Liquid-liquid phase separation of a surfactant-solubilized membrane protein

Solubilization of membrane proteins requires surfactants, whose structural properties play a crucial role in determining the protein phase behavior. We show that ionization of a pH-sensitive surfactant, lauryldymethylamino-N-oxide, bound to the bacterial photosynthetic Reaction Center, induces protein phase segregation in micrometric "droplets." Liquid-liquid phase separation takes place in a narrow pH range, is promoted by increasing temperature, and vanishes by adding salt. After a fast initial droplet growth, the nearly arrested kinetics at a later stage leaves the system in a finely divided, long-lasting emulsified state.     

Transforming nonlocality into a frequency dependence: a shortcut to spectroscopy

Measurable spectra are often derived from contractions of many-body Green's functions. One calculates hence more information than needed. Here we present and illustrate an in principle exact approach to construct effective potentials and kernels for the direct calculation of electronic spectra. In particular, a dynamical but local and real potential yields the spectral function needed to describe photoemission. We discuss for model solids the frequency dependence of this "photoemission potential" stemming from the nonlocality of the corresponding self-energy.     

Lanthanide Identity Governs Guest-Induced Dimerization in LnIII[15-MC N(L-pheHA)-5])3+ Metallacrowns

Series of lanthanide-containing metallic coordination complexes are frequently presented as structurally analogous, due to the similar chemical and coordinative properties of the lanthanides. In the case of chiral (Ln^III[15-MC _N(L-pheHA)-5])³⁺ metallacrowns (MCs), which are well established supramolecular hosts, the formation of dimers templated by a dicarboxylate guest (muconate) in solution of neutral pH is herein shown to have a unique dependence on the identity of the MC's central lanthanide. Calorimetric data and nuclear magnetic resonance diffusion studies demonstrate that MCs containing larger or smaller lanthanides as the central metal only form monomeric host-guest complexes whereas analogues with intermediate lanthanides (for example, Eu, Gd, Dy) participate in formation of dimeric host-guest-host compartments. The driving force for the dimerization event across the series is thought to be a competition between formation of highly stable MCs (larger lanthanides) and optimally linked bridging guests (smaller lanthanides).     

Sensing the Anti-Epileptic Drug Perampanel with Paper-Based Spinning SERS Substrates

The applications of SERS in therapeutic drug monitoring, or other fields of analytical chemistry, require the availability of sensitive sensors and experimental approaches that can be implemented in affordable ways. In this contribution, we show the production of cost-effective SERS sensors obtained by depositing Lee-Meisel Ag colloids on filter paper either by natural sedimentation or centrifugation. We have characterized the morphological and plasmonic features of the sensors by optical microscopy, SEM, and UV-Vis spectroscopy. Such sensors can be used to quantify by SERS the anti-epileptic drug Perampanel (in the concentration range 1 × 10⁻⁴–5 × 10⁻⁶ M) by spinning them during the micro-Raman measurements on the top of a custom device obtained from spare part hard disk drives. This approach minimizes laser-induced heating effects and allows averaging over the spatial non-uniformity of the sensor.     

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.     

Constraining extended theories of gravity using Solar System tests

Solar System tests give nowadays constraints on the estimated value of the cosmological constant, which can be accurately derived from different experiments regarding gravitational redshift, light deflection, gravitational time-delay and geodesic precession. Assuming that each reasonable theory of gravitation should satisfy Solar System tests, we use these limits on the estimated value of the cosmological constant to constrain extended theories of Gravity, which are nowadays studied as possible theories for cosmological models and provide viable solutions to the cosmological constant problem and the explanation of the present acceleration of the Universe. We obtain that the estimated values, from Solar System tests, for the parameters appearing in the extended theories of Gravity are orders of magnitude bigger than the values obtained in the framework of cosmologically relevant theories.     

Direct observation of tunneling and nonlinear self-trapping in a single bosonic Josephson junction

We report on the first realization of a single bosonic Josephson junction, implemented by two weakly linked Bose-Einstein condensates in a double-well potential. In order to fully investigate the nonlinear tunneling dynamics we measure the density distribution in situ and deduce the evolution of the relative phase between the two condensates from interference fringes. Our results verify the predicted nonlinear generalization of tunneling oscillations in superconducting and superfluid Josephson junctions. Additionally, we confirm a novel nonlinear effect known as macroscopic quantum self-trapping, which leads to the inhibition of large amplitude tunneling oscillations.     

Multiplexed therapeutic drug monitoring of antipsychotics in dried plasma spots by LC‐MS/MS

In this work, a convenient method for the therapeutic monitoring of seven common antipsychotic drugs in “dried plasma spot” samples has been developed. It is based on the liquid chromatography tandem mass spectrometry technique, operating in multiple reaction monitoring mode, and a straightforward procedure for the simultaneous extraction of all antipsychotics in a single step, with high extraction yield. The method was fully validated with proper accuracy, precision, selectivity and sensitivity, for all the drugs. Limits of quantification were 0.12, 1.09, 1.46, 1.47, 5.70, 1.32, 1.33 µg/L for haloperidol, aripiprazole, olanzapine, quetiapine, clozapine, risperidone, and paliperidone, respectively. Accuracy, intra‐ and interday precision values were <10% for all drugs at all concentration levels examined. The method was tested in the analysis of 30 plasma samples from real patients for each drug. The proposed analytical approach, by combining practical and logistical advantages of microsampling with liquid chromatography tandem mass spectrometry analytical performance, could offer an ideal strategy for accurate and timely therapeutic drug monitoring of antipsychotic drugs in most clinical settings, even in remote centers and/or in out‐patient settings, bringing so many potential improvements in psychiatric patient care.     

Modified edge finite elements for photonic crystals

We consider Maxwell’s equations with periodic coefficients as it is usually done for the modeling of photonic crystals. Using Bloch/Floquet theory, the problem reduces in a standard way to a modification of the Maxwell cavity eigenproblem with periodic boundary conditions. Following [8], a modification of edge finite elements is considered for the approximation of the band gap. The method can be used with meshes of tetrahedrons or parallelepipeds. A rigorous analysis of convergence is presented, together with some preliminary numerical results in 2D, which fully confirm the robustness of the method. The analysis uses well established results on the discrete compactness for edge elements, together with new sharper interpolation estimates.