Italian National Institute of Biosystems and Biostructures

Rome, Italy

Italian National Institute of Biosystems and Biostructures

Rome, Italy
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Franconi F.,University of Sassari | Franconi F.,Italian National Institute of Biosystems and Biostructures | Campesi I.,Italian National Institute of Biosystems and Biostructures | Campesi I.,University of Sassari
British Journal of Pharmacology | Year: 2014

Pharmacological response depends on multiple factors and one of them is sex-gender. Data on the specific effects of sex-gender on pharmacokinetics, as well as the safety and efficacy of numerous medications, are beginning to emerge. Nevertheless, the recruitment of women for clinical research is inadequate, especially during the first phases. In general, pharmacokinetic differences between males and females are more numerous and consistent than disparities in pharmacodynamics. However, sex-gender pharmacodynamic differences are now increasingly being identified at the molecular level. It is now even becoming apparent that sex-gender influences pharmacogenomics and pharmacogenetics. Sex-related differences have been reported for several parameters, and it is consistently shown that women have a worse safety profile, with drug adverse reactions being more frequent and severe in women than in men. Overall, the pharmacological status of women is less well studied than that of men and deserves much more attention. The design of clinical and preclinical studies should have a sex-gender-based approach with the aim of tailoring therapies to an individual's needs and concerns. © 2013 The British Pharmacological Society.


Galistu A.,University of Sassari | D'Aquila P.S.,University of Sassari | D'Aquila P.S.,Italian National Institute of Biosystems and Biostructures
Psychopharmacology | Year: 2013

Rationale: We recently suggested that dopamine on D1-like receptors is involved in the activation of goal-directed responses and the level of response activation is "reboosted" on the basis of an evaluation process involving D2-like receptors assessing "response efficacy". A main piece of evidence in support of this hypothesis was the observation of an "extinction mimicry" effect in the time course of licking bursts after dopamine D2-like receptor blockade in rats licking for sucrose. Objectives: The aim of this study was to determine whether the pattern of licking observed with sucrose as a reward could be reproduced in rats licking for a different reward (0.9 % NaCl). Materials and methods: We investigated the effects of the dopamine D1-like receptor antagonist SCH 23390 (0.01-0.04 mg/kg) and of the dopamine D2-like receptor antagonist raclopride (0.025-0.25 mg/kg) on the microstructure of licking for a 0.9 % NaCl solution in 12-h water-deprived rats in 30-min sessions. Results: As previously observed with sucrose as a reward, raclopride reduced the size of licking bursts and produced on the burst number time course an "extinction mimicry" effect, while SCH 23390 reduced licking exclusively by reducing burst number. Conclusions: These results are consistent with the proposed hypothesis and provide support to the use of the study of licking microstructure as a valid model not only for the investigation of the mechanisms governing ingestive behaviour but also for the investigation of the mechanisms underlying behavioural activation and the related evaluation processes. © 2013 Springer-Verlag Berlin Heidelberg.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 1.30M | Year: 2009

Botrytis cinerea is a fungus that affects wine grapes and is responsible for the grey rot infection, which can strongly alter the quality of grapes and derived wine, causing: browning, destruction of flavour compounds, decrease of foaming properties, fermentation stopping. Grey rot is the largest infection of grapes in vineyards all over the world and is a major problem both for wine growers and wine producers, being very rapid and resistant to fungicides. The derived economic impact is disastrous, accounting for the loss of 15-40% of harvests, overcoming 15 billions of Euro per year (25% of the potential world wine production turnover). Quality control is usually done visually or through lab based analysis which need several minutes and are highly complex and expensive. The SAFEGRAPE aims to develop a simple and cheap instrument for the wine industry, able to provide a quantitative and reliable evaluation of the presence of grey rot infection in grapes in a very short time. The instrument is based on a biosensor system and on an innovative analysis method, that allows a precise and very fast analysis procedure, i.e. in less than one minute, which is compatible with the quality control procedures applied to grapes before wine-making (measure of total acidity, sugar content). The main result expected from the project is the development of the biosensor system integrated in 2 instruments: 1. portable instrument for the measure in vineyard, to be used by winegrowers in the field or after grape-harvest; 2. on-line instrument for quality control in wine production sites, to be integrated in the quality controls commonly applied (sugar and total acidity content). These instrumentations will allow to increase the wine quality and reduce the loss of harvest of about 10%, by a fast intervention in the field and is expected to have a market potential of several tens of millions of Euro for the SME proposers.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-10-2014 | Award Amount: 6.03M | Year: 2015

