Glycolipids that elicit IFN-γ-biased responses from natural killer T cells

Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, α-galactosyl ceramide (αGalCer), is a potential anticancer agent whose activity depends upon IFN-γ secretion. We report two analogs of αGalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-γ that correlates with detergent-resistant binding to CD1d and an increased stability of the lipid-CD1d complexes on antigen-presenting cells. Structural analysis on one of the analogs indicates that it is more deeply bound inside the CD1d groove, suggesting tighter lipid-CD1d interactions. To our knowledge, this is the first example in which structural information provides an explanation for the increased lipid-CD1d stability, likely responsible for the Th1 bias. We provide insights into the mechanism of IFN-γ-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.     

Experimental study of vertical stress profiles of a confined granular bed under static and dynamic conditions

In a wet agglomeration process inside a low shear mixer, the blade function is to induce i) homogenization of the liquid sprayed on the powder surface and ii) a stress field able to transfer the mechanical energy at the particle scale. In this work we study the mechanical state of a confined powder bed through the analysis of stress distributions (by force measurements) in a rectangular cell in two cases: for a classical model powder (i.e. glass beads) and a complex powder (i.e. wheat semolina). Two types of vertical stress profiles are obtained according to the type of measurements carried out in the powder bed, either locally (at different positions in the cell) or globally (at the entire base). The global vertical stress profile follows Janssen's model and the local vertical stress profile highlights a critical length, identified as the percolation threshold of the force network, and a shielding length near the bottom, which is similar to an influence length of the side walls. In the context of wet agglomeration, the results allow to consider the role of the characteristic lengths in the mixing bowl under vertical mechanical solicitation.     

Complementary Approaches to Imaging Subcellular Lipid Architectures in Live Bacteria Using Phosphorescent Iridium Complexes and Raman Spectroscopy

A family of three neutral iridium(III) tetrazolato complexes are investigated as bacterial imaging agents. The complexes offer a facile tuning of the emission colour from green (520 nm) to red (600 nm) in aqueous media, while keeping the excitation wavelength unchanged. The three complexes do not inhibit the bacterial growth of Bacillus Cereus, used as a model in this study, and exhibit extremely fast cellular uptake. After a minute incubation time, the nontoxic complexes show subcellular localisation in spherical structures identified as lipid vacuoles. Confocal Raman imaging has been exploited for the first time on live bacteria, to provide direct and label-free mapping of the lipid-enriched organelles within B. cereus, complementing the use of luminescent probes. Examination of the Raman spectra not only confirmed the presence of lipophilic inclusions in B. cereus but offered additional information about their chemical composition, suggesting that the lipid vacuoles may contain polyhydroxybutyrate (PHB).     

Phthalocyanine nanoparticle formation in supersaturated solutions

Self-organization of molecules in solution is an important natural and synthetic process, in particular for the preparation of nanomaterials. However, the mechanism of growth for solution-based nanoparticle formation is not always well understood. We present results that clarify these mechanisms in solutions of magnesium phthalocyanine in which the self-organization is induced by addition of a miscible nonsolvent. From simultaneous measurements of the sizes of the growing nanoparticles by photon correlation spectroscopy and the molecular concentration by absorption and fluorescence spectroscopy, we have found that the particles do not grow by molecular diffusion to the surfaces. These results suggest the importance of unstable clusters in the growth process. We also observed a strong dependence of the particle size on the initial concentration which we attribute to effects of the curvature of the solubility curve.     

The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide,Bifunctional Chelator,and Pharmacokinetics Modifying Linker

Therapeutic radiopharmaceuticals have been researched extensively in the last decade as a result of the growing research interest in personalized medicine to improve diagnostic accuracy and intensify intensive therapy while limiting side effects. Radiometal-based drugs are of substantial interest because of their greater versatility for clinical translation compared to non-metal radionuclides. This paper comprehensively discusses various components commonly used as chemical scaffolds to build radiopharmaceutical agents, i.e., radionuclides, pharmacokinetic-modifying linkers, and chelators, whose characteristics are explained and can be used as a guide for the researcher.