350 research outputs found
Nino Nannetti
Fotocopia di una fotografia di Nino Nannetti, nato a Bologna il 19 aprile 1906 e morto a Santander (Spagna) il 21 luglio 1937. Da lui prende il nome una Divisione partigiana.1 riproduzione fotomeccanic
Sviluppo e caratterizzazione di nuovi inibitori diretti contro la polimerasi dei virus dell'influenza di tipo A e B
Influenza (flu) is an airborne highly-infectious disease, characterized by high morbidity and significant mortality, especially in at-risk population (young children, elderly people, patients with chronic disease). Influenza type A (IAV) and type B (IBV) viruses, characterized by remarkable genetic instability and antigenic variability, are responsible for seasonal epidemics, which affect every year 15-20% of the world population. In addition, IAV is able to infect a wide variety of birds and mammals and as happened with the recent case of H1N1 swine flu, a genetic reassortment between viral genomic segments of different species may occur and cause pandemics. During the past century, the pandemics of Spanish flu (1918), Asian flu (1957) and Hong Kong flu (1968) caused millions of deaths worldwide. For these reasons IAV and IBV pose a large threat to public health and it is absolutely necessary have therapeutic agents effective against these viruses.
The therapeutic options currently available for influenza include vaccination and two distinct classes of anti-influenza drugs represented by the NA inhibitors and the M2 ion channel blockers. However, vaccines need to be reformulated each year due to the genetic variability of the virus and are not always protective. In addition, the production of a new vaccine takes several months, so it is highly unlikely that vaccination may be effective in preventing the spread of a rapidly emerging influenza pandemic. Oseltamivir (tamiflu) and zanamivir (relenza) are NA inhibitors and act by blocking the release of the viral particle from infected cells. Amantadine (symadine, symmetrel) and rimantadine (Flumadine) block the ion channel of the M2 protein, preventing viral uncoating and thus the release of genomic segments in the cytoplasm. These drugs, however, have several drawbacks, including considerable side effects, limited efficacy, significant limitations of administration and above all they are associated with a rapid emergence of drug-resistant viral strains. In fact, there no an effective antiviral therapy against influenza and thus there is a strong need for the development of new anti-influenza compounds, possibly endowed with an innovative mechanism of action.
An interesting target for the development of novel anti-influenza strategies is represented by the viral RNA polymerase; in fact, the influenza virus polymerase is a conserved element among different viral strains, as it is not subjected to genetic variability.
The influenza virus RNA polymerase is a heterocomplex which consists of three proteins (polymerase acid protein [PA], polymerase basic protein 1 [PB1] and polymerase basic protein 1 [PB2]). The three polymerase subunits interact each other, in particular PB1 interacts with PB2 and PA, while at the moment there is little evidence of an interaction between PB2 and PA. It has been shown that the PA/PB1 interaction is crucial for influenza virus replication: in fact, the inhibition of this interaction result in the inhibition of viral polymerase activity. The fact that the interface of PA-PB1 interaction is highly conserved among different IAV and IBV strains and that this interaction is essential for viral replication makes it a potential target for the development of novel anti-influenza compounds with broad-spectrum activity. Thanks to an in silico screening of a virtual library of small molecules, performed by our research group, we have identified a few compounds able to dissociate the interaction between PA and PB1 in vitro, at micromolar concentrations (Muratore et al., 2012a). The same compounds showed no cytotoxicity in cell lines, but at the same time exhibited only modest antiviral activities against IAV. The purpose of this project was to evaluate the binding modes of these compounds with the target and based on this information to design structural analogues, in order to increase the antiviral activity, preserving the absence of cytotoxicity and their peculiar mechanism of action. Once synthesized, these analogues have been tested in various experiments, in order to assess their ability to inhibit viral replication of IAV in plaque reduction assays (PRA), but also to determine their inhibitory effect on PA-PB1 interaction in ELISA and to investigate their possible cytotoxicity on cell lines in MTT assays. Among these, the compounds 70, T22 and T40 showed inhibitory effects on viral polymerase activity, with EC50 values comparable or even lower than that obtained with ribavirin (RBV), used as reference drug. Then, we also evaluated the antiviral activity of these analogues over the time; what emerged is that all compounds show a maximum of activity at 12 h post-infection (p.i.), but they still maintain the antiviral effects at 48 h pi. Moreover, the most promising analogues were able to inhibit the replication of a panel of several strains of IAV and IBV, including an oseltamivir-resistant clinical isolate, thus demonstrating to have anti-influenza broad-spectrum activity. In contrast, the same compounds showed no inhibitory effect on the replication of other DNA and RNA viruses, confirming to possess a specific mechanism of action. Finally, for some promising analogues, we made predictions and simulations of virtual interaction with the cavity of PA as well as studies to assess the possible variation of inhibitory activity against mutated PA targets in some key residues as compared to the wild-type (wt) PA. This has allowed us to delineate the structure-activity relationships (SAR) and to understand the binding modes of these inhibitors, obtaining useful suggestions for the design of new analogues characterized by a better fit into the PA cavity and thus a more potent antiviral activity. In conclusion, this study demonstrates the potential of these compounds as inhibitors of influenza virus RNA polymerase, which will be tested in next future in combinations with current anti-Flu drugs in order to evaluate possible synergistic effects. In addition, this work has led to the identification of a series of new scaffolds endowed with antiviral activity that will be further studied to develop a new generation of therapeutic agents capable to fight the infection by IAV and IBV
