Cancer-Associated Mutations of the Adenosine A2A Receptor Have Diverse Influences on Ligand Binding and Receptor Functions

The adenosine A_2A receptor (A_2AAR) is a class A G-protein-coupled receptor (GPCR). It is an immune checkpoint in the tumor micro-environment and has become an emerging target for cancer treatment. In this study, we aimed to explore the effects of cancer-patient-derived A_2AAR mutations on ligand binding and receptor functions. The wild-type A_2AAR and 15 mutants identified by Genomic Data Commons (GDC) in human cancers were expressed in HEK293T cells. Firstly, we found that the binding affinity for agonist NECA was decreased in six mutants but increased for the V275A mutant. Mutations A165V and A265V decreased the binding affinity for antagonist ZM241385. Secondly, we found that the potency of NECA (EC₅₀) in an impedance-based cell-morphology assay was mostly correlated with the binding affinity for the different mutants. Moreover, S132L and H278N were found to shift the A_2AAR towards the inactive state. Importantly, we found that ZM241385 could not inhibit the activation of V275A and P285L stimulated by NECA. Taken together, the cancer-associated mutations of A_2AAR modulated ligand binding and receptor functions. This study provides fundamental insights into the structure–activity relationship of the A_2AAR and provides insights for A_2AAR-related personalized treatment in cancer.     

Chitosan nanostructures deposited from solutions in carbonic acid on a model substrate as resolved by AFM

Chitosan macromolecules can be dissolved in water saturated with CO₂ under high pressure, i.e. in carbonic acid. This unique biocompatible solvent with acidity regulated by the variation of applied CO₂ pressure is rather promising for biomedical applications. In this work the main features of deposition of chitosan structures on the model substrate from solutions in this media were examined. After deposition on the mica surface, the obtained structures have been successfully visualised by atomic force microscopy (AFM). It has been found out that they adsorb as rather peculiar elongated objects with an average length of about 70?nm. Such conformations are believed to appear due to amphiphilic nature of chitosan semiflexible chains in agreement with recent theoretical findings. The well-defined geometry of the elongated monodispersed structures allows them to demonstrate some elements of liquid crystalline-like ordering.     

Reflection of light by a slab containing electrically small dielectric spheres

Theoriginal and theenhanced Maxwell-Garnett estimates for the permittivity of a particulate medium are applied to the reflection of light by a composite dielectric slab. The reflection coefficients for incident s and p polarizations are calculated and some curves are plotted and discussed.     

Fluorescence lifetime imaging of molecular rotors to map microviscosity in cells

Fluorescence liftime imaging （FLIM） of modified hydrophobic bodipy dyes that act as fluorescent molecular rotors shows that the fluorescence lifetime of these probes is a function of the microviscosity of their environment. Incubating cells with these dyes, we find a punctate and continuous distribution of the dye in cells. The viscosity value obtained in what appears to be endocytotic vesicles in living cells is around 100 times higher than that of water and of cellular cytoplasm.Time-resolved fluorescence anisotropy measurements also yield rotational correlation times consistent with large microviscosity values. In this way, we successfully develop a practical and versatile approach to map the microviscosity in cells based on imaging fluorescent molecular rotors.     

Gauge theory of fermions onR × S 3 spacetime

A Lorentz-invariant gauge theory for massive fermions on R × S ³ spacetime is built up. Using the symmetry of S ³,we obtain Dirac-type equation and derive the expression of the fermionic propagator. Finally, starting from the SU(N) gauge-invariant Lagrangian, we obtain the set of Dirac-Yang-Mills equations on R × S ³ spacetime, pointing out major differences from the Minkowskian case.     

Nonlinear theory of resonant beam-plasma interaction: Nonrelativistic case

Analytic and numerical methods are used to study the nonlinear dynamics of the resonant interaction between a dense nonrelativistic electron beam and a plasma in a spatially bounded system. Regimes such as collective (Raman) and single-particle (Thomson) Cherenkov effects are considered. It is shown that in the first case, the motion of both the beam and plasma electrons exhibits significant nonlinearities. However, because of the weak coupling between the beam and the plasma, the nonlinear dynamics of the instability can be studied analytically and it can be strictly shown that saturation of instability is caused by a nonlinear shift of the radiation frequency and loss of resonance. In the second case, the nonlinear instability dynamics can only be studied numerically. In this regime, at low beam densities significant nonlinearity is only observed in the motion of the beam electrons while the plasma remains linear and saturation of the instability is caused by trapping of beam electrons in the field of the beam-excited plasma wave.     

Non-relativistic quantum theory of stimulated Cherenkov radiation and Compton scattering in plasma

The stimulated processes in electron plasma, i.e., Cherenkov radiation by a nonrelativistic electron beam of longitudinal oscillations and Compton scattering of a transverse electromagnetic wave in plasma with quantum mode excitation (de Broglie wave), are considered in the three-wave approximation. The possibility of the occurrence of quantum oscillations is discussed.