Cancer biomarkers circulating in body fluids have been shown to reflect the pathological process and for this reason can be used for cancer diagnosis, prognosis and choice for therapeutic interventions. It is proven that their detection is a key to new minimal-invasive detection approaches. However, barriers to wide spread use of similar approaches are lack of test sensitivity, specificity and limited availability of low cost detection platforms. This project is focused at developing a compact plasmonic-based device with integrated microfluidic circuit and functionalized nanostructures for the detection of DNA, microRNA and tumor autoantibodies cancer biomarkers. The aim is to detect cancer biomarkers circulating in blood with improvement in sensitivity of factor up to 1000, reduction in cost of platform of factor ranging from 2 to 4 compared to todays available techniques and analysis time less than 60 minutes. The proposed detection approache will provide ultrasensitive detection of biomolecular systems with no need for complex sample chemical modifications thus allowing direct and simple assays to be performed. Within the project a bimodal industrial prototype will be developed integrating novel surface plasmon resonance imaging and plasmon-enhanced fluorescence sensing technologies, respectively. Automated fabrication processes suitable for low cost mass production will be developed and applied to produce disposable integrated chips. Prototype will be specifically fabricated for early diagnosis and prognosis of colorectal cancer. The team includes partners holding cross-disciplinary competencies needed to achieve the proposed results, including two of the first five plasmon resonance groups in the world, the inventor of surface plasmon microscopy also known as surface plasmon resonance imaging- and plasmon-enhanced fluorescence spectroscopy, and full European value chain including disposable chip and readout platforms design, development and manufacturing.


Bucciantini M.,University of Florence | Rigacci S.,University of Florence | Stefani M.,University of Florence | Stefani M.,Italian National Institute of Biosystems and Biostructures
Journal of Physical Chemistry Letters | Year: 2014

Several human degenerative diseases involve amyloidogenic peptides/proteins with high conformational plasticity and propensity to self-aggregate into polymeric fibrillar assemblies sharing the cross-β structure and endowed with cytotoxic potential. Although the mechanisms of amyloid growth and toxicity are not fully understood, a common property of amyloids is their ability to interact with lipid bilayers disturbing membrane integrity. Lipid bilayers can also act as conformational catalysts, favoring protein misfolding and inducing the growth of aggregation nuclei, early oligomers, and mature fibrils with specific biophysical, structural, and toxicity features. This Perspective will highlight these effects in the context of a membrane-oligomer system where the conformational/biophysical features of either component affect those of the other. In this context, we will highlight the modulation of the protein-cell surface interaction by the content of membrane cholesterol and gangliosides, notably GM1. In particular, we will discuss data that indicate how these interactions affect the structural and stability properties of both protein and bilayers as well as the final cytotoxic effect. Our goal is to propose shared membrane-based mechanisms that could apply to any amyloidogenic peptide/protein, providing a biochemical background for amyloid growth and toxicity. © 2014 American Chemical Society.


Peracchi A.,University of Parma | Mozzarelli A.,University of Parma | Mozzarelli A.,Italian National Institute of Biosystems and Biostructures
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2011

The concept of allostery was elaborated almost 50 years ago by Monod and coworkers to provide a framework for interpreting experimental studies on the regulation of protein function. In essence, binding of a ligand at an allosteric site affects the function at a distant site exploiting protein flexibility and reshaping protein energy landscape. Both monomeric and oligomeric proteins can be allosteric. In the past decades, the behavior of allosteric systems has been analyzed in many investigations while general theoretical models and variations thereof have been steadily proposed to interpret the experimental data. Allostery has been established as a fundamental mechanism of regulation in all organisms, governing a variety of processes that range from metabolic control to receptor function and from ligand transport to cell motility. A number of studies have shed light on how evolutionary pressures have favored and molded the development of allosteric features in specific macromolecular systems. The widespread occurrence of allostery has been recently exploited for the development and design of allosteric drugs that bind to either physiological or non-physiological allosteric sites leading to gain of function or loss of function. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches. © 2010 Elsevier B.V. All rights reserved.


