Phospholamban generates cation selective ion channels

Phosholamban (PLN) is involved in the contractility of cardiac muscles by regulating the intracellular calcium concentration (Ca(2+)(cyt)) of cardiac myocytes. This occurs via a modulation of the sarco-/endoplasmic CaATPase (SERCA). In spite of high-resolution structures the molecular mode of PLN action is yet not known. In the present paper we readdress the question whether PLN proteins can generate ion channel activity. Reconstitution of PLN in planar lipid bilayers reveals single channel fluctuations, which are characterized by two conductance levels, long open/closed dwell times, moderate selectivity between monovalent cations and no perceivable Ca(2+) permeability. The PLN generated channel activity could be inhibited by a PLN antibody (abPLN) implying that the channel activity is indeed due to the inherent channel function of the PLN protein.     

Tethered bilayer lipid micromembranes for single-channel recording: the role of adsorbed and partially fused lipid vesicles

A mercury-supported bilayer lipid micromembrane was prepared by anchoring a thiolipid monolayer to a mercury cap electrodeposited on a platinum microdisc about 20 μm in diameter; a lipid monolayer was then self-assembled on top of the thiolipid monolayer either by vesicle fusion or by spilling a few drops of a lipid solution in chloroform on the cap and allowing the solvent to evaporate. Single-channel recording following incorporation of the alamethicin channel-forming peptide exhibits quite different features, depending on the procedure followed to form the distal lipid monolayer. The "spilling" procedure, which avoids the formation of adsorbed or partially fused vesicles, yields very sharp single-channel currents lasting only one or two milliseconds. These are ascribed to ionic flux into the hydrophilic spacer moiety of the thiolipid. Conversely, the vesicle-fusion procedure yields much longer single-channel openings analogous to those obtained with conventional bilayer lipid membranes, albeit smaller. This difference in behavior is explained by ascribing the latter single-channel currents to ionic flux into vesicles adsorbed and/or partially fused onto the tethered lipid bilayer, via capacitive coupling.     

Fluorescence imaging assisted by surface modes on dielectric multilayers

The scaling behavior of criticality for spin-1 XXZ chains with uniaxial single-ion-type anisotropy is investigated by employing the infinite matrix product state representation with the infinite time evolving block decimation method. At criticality, the accuracy of the ground state of a system is limited by the truncation dimension χ of the local Hilbert space. We present four evidences for the scaling of the entanglement entropy, the largest eigenvalue of the Schmidt decomposition, the correlation length, and the connection between the actual correlation length ξ and the energy. The result shows that the finite scalings are governed by the central charge of the critical system. Also, it demonstrates that the infinite time evolving block decimation algorithm by the infinite matrix product state representation can be a quite accurate method to simulate the critical properties at criticality.     

[4+2] Cycloaddition on densely functionalized cyclopentadiene

The Diels-Alder (DA) and hetero-Diels-Alder (HDA) reaction of N-(2,4-dicyano-1,5-dimethyl-3-phenylcyclopenta-2,4-dienyl)-2,2,2-trifluoroacetamide 1 can be conveniently used for the synthesis of biarylic and polycyclic compounds, depending on whether you use alkynes or alkenes as dienophiles. We observe a totally regioselectivity and endo-diastereoselectivity of the cycloaddition reactions.     

Palladium-catalyzed acylation and/or homo-coupling of aryl- and alkyl-acetylenes

Allyl or benzyl halides, through a Pd(0)-catalyzed reaction and under CO pressure, generate acyl-palladium/halides that, in the presence of a base and an aryl- and alkyl-acetylene, undergo nucleophilic acyl substitution giving conjugated acetylenic ketones. Diynes, resulting from alkyne/alkyne homo-coupling, were instead the main products in reactions performed without allyl or benzyl halides. Moreover, dimerization, trimerization, and cyclotrimerization reactions of acetylenes were observed in reaction carried out even without base.     

Universal Low-energy Behavior in a Quantum Lorentz Gas with Gross-Pitaevskii Potentials

We consider a quantum particle interacting with N obstacles, whose positions are independently chosen according to a given probability density, through a two-body potential of the form N²V (Nx) (Gross-Pitaevskii potential). We show convergence of the N dependent one-particle Hamiltonian to a limiting Hamiltonian where the quantum particle experiences an effective potential depending only on the scattering length of the unscaled potential and the density of the obstacles. In this sense our Lorentz gas model exhibits a universal behavior for N large. Moreover we explicitely characterize the fluctuations around the limit operator. Our model can be considered as a simplified model for scattering of slow neutrons from condensed matter.     

Potential Use of Tea Tree Oil as a Disinfectant Agent against Coronaviruses: A Combined Experimental and Simulation Study

The COVID-19 pandemic has highlighted the relevance of proper disinfection procedures and renewed interest in developing novel disinfectant materials as a preventive strategy to limit SARS-CoV-2 contamination. Given its widely known antibacterial, antifungal, and antiviral properties, Melaleuca alternifolia essential oil, also named Tea tree oil (TTO), is recognized as a potential effective and safe natural disinfectant agent. In particular, the proposed antiviral activity of TTO involves the inhibition of viral entry and fusion, interfering with the structural dynamics of the membrane and with the protein envelope components. In this study, for the first time, we demonstrated the virucidal effects of TTO against the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43), both used as surrogate models for SARS-CoV-2. Then, to atomistically uncover the possible effects exerted by TTO compounds on the outer surface of the SARS-CoV-2 virion, we performed Gaussian accelerated Molecular Dynamics simulations of a SARS-CoV-2 envelope portion, including a complete model of the Spike glycoprotein in the absence or presence of the three main TTO compounds (terpinen-4-ol, γ-terpinene, and 1,8-cineole). The obtained results allowed us to hypothesize the mechanism of action of TTO and its possible use as an anti-coronavirus disinfectant agent.     

The Partition of Unity Method for High-Order Finite Volume Schemes Using Radial Basis Functions Reconstruction

This paper introduces the use of partition of unity method for the develop-ment of a high order finite volume discretization scheme on unstructured grids for solv-ing diffusion models based on partial differential equations. The unknown function and its gradient can be accurately reconstructed using high order optimal recovery based on radial basis functions. The methodology proposed is applied to the noise removal prob-lem in functional surfaces and images. Numerical results demonstrate the effectiveness of the new numerical approach and provide experimental order of convergence.     

Virtual Screening of Natural Compounds as Potential PI3K-AKT1 Signaling Pathway Inhibitors and Experimental Validation

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI₃K/AKT pathway.