla matrice europea della materia.The contribution of the author starts by examining fundamental labour rights recognised by the Constitutions of the Countries of the Community of Independent States. Then the author focuses upon Russian Labour Law, going through the history of the main branches of the discipline: the individual relationship, industrial relations, the labour market. The article finds a surprising continuity in the essential lines of Russian Labour Law, in spite of the completely different socio-economic systems that were experimented in Russia during the twentieth century. The author concludes that Russian Labour Law clearly belongs to the European matrix of the discipline
Corpo, spazio, architettura. Fenomenologia dell’esperienza spaziale Matteo Vegetti, Fabrizia Bandi (eds.), Editrice Morcelliana, Brescia 2024
The author reviews "Corpo, spazio, architettura: Fenomenologia dell’esperienza spaziale," edited by Matteo Vegetti and Fabrizia Bandi. The book examines the philosophical underpinnings of spatial experience through a phenomenological lens, engaging with both traditional and contemporary notions of how space, body, and architecture interconnect. The author highlights the text\u27s exploration of how architects and designers might integrate phenomenological insights into their work, transforming space from mere physical dimensions into lived, experienced reality. The review appreciates the book’s thematic organization, which starts with foundational theories from Merleau-Ponty and expands through discussions on virtual spaces and the future of architecture in the digital age. Through this anthology, readers gain a comprehensive view of the architectural implications of phenomenological thought, making it a critical resource for anyone involved in the conceptualization and design of space
An innovative infection method for the accumulation of viral nanoparticles in Nicotiana benthamiana
Tomato Bushy Stunt Virus (TBSV) naturally infects tomato plants, although it can also infect other plant species, such as Nicotiana benthamiana, a known model system in plant molecular farming. In the presented work, a novel system for TBSV infection of Nicotiana benthamiana plants, designed to produce nanomaterials, was developed and optimized based on a simple foliar spray, without the use of surfactants. Up to now, the standard procedures for the viral infection have been syringe or vacuum infiltration, which are a time-consuming manual procedure or requiring expensive machinery, respectively. The spraying method was chosen because it could be implemented in industrial conditions, such as vertical farms, where spraying systems are already present or can be easily installed at a low cost. In this work, as a proof of concept, a wild type and a modified version of TBSV construct, which generated a viral nanoparticle (VNP) exposing a small 12 aa-domain Liprin alpha 1 protein (Lip1) on each capsid protein, were successfully expressed in Nicotiana benthamiana plants. Specifically, VNP displaying Lip1 is a candidate for the treatment of rheumatoid arthritis. After 7 days of incubation, signs of viral infection were visible in the infected plants, while prolonged incubation time to 8 days significantly increased the accumulation of VNPs. The infection method described here offers straightforwardness and scalability of plant molecular farming, representing an efficient solution for the complexity of the conventional infection process
St. George and the Dragon or the town planner as a story-teller. In conversation with Bernardo Secchi about Il racconto urbanistico / Der heilige Georg und der Drache, oder: Der Stadtplaner als Geschichtenerzähler. Ein Gespräch mit Bernardo Secchi über Il racconto urbanistico
At the end of the second edition of his Storia dell’architettura italiana, Manfredo Tafuri declares that “one book assumes a crucial relevance”1 in finding a way out of the endemic crisis of modern architecture in the 1980s: Il racconto urbanistico. The publication of this work by the Italian urban planner 2 Bernardo Secchi in 1984 constitutes a unique event in recent European architecture—an event that still has not been appropriately described or analyzed. Matteo D’Ambros and Roberto Zancan met with the author to discuss the circumstances of the book’s publication. In a world of short memory, revisiting the possible contribution of literary studies to architecture and urban planning promises to shed light on the contemporary understanding of the disciplines. / Manfredo Tafuri schreibt am Ende der zweiten Auflage seiner Storia dell’architettura italiana, dass bei der Suche nach einem Ausweg aus der endemischen Krise der modernen Architektur in den 1980er Jahren „einem Buch entscheidende Bedeutung zukommt“1: Il racconto urbanistico. Die Ver öffentlichung dieses Werks des italienischen Stadtplaners 2 Bernardo Secchi im Jahr 1984 ist ein außergewöhnliches Ereignis in der neueren euro päischen Architektur – ein Ereignis, das noch nicht angemessen gewürdigt beziehungsweise analysiert worden ist. Matteo D’Ambros und Roberto Zancan trafen sich mit dem Autor, um über Aspekte rund um die Veröf fentlichung des Buches zu sprechen. In einer Welt mit kurzem Gedächtnis verspricht die erneute Betrachtung des Beitrags der Literaturwissenschaf ten zum Verständnis von Architektur und Stadt, neues Licht auf das berufliche Selbstverständnis zu werfen
Matteo Ricci's map and the centre around China
Matteo Ricci (1552-1610) was a Jesuit, an omniscient one: author, translator, theologian and mathematician. He was the first Westerner to translate Confucius into a European language and, most likely, the first Westerner to be admitted into the Forbidden City. His conversation and intellectual dialogues with Chinese intelligentsia are documented and well known. An unattributed version of the 1602 Kunyu Wanguo Quantu of Matteo Ricci Ricci was also a great cartographer whose work is still infl..
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