Enhanced Biostability and Cellular Uptake of Zinc Oxide Nanocrystals Shielded with Phospholipid Bilayer

The widespread use of ZnO nanomaterials for biomedical applications, including therapeutic drug delivery or stimuli-responsive activation, as well as imaging, imposes a careful control over the colloidal stability and long-term behaviour of ZnO in biological media. Moreover, the effect of ZnO nanostructures on living cells, in particular cancer cells, is still under debate. This paper discusses the role of surface chemistry and charge of zinc oxide nanocrystals, of around 15 nm in size, which influence their behaviour in biological fluids and effect on cancer cells. In particular, we address this problem by modifying the surface of pristine ZnO nanocrystals (NCs), rich of hydroxyl groups, with positively charged amino-propyl chains or, more innovatively, by self-assembling a double-lipidic membrane, shielding the ZnO NCs. Our findings show that the prolonged immersion in simulated human plasma and in the cell culture medium leads to highly colloidally dispersed ZnO NCs only when coated by the lipidic bilayer. In contrast, the pristine and amine-functionalized NCs form huge aggregates after already one hour of immersion. Partial dissolution of these two samples into potentially cytotoxic Zn2+ cations takes place, together with the precipitation of phosphate and carbonate salts on the NCs’ surface. When exposed to living HeLa cancer cells, higher amounts of lipid-shielded ZnO NCs are internalized with respect to the other samples, thus showing a reduced cytotoxicity, based on the same amount of internalized NCs. These results pave the way for the development of novel theranostic platforms based on ZnO NCs. The new formulation of ZnO shielded with a lipid-bilayer will prevent strong aggregation and premature degradation into toxic by-products, and promote a highly efficient cell uptake for further therapeutic or diagnostic functions

Intra-oral compartment pressures: a biofunctional model and experimental measurements under different conditions of posture

Oral posture is considered to have a major influence on the development and reoccurrence of malocclusion. A biofunctional model was tested with the null hypotheses that (1) there are no significant differences between pressures during different oral functions and (2) between pressure measurements in different oral compartments in order to substantiate various postural conditions at rest by intra-oral pressure dynamics. Atmospheric pressure monitoring was simultaneously carried out with a digital manometer in the vestibular inter-occlusal space (IOS) and at the palatal vault (sub-palatal space, SPS). Twenty subjects with normal occlusion were evaluated during the open-mouth condition (OC), gently closed lips (semi-open compartment condition, SC), with closed compartments after the generation of a negative pressure (CCN) and swallowing (SW). Pressure curve characteristics were compared between the different measurement phases (OC, SC, CCN, SW) as well as between the two compartments (IOS, SPS) using analysis of variance and Wilcoxon matched-pairs tests adopting a significance level of α = 0.05. Both null hypotheses were rejected. Average pressures (IOS, SPS) in the experimental phases were 0.0, −0.08 (OC); −0.16, −1.0 (SC); −48.79, −81.86 (CCN); and −29.25, −62.51 (SW) mbar. CCN plateau and peak characteristics significantly differed between the two compartments SPS and IOS. These results indicate the formation of two different intra-oral functional anatomical compartments which provide a deeper understanding of orofacial biofunctions and explain previous observations of negative intra-oral pressures at rest

The interface between the stellar wind and interstellar medium around R Cassiopeiae revealed by far-infrared imaging

The circumstellar dust shells of intermediate initial-mass (about 1 to 8 solar masses) evolved stars are generated by copious mass loss during the asymptotic giant branch phase. The density structure of their circumstellar shell is the direct evidence of mass loss processes, from which we can investigate the nature of mass loss. We used the AKARI Infrared Astronomy Satellite and the Spitzer Space Telescope to obtain the surface brightness maps of an evolved star R Cas at far-infrared wavelengths, since the temperature of dust decreases as the distance from the star increases and one needs to probe dust at lower temperatures, i.e., at longer wavelengths. The observed shell structure and the star's known proper motion suggest that the structure represents the interface regions between the dusty wind and the interstellar medium. The deconvolved structures are fitted with the analytic bow shock structure to determine the inclination angle of the bow shock cone. Our data show that (1) the bow shock cone of 1 - 5 x 10^-5 solar masses (dust mass) is inclined at 68 degrees with respect to the plane of the sky, and (2) the dust temperature in the bow shock cone is raised to more than 20 K by collisional shock interaction in addition to the ambient interstellar radiation field. By comparison between the apex vector of the bow shock and space motion vector of the star we infer that there is a flow of interstellar medium local to R Cas whose flow velocity is at least 55.6 km/s, consistent with an environment conducive to dust heating by shock interactions.Comment: 7 pages, 2 figures, accepted for publication in Astronomy and Astrophysic

Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments