Study of the conformational behaviour of trehalose mycolates by FT-IR spectroscopy.

Mycolic acids are fundamental cell wall components, found in the outer membrane barrier (mycomembrane) of Mycobacterium related genera, that have shown antigenic, murine innate immunity inducting and inflammatory activity triggering action. The mycolic acid derivatives, such as the lipid extractable trehalose monomycolates (TMM) and dimycolates (TDM), have been extensively investigated by several biochemical and biological methods and, more recently, we have performed the first neutron scattering measurements on these molecules in order to characterize their dynamical behavior as well as their rigidity properties. In the present paper, we show the first systematic FT-IR study on TMM, TDM and glucose monomycolate (GMM).

Resolution-elastic neutron scattering by correlation techniques.

Neutron scattering applications often require discriminating the elastic contribution from the inelastic contribution. For this purpose, correlation spectroscopy offers an effective tool with both pulsed and continuous neutron sources as well as several advantages: the analysis of the neutron velocity distribution can be carried out with a duty factor of 50%, independently on the resolution value; the best statistical accuracy for spectra where the elastic part encompasses most of the integrated intensity is provided. Depending on the statistical chopper position, correlation analysis can be used for both incoming and outgoing neutron velocity determination.

Leonardo da Vinci: Cause, effect, linearity, and memory.

In this contribution, some textual portions of the Leonardo da Vinci's work were analyzed with the aim to highlight how, moving from Aristotle and going beyond him, he combines the intermediate positions that, from the Greek philosopher, passing through Buridan, arrive to Newton. This has been performed following a path that passes through the formulation of the principle of causality, the use of the concept of linear relationship (pyramidal law) between cause and effect and the introduction of a duration of the impression (memory) of mechanical systems. In the framework of the studies aimed to a valorization of Leonardo as a scientist, which is a crucial aspect in the analysis of the Leonardo genius, the present work sheds a new light on his intuitions about some fundamental physics concepts as well as about the conceptual model that, several centuries later, will be formalized in the modern linear response theory.

Protein dynamics as seen by (quasi) elastic neutron scattering.

Background: Elastic and quasielastic neutron scattering studies proved to be efficient probes of the atomic mean square displacement (MSD), a fundamental parameter for the characterization of the motion of individual atoms in proteins and its evolution with temperature and compositional environment.

Scope Of Review: We present a technical overview of the different types of experimental situations and the information quasi-elastic neutron scattering approaches can make available. In particular, MSD can crucially depend on the time scale over which the averaging (building of the "mean") takes place, being defined by the instrumental resolution.

Contrasting dynamics of fragile and non-fragile polyalcohols through the glass, and dynamical, transitions: A comparison of neutron scattering and dielectric relaxation data for sorbitol and glycerol.

Background: Glycerol and sorbitol are glass-forming hydrogen-bonded systems characterized by intriguing properties which make these systems very interesting also from the applications point of view. The goal of this work is to relate the hydrogen-bonded features, relaxation dynamics, glass transition properties and fragility of these systems, in particular to seek insight into their very different liquid fragilities.

Methods: The comparison between glycerol and sorbitol is carried out by collecting the elastic incoherent neutron scattering (EINS) intensity as a function of temperature and of the instrumental energy resolution.

Biochemical and biophysical methodologies open the road for effective schistosomiasis therapy and vaccination.

Background: Schistosomiasis caused by blood-dwelling flukes, namely Schistosoma mansoni and Schistosoma haematobium is a severe debilitating disease, widespread in sub-Saharan Africa, the Middle East, and South America. Developing and adult worms are unscathed by the surrounding immune effectors and antibodies because the parasite is protected by a double lipid bilayer armor which allows access of nutrients, while binding of specific antibodies is denied.

Scope Of Review: Fluorescence recovery after bleaching, extraction of surface membrane cholesterol by methyl-β-cyclodextrin, inhibition and activation of sphingomyelin biosynthesis and hydrolysis, and elastic incoherent and quasi-elastic neutron scattering approaches have helped to clarify the basic mechanism of this immune evasion, and showed that sphingomyelin (SM) molecules in the worm apical lipid bilayer form with surrounding water molecules a tight hydrogen bond barrier.

