Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity

Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]⁶-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT₂R/AT₁R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2 , has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21.     

ToF-SIMS PCA analysis of Myrtus communis L.

Nowadays there is a growing interest of researchers for the application of sophisticated analytical techniques in conjunction with statistical data analysis methods to the characterization of natural products to assure their authenticity and quality, and for the possibility of direct analysis of food to obtain maximum information. In this work, time-of-flight secondary ion mass spectrometry (ToF-SIMS) in conjunction with principal components analysis (PCA) are applied to study the chemical composition and variability of Sardinian myrtle (Myrtus communis L.) through the analysis of both berries alcoholic extracts and berries epicarp. ToF-SIMS spectra of berries epicarp show that the epicuticular waxes consist mainly of carboxylic acids with chain length ranging from C20 to C30, or identical species formed from fragmentation of long-chain esters. PCA of ToF-SIMS data from myrtle berries epicarp distinguishes two groups characterized by a different surface concentration of triacontanoic acid. Variability in antocyanins, flavonols, α-tocopherol, and myrtucommulone contents is showed by ToF-SIMS PCA analysis of myrtle berries alcoholic extracts.     

Blow-Up Estimates at Horizontal Points and Applications

Horizontal points of smooth submanifolds in stratified groups play the role of singular points with respect to the Carnot-Carathéodory distance. When we consider hypersurfaces, they coincide with the well known characteristic points. In two step groups, we obtain pointwise estimates for the Riemannian surface measure at all horizontal points of C ^1,1 smooth submanifolds. As an application, we establish an integral formula to compute the spherical Hausdorff measure of any C ^1,1 submanifold. Our technique also shows that C ² smooth submanifolds everywhere admit an intrinsic blow-up and that the limit set is an intrinsically homogeneous algebraic variety.     

Hyperfine structure of Ho3+ levels and electron-phonon coupling in YPO4 single crystals

High resolution spectroscopy (the finest being 0.01 cm(-1)) was applied in the 75-25,000 cm(-1) and 9-300 K ranges to a 1 mol% holmium doped Y PO(4) single crystal with two purposes: (1) to study the hyperfine splitting of Ho(3+) energy levels of interest for possible quantum manipulation media and (2) to analyze the electron-phonon interaction. The hyperfine structure was clearly revealed for a high number of lines in a wide wavenumber range (up to ~21,500 cm(-1)) and for a large number of multiplets. Several hyperfine patterns were monitored, differing in the number of components (a maximum of 16 could be easily distinguished in a single beautiful pattern), in their separation, and in their relative statistical weight. These features were all understood in terms of a crystal-field model, whose results are in good agreement with experiments and account for the involved level symmetry, the type of transitions (electric and magnetic dipole allowed), and the contribution of a second-order (pseudoquadrupolar) hyperfine coupling between close levels. The electron-phonon interaction, investigated through the thermally induced line shift, was critically discussed in the framework of single phonon coupling and of two phonon Raman scattering models.     

Hidden order and low-energy excitations in NpO2

We investigate the nature of the hidden order parameter in the ordered phase of NpO2, which had been identified with a staggered arrangement of Gamma5 magnetic multipoles. By analyzing the existing experimental data, we show that the most likely driving order parameter is not provided by octupoles, as usually assumed, but rather by the rank-5 triakontadipoles. Calculations of the coupled dynamics of spins, Gamma5 quadrupoles, and Gamma5 triakontadipoles in the ordered phase enable us to analyze the resulting structure of low-energy excitations. We show that the powder inelastic neutron scattering cross section should contain, in addition to the already-observed peak at 6.5 meV, a second weaker peak at about 14 meV.     

Thermal and optical control of electronic states in a single layer of switchable paramagnetic molecules

The control of the charge distribution in a monolayer of switchable cobalt–dioxolene complexes undergoing Valence Tautomerism (VT) has been achieved by means of thermal and optical stimuli. Thiol-derivatised VT molecules have been grafted on polycrystalline gold surface as monolayers from solution. X-ray photoelectron spectroscopy and time-of-flight secondary ions mass spectrometry evidenced the formation of a covalent bond between intact VT molecules and the surface and excluded the presence of physisorbed molecules. X-ray absorption spectroscopy revealed that the temperature- and light-induced conversion profiles of the monolayer closely reproduce the ones found for the crystalline phase. This study demonstrates that a wet chemistry based approach allows to transfer switchable paramagnetic molecules at the nanoscale, widening the playground to develop new hybrid molecular based architectures for novel technologies.     

Neutral Lipid Content and Biomass Production in Skeletonema marinoi (Bacillariophyceae) Culture in Response to Nitrate Limitation

Microalgae are one of the most promising biodiesel feedstocks due to their efficiency in CO₂ fixation and high neutral lipid productivity. Nutrient–stress conditions, including nitrogen starvation, enhance neutral lipid content, but at the same time lead to a reduction of biomass. To maximize lipid production in the diatom Skeletonema marinoi, we investigated two different nitrogen starvation approaches. In the first experimental approach, inocula were effectuated in modified f/2 media with decreasing nitrogen concentration, while in the second experiment, nitrate concentration was gradually reduced through a collection/resuspension system in which the culture was periodically collected and resuspended in culture medium with a lower nitrate concentration. In the first approach, the neutral lipid accumulation was accompanied by a strong biomass reduction, as was expected, whereas the second experiment generated cultures with significantly higher neutral lipid content without affecting biomass production. The total proteins and total carbohydrates, which were also quantified in both experiments, suggest that in S. marinoi, neutral lipid accumulation during nutrient starvation did not derive from a new carbon partition of accumulated carbohydrates.