GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca²⁺, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.     

Aliphatic 18F-Radiofluorination: Recent Advances in the Labeling of Base-Sensitive Substrates**

Aliphatic fluorine-18 radiolabeling is the most commonly used method to synthesize tracers for PET-imaging. With an increasing demand for ¹⁸F-radiotracers for clinical applications, new labeling strategies aiming to increase radiochemical yields of established tracers or, more importantly, to enable ¹⁸F-labeling of new scaffolds have been developed. In recent years, increased attention has been focused on the direct aliphatic ¹⁸F-fluorination of base-sensitive substrates in this respect. This minireview gives a concise overview of the recent advances within this field and aims to highlight the advantages and limitations of these methods.     

Zero-Knowledge Argument for Simultaneous Discrete Logarithms

In Crypto 1992, Chaum and Pedersen introduced a protocol (CP protocol for short) for proving the equality of two discrete logarithms (EQDL) with unconditional soundness, which is widely used nowadays and plays a central role in DL-based cryptography. Somewhat surprisingly, the CP protocol has never been improved for nearly two decades since its advent. We note that the CP protocol is usually used as a non-interactive proof by using the Fiat-Shamir heuristic, which inevitably relies on the random oracle model (ROM) and assumes that the adversary is computationally bounded. In this paper, we present an EQDL protocol in the ROM which saves approximately 40% of the computational cost and approximately 33% of the prover??s outgoing message size when instantiated with the same security parameter. The catch is that our security guarantee only holds for computationally bounded adversaries. Our idea can be naturally extended for simultaneously showing the equality of n discrete logarithms with O(1)-size commitment, in contrast to the n-element adaption of the CP protocol which requires O(n)-size. This improvement benefits a variety of interesting cryptosystems, ranging from signatures and anonymous credential systems, to verifiable secret sharing and threshold cryptosystems. As an example, we present a signature scheme that only takes one (offline) exponentiation to sign, without utilizing pairing, relying on the standard decisional Diffie-Hellman assumption.     

Thermally induced microstructure and morphology transformations in molybdenum disulfide–octadecyltrimethylammonim layered nanocomposite

Microstructure of layered nanocomposite compound consisting of molybdenum disulfide single layers and the layers of octadecyltrimethylammonium molecules as well as the structure of destruction products of this hybrid compound were studied by high resolution transmission electron microscopy (HRTEM) and powder X-ray diffraction (XRD) techniques. Changes in composition, ordering and morphology of the host and guest layers of the compound occurring due to release of organic guest from the interlayer space of MoS₂ on heating or on action of electronic beam have been revealed. Removal of the guest was found to initiate formation in the initial layered structure of the packets consisting of a few MoS₂ layers which come close together within the distances of ca. 1–1.5 nm and 0.6–0.7 nm after heating at 250 °C and 400 °C, respectively. Leaving the guest also causes deformations of MoS₂ layers resulting in their non-flat geometry. At 400 °C, strong bending of a part of the sulfide layers with the radius as small as 3–4 nm was observed.     

Synthesis of trimethylolpropane esters of tall oil fatty acids and properties of polyurethane coatings on their basis

Tall oil fatty acids (TOFA) were esterified with trimethylolpropane (TMP) without a catalyst at different molar ratios of TMP to TOFA. A molar ratio was defined, at which a polyol stable in long-term storage, with the maximum content of TMP monoesters, was synthesized. Fourier transform infrared spectroscopy and gas chromatography were used for the identification of the polyols’ chemical structure and composition. Based on the synthesized polyols, polyurethane coatings were prepared. The effect of the isocyanate index and concentration of traditional Sn-based and less toxic Bi-based catalysts on the gel time of the polyurethane composition, and the mechanical and thermal properties of the coatings was studied. It was found that the new coatings had high tensile strength and modulus of elasticity, comparable with the strength and modulus of the polyurethane based on diethanolamides of TOFA. The initial temperature of decomposition of these coatings was higher than that of the polyurethanes based on esters of TOFA and a number of uralkyds. The coatings based on TMP esters of TOFA were obtained without the use of solvents, and potentially, these esters can be used in spray-applied VOC-free polyurethane coatings’ formulation.     

Size and shape influence of luminescent orthovanadate nanoparticles on their accumulation in nuclear compartments of rat hepatocytes

In this paper the process of nonfunctionalized negatively charged orthovanadate nanoparticle accumulation and redistribution in cells dependent on their shape and size was investigated. Aqueous colloidal solutions of nReVO₄:Eu^3 + (Re = Gd, Y, La) luminescent nanocrystals of different sizes and shapes have been synthesized. The average sizes of spherical particles were 2, 20, and 300 nm, of spindle-like particles – 22 × 6.3 nm, and of rod-like particles – 57 × 4.4 nm. Luminescence of nReVO₄:Eu^3 + nanocrystals was effectively excited by UV and visible irradiation. By means of luminescence microscopy and luminescence microspectroscopy, it has been revealed that spherical nanocrystals with an average diameter of 2 nm tend to accumulate mainly in the rat hepatocyte nuclei in situ and also in the isolated nuclei of these cells. An additional experiment has shown that nanoparticles reveal tropism to nuclear structural components. The penetration into nuclei does not require any modifications of the surface of nanoparticle and is governed by the shape and size of nanoparticle and also is determined by the cellular type.     

Analysis of the Earthʼs magnetic field variations on the basis of a wavelet-based approach

In the present paper we will discuss a new wavelet-based approach aimed at processing and analyzing different features of complex geomagnetic signals. This approach makes it possible to automatically extract different kinds of disturbances in the Earth?s magnetic field variations, which characterize solar activity and help to predict magnetic storms. In order to analyze geomagnetic signals wavelet packets are used in order to isolate local variations for quiet and perturbed periods and determine their intensity. Furthermore, a new automatic method of calculating the index of geomagnetic activity K is suggested on the basis of forming a quiet-day diurnal variation (Sq-curve). This method allows us to do calculations in the way that is closest to that developed by J. Bartels, who introduced the K-index in 1938. The results are compared with those obtained by INTERMAGNET and the original method of J. Bartels and the advantages of the suggested method are clearly demonstrated. For geomagnetic data collected in high-latitude regions of our planet it has become possible to reduce the error of estimating the K-index by 20% and unlike the technique used by INTERMAGNET here all the calculations can be done automatically. We will use geomagnetic signals that were kindly provided to us by the Institute of Cosmophysical Research and Radio Wave Propagation (Paratunka, Kamchatka region, Far East of Russia) for the period from January, 2002 till December, 2010.