Dynamical properties of α-synuclein in soluble and fibrillar forms by Quasi Elastic Neutron Scattering.

In the present paper, Quasi Elastic Neutron Scattering (QENS) results, gathered at different energy resolution values at the ISIS Facility (RAL, UK), on α-synuclein in soluble and fibrillar forms as a function of temperature and exchanged wave-vector Q are shown. The measurements reveal a different dynamic behavior of the soluble and fibrillar forms of α-synuclein as a function of thermal stress. In more detail, the dynamics of each protein form reflects its own complex conformational heterogeneity.

Mobility and temperature resistance of trehalose mycolates as key characteristics of the outer membrane of Mycobacterium tuberculosis.

Trehalose mycolates are fundamental characteristics of the outer membrane (mycomembrane) of Mycobacterium tuberculosis and they are supposed to play a key role in the low permeability and high resistance of mycobacteria to many antibiotics; however, still, the molecular characteristics making mycolates so effective in their biological function are not fully understood. This work aims to investigate by quasi-elastic neutron scattering the diffusive dynamical properties of trehalose mycolates in water mixtures as a function of temperature, energy and exchanged wavevector Q in order to elucidate the dynamics-function relation in the mycomembrane. A comparison with lecithin lipids in water mixtures is performed since they are considered among the most rigid and resistant lipids.

Rigidity and resistance of larval- and adult schistosomes-medium interface.

Schistosomiasis is second only to malaria in prevalence and severity, and is still a major health problem in many tropical countries worldwide with about 200-300 million cases and with more than 800 million people at risk of infection. Based on these data, the World Health Organization recommends fostering research efforts for understanding at any level the mechanisms of the infection and then decreasing the social and economical impact of schistosomiasis. A key role is played by the parasite apical lipid membrane, which is entirely impervious to the surrounding elements of the immune system.

FTIR, ESI-MS, VT-NMR and SANS study of trehalose thermal stabilization of lysozyme.

Protein aggregation is often associated with conformational and structural changes of secondary structure elements that may lead to exposure of some specific residues. Data obtained in our experimental work indicate that trehalose (1.0M) effectively prevent thermal inactivation and aggregation of lysozyme.

Is there a sphingomyelin-based hydrogen bond barrier at the mammalian host-schistosome parasite interface?

Schistosomes develop, mature, copulate, lay eggs, and live for years in the mammalian host bloodstream, importing nutrients across the tegument, but entirely impervious to the surrounding elements of the immune system. We have hypothesized that sphingomyelin (SM) in the parasite apical lipid bilayer is responsible for these sieving properties via formation of a tight hydrogen bond network with the surrounding water. Here we have used quasi-elastic neutron scattering for characterizing the diffusion of larval and adult Schistosoma mansoni and adult Schistosoma haematobium in the surrounding medium, under various environmental conditions.

Innovative wavelet protocols in analyzing elastic incoherent neutron scattering.

Wavelet analysis has recently found a wide range of applications in Physics, Mathematics, and signal processing. This is mainly due to its ability to locally resolve a nonstationary signal in terms of functional forms, called mother wavelets, and to firmly locate trend anomalies in the signal. In the present paper, some examples of the application of wavelet analysis to elastic incoherent neutron scattering (EINS) data collected by the IN13 spectrometer at the Institute Laue Langevin (ILL) on water mixtures of the three homologous disaccharides, trehalose, maltose, and sucrose, and on literature data of dry and hydrated lysozyme and myoglobine as a function of temperature and of exchanged wave vector are presented.

Molecular mechanisms of survival strategies in extreme conditions.

Today, one of the major challenges in biophysics is to disclose the molecular mechanisms underlying biological processes. In such a frame, the understanding of the survival strategies in extreme conditions received a lot of attention both from the scientific and applicative points of view. Since nature provides precious suggestions to be applied for improving the quality of life, extremophiles are considered as useful model-systems.

Elastic incoherent neutron scattering operating by varying instrumental energy resolution: principle, simulations, and experiments of the resolution elastic neutron scattering (RENS).

The main aim of this paper is to present the scientific case of the resolution elastic neutron scattering (RENS) method that is based on the collection of elastic neutron scattering intensity as a function of the instrumental energy resolution and that is able to extract information on the system dynamical properties from an elastic signal. In this framework, it is shown that in the measured elastic scattering law, as a function of the instrumental energy resolution, an inflection point occurs when the instrumental energy resolution intersects the system relaxation time, and in an equivalent way, a transition in the temperature behavior of the measured elastic scattering law occurs when the characteristic system relaxation time crosses the instrumental energy resolution time. With regard to the latter, an operative protocol to determine the system characteristic time by different elastic incoherent neutron scattering (EINS) thermal scans at different instrumental energy resolutions is also proposed.

Bio-protective effects of homologous disaccharides on biological macromolecules.

In this contribution the effects of the homologous disaccharides trehalose and sucrose on both water and hydrated lysozyme dynamics are considered by determining the mean square displacement (MSD) from elastic incoherent neutron scattering (EINS) experiments. The self-distribution function (SDF) procedure is applied to the data collected, by use of IN13 and IN10 spectrometers (Institute Laue Langevin, France), on trehalose and sucrose aqueous mixtures (at a concentration corresponding to 19 water molecules per disaccharide molecule), and on dry and hydrated (H(2)O and D(2)O) lysozyme also in the presence of the disaccharides. As a result, above the glass transition temperature of water, the MSD of the water-trehalose system is lower than that of the water-sucrose system.

Vibrational properties of bioprotectant mixtures of trehalose and glycerol.

In this work vibrational spectra of mixtures of two glass-forming bioprotectant systems, i.e., trehalose and glycerol, are collected at very low temperature by using the indirect geometry time-of-flight (t.

Puzzle of protein dynamical transition.

Despite recent extensive efforts, the nature of the dynamics of biological macromolecules still remains unclear. In particular, contradicting models have been proposed for explaining the temperature behavior of the mean square displacement, MSD, and of the system relaxation time, τ. To solve this puzzle, different neutron scattering experiments with different instrumental energy resolutions were performed on dry and hydrated lysozyme.

Mean square displacements from elastic incoherent neutron scattering evaluated by spectrometers working with different energy resolution on dry and hydrated (H2O and D2O) lysozyme.

The main aim of the present paper is the evaluation of the effects of the instrumental energy resolution on the mean square displacement (MSD) obtained by elastic incoherent neutron scattering (EINS). In particular, this study is performed in the time domain, through the time-Fourier transform of the elastically scattered neutron intensity, and is mainly focused on the connection between the system MSD and the measured MSD. It is shown how in the case of EINS, the instrumental energy resolution gives rise to the time integration of the time-dependent system MSD function weighted in time by the resolution function.

Study of solvent-protein coupling effects by neutron scattering.

The present work aims to characterize the dynamical behavior of proteins immersed in bio-preserving liquids and glasses. For this purpose, the protein dUTPase was chosen, while the selected solvents were glycerol, a triol, and some homologous disaccharides, i.e.

Motion characterization by self-distribution-function procedure.

In the present paper a procedure for the biomolecular motion characterization based on the evaluation of the Mean Square Displacement (MSD), through the Self Distribution Function (SDF), is presented. In particular it will be shown how the MSD, which represents a good observable for the characterization of the dynamical properties in disordered systems, can be decomposed into partial contributions associated to the system dynamical processes within a specific spatial scale. It will be shown how the SDF procedure allows to evaluate both the total MSD and the partial MSDs through the total SFD and the partial SDFs.

Biomolecular motion characterization by a self-distribution-function procedure in elastic incoherent neutron scattering.

In the present paper we first focus on the role of the instrumental resolution in elastic incoherent neutron scattering (EINS) where the connection between the self-distribution function (SDF) and the measured EINS intensity profile is highlighted. Second we show how the SDF procedure, previously introduced, allows both the total and the partial mean-square displacement evaluations through the total and the partial SDFs. Finally, we compare the SDF and the Gaussian procedures, by applying the two approaches to EINS data collected, by the IN13 backscattering spectrometer (Institute Laue-Langevin, Grenoble), on aqueous mixtures of two homologous disaccharides, i.