Idili A.,University of Rome Tor Vergata | Idili A.,Italian National Institute of Biosystems and Biostructures | Vallee-Belisle A.,University of Montréal | Ricci F.,University of Rome Tor Vergata | Ricci F.,Italian National Institute of Biosystems and Biostructures
Journal of the American Chemical Society | Year: 2014

We have designed programmable DNA-based nanoswitches whose closing/opening can be triggered over specific different pH windows. These nanoswitches form an intramolecular triplex DNA structure through pH-sensitive parallel Hoogsteen interactions. We demonstrate that by simply changing the relative content of TAT/CGC triplets in the switches, we can rationally tune their pH dependence over more than 5 pH units. The ability to design DNA-based switches with tunable pH dependence provides the opportunity to engineer pH nanosensors with unprecedented wide sensitivity to pH changes. For example, by mixing in the same solution three switches with different pH sensitivity, we developed a pH nanosensor that can precisely monitor pH variations over 5.5 units of pH. With their fast response time (<200 ms) and high reversibility, these pH-triggered nanoswitches appear particularly suitable for applications ranging from the real-time monitoring of pH changes in vivo to the development of pH sensitive smart nanomaterials. © 2014 American Chemical Society.


Mariani S.,University of Florence | Minunni M.,University of Florence | Minunni M.,Italian National Institute of Biosystems and Biostructures
Analytical and Bioanalytical Chemistry | Year: 2014

In the last 20 years, surface plasmon resonance (SPR) and its advancement with imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis for label-free, sensitive, and real-time monitoring of biomolecular interactions. Thus, we report in this review the state of the art of clinical target detection with SPR-based biosensors in complex matrices (e.g., serum, saliva, blood, and urine) as well as in standard solution when innovative approaches or advanced instrumentations were employed for improved detection. The principles of SPR-based biosensors are summarized first, focusing on the physical properties of the transducer, on the assays design, on the immobilization chemistry, and on new trends for implementing system analytical performances (e.g., coupling with nanoparticles (NPs). Then we critically review the detection of analytes of interest in molecular diagnostics, such as hormones (relevant also for anti-doping control) and biomarkers of interest in inflammatory, cancer, and heart failure diseases. Antibody detection is reported in relation to immune disorder diagnostics. Subsequently, nucleic acid targets are considered for revealing genetic diseases (e.g., point mutation and single nucleotides polymorphism, SNPs) as well as new emerging clinical markers (microRNA) and for pathogen detection. Finally, examples of pathogen detection by immunosensing were also analyzed. A parallel comparison with the reference methods was duly made, indicating the progress brought about by SPR technologies in clinical routine analysis. © 2014 Springer-Verlag Berlin Heidelberg.


Spoto G.,University of Catania | Spoto G.,Italian National Institute of Biosystems and Biostructures | Minunni M.,University of Florence
Journal of Physical Chemistry Letters | Year: 2012

This Perspective discusses recent advances in the field of surface plasmon resonance imaging (SPRi) for the label-free, multiplex, and sensitive study of biomolecular systems. Large efforts have been made during the past decade with the aim of developing even more sensitive and specific SPRi-based platforms. Metal nanostructures have been used to enhance SPRi sensitivity and to build a specific SPR-active surface, while special effects such as long-range SPR have been investigated to develop more effective SPRi platforms. Here, we review some of the significant work performed with SPRi for the ultrasensitive detection of biomolecular systems and provide a perspective on the challenges that need to be overcome to enable the wide use of SPRi in emerging key areas such as health diagnostics and antidoping controls. © 2012 American Chemical Society.


Pasquali M.,Center De Recherche Public Gabriel Lippmann | Migheli Q.,Italian National Institute of Biosystems and Biostructures
International Journal of Food Microbiology | Year: 2014

This review summarises the genetic methods used for chemotype determination of the main Fusarium type B-trichothecene producing species. Literature on Fusarium chemotype epidemiology over the last 15 years is reviewed in order to describe temporal and spatial chemotype distribution of these fungi worldwide. Genetic approaches used for chemotype determination are also reviewed and discussed, highlighting successes and potential pitfalls of the technique. Results from both genetic and chemical approaches are summarised to compare reliability, advantages and limitations of the two methods. Potential applications of genetic chemotyping to toxigenic Fusarium species are evaluated in the light of improving food safety of agricultural products. The use of chemotype determination in population studies, toxin prediction as well as for breeding purpose is described. © 2014 .

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