Structural characterization of a new lipid/DNA complex showing a selective transfection efficiency in ovarian cancer cells

We investigated, for the first time, by using Energy Dispersive X-ray Diffraction, the structure of a new ternary cationic liposome formulated with dioleoyl trimethylammonium propane (DOTAP), 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE) and cholesterol (Chol) (DDC) which has been recently found to have a selective high gene transfer ability in ovarian cancer cells. Our structural results provide a further experimental support to the widely accepted statement that there is not a simple and direct correlation between structure and transfection efficiency and that the factors controlling cationic lipid/DNA (CL-DNA) complexes-mediated gene transfer depend not only on the formulations of the cationic liposomes and their thermodynamic phase, but also significantly on the cell properties. Received: 28 October 2002 / Accepted: 21 March 2003 / Published online: 15 April 2003 RID="a" ID="a"e-mail: a.congiu@caspur.it     

Modeling of waveguide UV-induced Bragg gratings with arbitrary apodization function: Tools for designing high-performance related devices

We present a semi-analytical modeling suitable for the investigation of the spectral characteristics of UV-waveguide Bragg gratings (UV-WBGs) having arbitrary apodization function and extending both in the film layer and in the overlayer. The modeling is based on a proper combination of coupled mode theory and transfer matrix formalism and provides a powerful tool for designing and simulation of complex UV-grating based structures. The results of a detailed investigation of UV-WBGs in doped silica based channel optical waveguides are presented and critical issues for upgrading the performances of related device are discussed. Validation of the modeling is provided by means of an extensive comparison between theoretical and experimental results relevant to UV-WBGs realized in phosphorous (P)- and boron (B)-doped silica based waveguides.     

Fluorous phase transfer catalysts: From onium salts to crown ethers

Fluorous quaternary ammonium and phosphonium salts, as well as fluorous macrocyclic ligands, such as crown and aza-crown ethers, have been gradually emerging as viable alternatives to classical phase transfer catalysts. The major results thus far obtained in this burgeoning field will be the focus of this review.     

Shotgun proteomic analytical approach for studying proteins adsorbed onto liposome surface

The knowledge about the interaction between plasma proteins and nanocarriers employed for in vivo delivery is fundamental to understand their biodistribution. Protein adsorption onto nanoparticle surface (protein corona) is strongly affected by vector surface characteristics. In general, the primary interaction is thought to be electrostatic, thus surface charge of carrier is supposed to play a central role in protein adsorption. Because protein corona composition can be critical in modifying the interactive surface that is recognized by cells, characterizing its formation onto lipid particles may serve as a fundamental predictive model for the in vivo efficiency of a lipidic vector. In the present work, protein coronas adsorbed onto three differently charged cationic liposome formulations were compared by a shotgun proteomic approach based on nano-liquid chromatography–high-resolution mass spectrometry. About 130 proteins were identified in each corona, with only small differences between the different cationic liposome formulations. However, this study could be useful for the future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins into body fluids.     

Biosystem response to soft-X-rays irradiation: non-monotonic effects in the relevant biological parameters of yeast cells

Summary Soft-X-rays irradiation of yeast cells allows selective interference with different cellular structures. The monitoring of different physical parameters leads to substantial variations in the response to X-rays showing that monotonicity should not be taken for granted. Also at INFM (Istituto Nazionale di Fisica della Materia).     

The use of dynamical networks to detect the hierarchical organization of financial market sectors

Two kinds of filtered networks: minimum spanning trees (MSTs) and planar maximally filtered graphs (PMFGs) are constructed from dynamical correlations computed over a moving window. We study the evolution over time of both hierarchical and topological properties of these graphs in relation to market fluctuations. We verify that the dynamical PMFG preserves the same hierarchical structure as the dynamical MST, providing in addition a more significant and richer structure, a stronger robustness and dynamical stability. Central and peripheral stocks are differentiated by using a combination of different topological measures. We find stocks well connected and central; stocks well connected but peripheral; stocks poorly connected but central; stocks poorly connected and peripheral. It results that the Financial sector plays a central role in the entire system. The robustness, stability and persistence of these findings are verified by changing the time window and by performing the computations on different time periods. We discuss these results and the economic meaning of this hierarchical positioning.     

Two-dimensional lipid mixing entropy regulates the formation of multicomponent lipoplexes

The mechanism of formation of multicomponent lipoplexes was investigated by means of synchrotron Small-Angle X-ray Diffraction (SAXD). Mixed lipid dispersions were prepared by mixing different populations of binary cationic liposomes. When adding DNA to mixed lipid dispersions, multicomponent lipoplexes spontaneously formed exhibiting structural properties, i.e., membrane thickness, surface charge density, and one-dimensional DNA packing density, intermediate between those of binary lipoplexes. These results suggested that DNA lets liposomes come into contact and fuse and that a complete lipid mixing at the molecular level occurs. The equilibrium structure of multicomponent lipoplexes was found to be unique and did not depend on the number and kind of populations composing lipid dispersion but only on the lipid species involved and on their relative molar ratio. According to recent theoretical models we identified two-dimensional lipid mixing entropy as the key factor regulating the existence of only multicomponent lipoplexes with ideally mixed lipid species.     

Changes in cerebral activity after decreased upper-limb hypertonus: an EMG-fMRI study

Objective

Whereas several studies have used functional magnetic resonance imaging (fMRI) to investigate motor recovery, whether therapy to decrease post-stroke hypertonus alters central motor patterns remains unclear. In this study, we used continuous electromyography (EMG)-fMRI to investigate possible changes in movement-related brain activation in patients receiving Botulinum toxin (BoNT-A) for hand-muscle hypertonus after chronic stroke.

Methods

We studied eight stroke patients all of whom had hemiparesis and associated upper-limb hypertonus. All patients underwent an fMRI-EMG recording and clinical-neurological assessment before BoNT-A and 5 weeks thereafter. The handgrip motor task during imaging was fixed across both patients and controls. The movements were metronome paced, movement amplitude and force were controlled with a plastic orthosis, dynamometer and EMG recording. An age-matched control group was recruited from among healthy volunteers underwent the same fMRI-EMG recording.

Results

Before BoNT-A, while patients moved the paretic hand, fMRI detected wide bilateral activation in the sensorymotor areas (SM1), in the supplementary motor area (SMA) and cerebellum. After BoNT-A blood oxygenation level-dependent (BOLD) activation decreased in ipsilateral and contralateral motor areas and became more lateralized. BOLD activation decreased also in ipsilateral cerebellar regions and in the SMA.

Conclusion

Changes in peripheral upper-limb hypertonus after BoNT-A were associated to an improvement in active movements and more lateralized and focalized activation of motor areas. The clinical and EMG-fMRI coregistration technique we used to study hand-muscle hypertonus in patients receiving BoNT-A after chronic stroke should be useful in future studies seeking improved strategies for post-stroke neurorehabilitation.     

Ferroxidase Activity in Eukaryotic Ferritin is Controlled by Accessory‐Iron‐Binding Sites in the Catalytic Cavity

Ferritins are iron‐storage nanocage proteins that catalyze the oxidation of Fe²⁺ to Fe³⁺ at ferroxidase sites. By a combination of structural and spectroscopic techniques, Asp140, together with previously identified Glu57 and Glu136, is demonstrated to be an essential residue to promote the iron oxidation at the ferroxidase site. However, the presence of these three carboxylate moieties in close proximity to the catalytic centers is not essential to achieve binding of the Fe²⁺ substrate to the diferric ferroxidase sites with the same coordination geometries as in the wild‐type cages.