Transitions between Inherent Structures in Water

The energy landscape approach has been useful to help understand the dynamic properties of supercooled liquids and the connection between these properties and thermodynamics. The analysis in numerical models of the inherent structure (IS) trajectories -- the set of local minima visited by the liquid -- offers the possibility of filtering out the vibrational component of the motion of the system on the potential energy surface and thereby resolving the slow structural component more efficiently. Here we report an analysis of an IS trajectory for a widely-studied water model, focusing on the changes in hydrogen bond connectivity that give rise to many IS separated by relatively small energy barriers. We find that while the system \emph{travels} through these IS, the structure of the bond network continuously modifies, exchanging linear bonds for bifurcated bonds and usually reversing the exchange to return to nearly the same initial configuration. For the 216 molecule system we investigate, the time scale of these transitions is as small as the simulation time scale ($\approx 1$ fs). Hence for water, the transitions between each of these IS is relatively small and eventual relaxation of the system occurs only by many of these transitions. We find that during IS changes, the molecules with the greatest displacements move in small ``clusters'' of 1-10 molecules with displacements of $\approx 0.02-0.2$ nm, not unlike simpler liquids. However, for water these clusters appear to be somewhat more branched than the linear ``string-like'' clusters formed in a supercooled Lennar d-Jones system found by Glotzer and her collaborators.Comment: accepted in PR

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

Instrumentatio

Protein and solvent dynamics in hydrated Crambin

In this paper we present an high resolution Incoherent Quasi-elastic Neutron Scattering experiment on Crambin hydrated at h = 0.6g/g. Hydration was attained by using D2O and H2O, in order to separate the contribution of the protein from that of the water. The spectra were interpreted in terms of an elastic peak and a quasi-elastic lorentzian contribution. From the obtained EISF information about the number of fixed and mobile hydrogens are derived. For the latter, an estimation of the spanned spatial and temporal scales is provided. In the case of protein dynamics, the obtained results favourably compare with literature data on the conformational disorder found by X-ray diffraction on the crystalline sample. In the case of water dynamics, the data show a confinement effect on the diffusion of hydration water

A novel potential nanophototherapeutic based on the assembly of an amphiphilic cationic ß-cyclodextrin and an anionic porphyrin

The development of cyclodextrin nanoassemblies as useful carriers for photosensitizer drugs (PS) delivery in biological environment is a topic of increasing interest. In this paper, we present a spectroscopic investigation on a nanosystem based on an amphiphilic cationic ß-cyclodextrin derivative (CD-N) and an anionic porphyrin (TPPS). Nanoassemblies were prepared by hydration of an organic film containing the two species. The system was characterized by complementary techniques such as UV-vis, stationary and time-resolved fluorescence, and Dynamic Light Scattering (DLS) at different TPPS/CD-N molar ratios. Time-resolved fluorescence data showed that, at all the investigated molar ratios, TPPS is present both as self-aggregated species and monomers forming supramolecular adducts with CD-N. Moreover, DLS measurements evidenced families of aggregates having hydrodynamic radii ranging between 50 and 350 nm and the size distribution profile depending on the TPPS/CD-N molar ratio. At the highest CD-N concentration, the hydrodynamic radii of the aggregates were nearly the same as those of neat CD-N in the absence of TPPS (50 nm). No aging phenomena were registered, pointing out the high stability of these nanoassemblies in aqueous solution for at least a month. Preliminary studies on the internalization in tumoral cells and subsequent irradiation for PDT application were carried out. The results support the feasibility of these nanoaggregates to promote PS internalization in HeLa cells, inducing cell death upon visible light irradiation. © 2017 World Scientific Publishing Company.Peer Reviewe

The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs

The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2-O-oligo(ethyleneoxide)-6-hexadecylthio-)-beta-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion-solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100\% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy

Role of Bcl-2 expression for productive herpes simplex virus 2 replication

Herpes simplex viruses infect a variety of cells in vitro. However, not all infected cells sustain a fully productive replication of these viruses. We have shown that, in U937 monocytoid cells, herpes simplex virus 2 (HSV-2) causes a low-productive infection characterized by apoptosis as cytopathic effect at a late stage of infection. This effect was associated with a down-regulation of the Bcl-2 protein. We therefore asked whether destabilization of Bcl-2 expression could act as a limiting factor for the productive HSV-2 infection. We found that overexpression of Bcl-2 in U937 cells dramatically increased the capability of these cells to sustain a fully productive infection, while protecting against apoptosis induced by HSV-2. Overall, our data indicate that Bcl-2 expression acts as a regulator of HSV-2 replication. (c) 2006 Elsevier Inc. All rights reserved

Herpes simplex virus 2 causes apoptotic infection in monocytoid cells

Increasing evidence indicates that apoptosis can be associated with several viral infections, Here we demonstrate, that infection of monocytoid cells by Herpes simplex virus 2 (HSV-2) resulted, in time-and dose-dependent induction of apoptosis as an exclusive cytopathic effect, The phenomenon was confirmed using four different techniques, Conversely, apoptosis was not observed in the Vero cell line, Virus yield in monocytoid cells was delayed and reduced, although well detectable, in comparison with that observed in Vero cells, Nevertheless, released virions exhibited full infecting capability. Apoptosis induced by HSV-P was not inhibited by cycloheximide and only partially by an UV-treatment which completely abrogated infectivity. Virus-induced apoptosis was partly inhibited by indomethacin and was associated with a down-regulation of Bcl-2, A similar, but less pronounced, apoptosis-inducing effect in monocytoid cells was also observed with HSV-1 infection. Depending on the target cells, therefore, HSV could complete a cycle of infection which is characterized by apoptosis of infected cells

Signaling pathway used by HSV-1 to induce NF-kappa B activation - Possible role of herpes virus entry receptor A

We have previously demonstrated that wild-type herpes simplex virus type 1 (HSV-1), as well as nonreplicating UV-inactivated HSV-1, promptly activates the nuclear factor-kappa B (NF-kappa B) in U937 monocytoid cells and that glycoprotein D (gD) of HSV-1 is sufficient by itself to exert a similar effect. We then investigated the signaling pathway used by HSV-1 to initiate NF-kappa B activation and, particularly, whether our observation could be related to the capability of HSV-1-gD to directly stimulate NF-kappa B through its interaction with the herpes virus entry receptor A (HveA). Here we report that: (a) co-cultivation of U937 cells with an adherent cell line expressing wild-type gD on its surface led to increased NF-kappa B activation, while co-cultivation with the same adherent cell line expressing a mutated form of gD, lacking the capability to bind HveA, did not cause the same effect; (b) exposure to UV-inactivated HSV-1 induced the activation of NF-kappa B in HveA-expressing U937 and THP-1 cells, but not in non-HveA-expressing HEp-2 cells; and (c) activation of NF-KB in U937 and THP-1 cells exposed to soluble gD was inhibited by an antibody able to interfere with gD-HveA interaction. These results suggest that HSV1-gD-HveA interaction initiates a signal transduction pathway leading to NF-kappa B activation