Homenagem à Professora Dulcimara Carvalho Nannetti
Dulcimara Carvalho Nannetti é professora do IFSULDEMINAS (Instituto Federal de Educação, Ciência e Tecnologia do Sul de Minas Gerais), campus Machado. Leciona a disciplina de solos no curso técnico em agropecuária; de fertilidade do solo na graduação em agronomia; de fertilidade do solo e nutrição de plantas no curso superior de tecnologia em cafeicultura; e de fertilidade do solo na pós-graduação em cafeicultura empresarial
Understanding the Future Green Workforce through a Corpus of Curricula Vitae from Recent Graduates
In view of the much-heralded ecological transition, to stay competitive and participate in the
collective effort to face global warming and climate change, organisations need to select employees
interested in and able to develop environmentally sustainable and innovative ideas. The existing
literature however does not present consistent nor concordant results on the effective interest,
involvement and expertise of Generation Z members – namely, the newest entrants into the
workforce – in green issues. This study presents a corpus-assisted methodology to explore the profile
of the upcoming workforce expected to present itself to companies. With CVs as one of the first
interfaces between candidate and company in the recruitment process, a purpose-built corpus
consisting of Curricula Vitae from recent graduates of the University of Modena and Reggio Emilia
was collected. Data is investigated through a Corpus-Assisted Discourse Studies (CADS) framework,
proposing a novel interaction between structured metadata and textual information. The original
contribution of this approach lies in the extraction of information from the narrative structure of CVs
which, guiding the evaluation and exploration of metadata, ensures that the knowledge value of the
data can be explored in a discursive manner and not reduced to lists of competences and
qualifications
Lo scavo dell'ex Farmacia Boscia a Pesaro: studio minero-geochimico a fini archeometrici dei materiali ceramici.
Zeolite-Nafion composites as ion conducting membrane materials
Composite membranes formed of zeolitic fillers embedded in Nafion can be made by evaporating the solvents from a suspension
of small zeolite crystals in a Nafion solution. Two natural zeolites were selected as fillers: chabazite and clinoptilolite. Membranes
with various zeolite content were obtained. Composite membranes with zeolite content up to 40 vol.% exhibited uniform
distribution of the zeolite fillers throughout the thickness, as ascertained by scanning electron microscopy (SEM), energy dispersive
X-rays absorption (EDX) and ion conductivity measurements. Although more brittle than Nafion, these composite sheets retain*/
when hydrated*/reasonable flexibility below 40 vol.% zeolite content. We have determined the hydrogen ion conductivity and the
permeability of methanol molecules through these membranes (in the H-form as well as in the Na-form) in the temperature
range 22/60 8C. We found that the presence of the zeolitic fillers in the membranes can bear notable changes of conductivity,
permeability and selectivity with respect to membranes made out of sole Nafion
A pole matching method for the analysis of frequency selective surfaces
In this work, a pole matching method is presented for the analytical reconstruction, from full-wave data, of the scattering properties of frequency selective surfaces (FSS). This method allows one to synthesize the scattering response of an FSS from the identification of a few parameters, which exhibits a weak dependence with respect to the angle of incidence. This property implies that the full-wave analysis of the FSS can be performed for a limited set of incidence directions, from which the overall response can be obtained by a simple and numerically efficient algorithm. The final outcome is an analytical form for the scattering matrix which may be conveniently used in ray-tracing algorithms, based on local flat-surface approximations of curved FSS
Recruiting the next generation: insights from a corpus study of job advertisements targeting Gen Z
In a context marked by complex and rapidly changing circumstances, Generation Z (Gen Z) – comprising individuals born between 1995 and 2010 – is entering the workforce in increasing numbers. As the newest cohort of labour market participants, Gen Z has gained growing attention in discussions about workplace needs, expectations, and values. It has been observed that this generation places a high value on cultural alignment with their prospective workplace, making it essential for companies to engage effectively with them from the very first point of contact, namely the job posting. Job advertisements not only inform potential applicants about vacancies but also reflect contemporary employment culture and organisational values. These texts project an image of the company, its workforce, and the nature of the expected collaboration. In the specific context of organisational research on recruitment practices, person-organisation (P-O) fit can be considered as the match between an applicant and the broader organisational traits. This study investigates the relationship between the profile of the Generation Z workforce and the organisational identity, values, and culture conveyed through job advertisements targeting this generation, focusing on whether there is fit or misfit between the two. To effectively respond to the research question, a Corpus-Assisted Discourse Studies (CADS) approach is proposed to analyse a corpus of online job advertisements collected from a job board designed for students and recent graduates. Preliminary findings provide insights into how companies approach job advertising for Gen Z, identifying areas of alignment with
young people's values as well as elements of misalignment
- …
