Multicolor Caged dSTORM Resolves the Ultrastructure of Synaptic Vesicles in the Brain

The precision of single‐molecule localization‐based super‐resolution microscopy, including dSTORM, critically depends on the number of detected photons per localization. Recently, reductive caging of fluorescent dyes followed by UV‐induced recovery in oxidative buffer systems was used to increase the photon yield and thereby the localization precision in single‐color dSTORM. By screening 39 dyes for their fluorescence caging and recovery kinetics, we identify novel dyes that are suitable for multicolor caged dSTORM. Using a dye pair suited for registration error‐free multicolor dSTORM based on spectral demixing (SD), a multicolor localization precision below 15 nm was achieved. Caged SD‐dSTORM can resolve the ultrastructure of single 40 nm synaptic vesicles in brain sections similar to images obtained by immuno‐electron microscopy, yet with much improved label density in two independent channels.     

Understanding the mechanism of DNA deactivation in ion therapy of cancer cells: hydrogen peroxide action*

Changes in the medium of biological cells under ion beam irradiation has been considered as a possible cause of cell function disruption in the living body. The interaction of hydrogen peroxide, a long-lived molecular product of water radiolysis, with active sites of DNA macromolecule was studied, and the formation of stable DNA-peroxide complexes was considered. The phosphate groups of the macromolecule backbone were picked out among the atomic groups of DNA double helix as a probable target for interaction with hydrogen peroxide molecules. Complexes consisting of combinations including: the DNA phosphate group, H₂O₂ and H₂O molecules, and Na⁺ counterion, were considered. The counterions have been taken into consideration insofar as under the natural conditions they neutralise DNA sugar-phosphate backbone. The energy of the complexes have been determined by considering the electrostatic and the Van der Waals interactions within the framework of atom-atom potential functions. As a result, the stability of various configurations of molecular complexes was estimated. It was shown that DNA phosphate groups and counterions can form stable complexes with hydrogen peroxide molecules, which are as stable as the complexes with water molecules. It has been demonstrated that the formation of stable complexes of H₂O₂-Na⁺-PO₄ ^- may be detected experimentally by observing specific vibrations in the low-frequency Raman spectra. The interaction of H₂O₂ molecule with phosphate group of the double helix backbone can disrupt DNA biological function and induce the deactivation of the cell genetic apparatus. Thus, the production of hydrogen peroxide molecules in the nucleus of living cells can be considered as an additional mechanism by which high-energy ion beams destroy tumour cells during ion beam therapy.     

Chiral 1,2,4-triazoles: stereoselective acylation and chlorination

Acyl groups are transferred from diverse N- and O-acyl derivatives of chiral 3,5-bis-(1-hydroxyethyl)-[1,2,4]-triazole to amino acid esters enantioselectively, with 7% to 68% ee, depending on the temperature conditions and nature of the reagents. Thionyl chloride replaced the hydroxyl groups of (S)-1-[4-amino-5-((S)-1-hydroxy-ethyl)-[1,2,4]-triazol-3-yl]-ethanol 3 stereospecifically with inversion, as confirmed by X-ray analysis, which also revealed unusual crystal structures with asymmetric units comprising three molecules of 4-amino-3,5-bis(R-1-chloroethyl)-1,2,4-triazole 5 and four of 3,5-bis((R)-1-chloroethyl)-1H-1,2,4-triazole 6.     

Spiro[3.3]heptane as a Saturated Benzene Bioisostere**

The spiro[3.3]heptane core, with the non-coplanar exit vectors, was shown to be a saturated benzene bioisostere. This scaffold was incorporated into the anticancer drug sonidegib (instead of the meta-benzene), the anticancer drug vorinostat (instead of the phenyl ring), and the anesthetic drug benzocaine (instead of the para-benzene). The patent-free saturated analogs obtained showed a high potency in the corresponding biological assays.     

Theoretical analysis of low-lying vibrational modes of free canonical 2-deoxyribonucleosides

The low-lying vibrational mode frequencies of 2-deoxyribonucleosides (DNs) below 200 cm⁻¹ were analyzed using the density functional theory. Three types of vibrational modes of DNs were observed: the motion of sugar and base with respect to each other as almost rigid fragments; the modes localized within the sugar or base fragments; and the collective vibrations involving deformation of both the sugar and the base. These modes clearly differ by order and frequencies. The population of the ground and excited vibrational levels was estimated. These values indicate that only 15–27% of the molecules possess a geometry close to equilibrium at every moment in time.     

Dynamic properties of microemulsions modified with homopolymers and diblock copolymers: the determination of bending moduli and renormalization effects

The properties of bicontinuous microemulsions, consisting of water, oil, and a surfactant, can be modified by the addition of diblock copolymers (boosting effect) and homopolymers (inverse boosting effect) or a combination of both. Here, the influence of the addition of homopolymers (PEP(X) and PEO(X), X=5k or 10k molecular weight) on the dynamics of the surfactant layer is studied with neutron spin echo spectroscopy (NSE). Combining the results with the previous findings for diblock copolymers allows for a better separation of viscosity and bending modulus effects. With the addition of homopolymers, a significant increase of the relaxation rate compared to the pure microemulsion has been observed. The influence on the bending rigidity kappa is measured with NSE experiments. Homopolymer addition reduces kappa by up to Deltakappa approximately -0.5k(B)T, whereas the diblock copolymer yields an increase of kappa by approximately 0.3k(B)T. Comparison of the bending moduli that are obtained by analysis of the dynamics to those obtained from small angle neutron scattering (SANS) sheds light on the different renormalization length scales for NSE and SANS. Variation of the surfactant concentration at otherwise constant conditions of homopolymer or diblock-copolymer concentration shows that NSE results are leading to the pure bending rigidity, while the renormalized one is measured with SANS.     

A review of the chemical manipulation of nanomaterials using solvents: Gelation dependent structures

The hydrolysis of Mg, Zr, and Ti alkoxides by water in solvent-alcohol mixtures has been examined in the absence of added acid or base catalysts, and herein, these data are reviewed. The presence of low dielectric constant solvents (benzene, toluene, or anisole), in varying ratios with methanol (or other alcohols), caused much more rapid gelation, subsequently yielding mesoporous materials with higher surface areas and larger pore volumes as fibrous, open web-like structures. The presence of high dielectric constant (polar aprotic) solvents such as acetone, acetonitrile, DMF, DMSO, or dimethyaniline was not effective in this way. A partial charge model was employed to explain why the low dielectric solvents forced more rapid hydrolysis, and it is concluded that the hydrolysis step is rate determining, approaching diffusion control, in this gelation process. The use of these “spectator solvents” helps simplify and enhance sol-gel and xerogel/aerogel synthesis schemes, and yields higher quality materials.     

On solutions of linear functional differential equations with linearly transformed argument on a semiaxis

We establish conditions under which solutions of a system of linear functional differential equations on a semiaxis are determined as solutions of a certain system of ordinary differential equations. __________ Translated from Ukrains’kyi Matematychnyi Zhurnal, Vol. 59, No. 4, pp. 501–513, April, 2007.