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.     

Hydrogen effect on the molecular weight distribution of polymers obtained by polymerization of ethylene and α-olefins over supported titanium-magnesium catalysts

Comparative data on the molecular weight distribution of polymers obtained by polymerization of ethylene, propylene and 1-hexene, and copolymerization of ethylene with α-olefins over the titanium-magnesium catalysts (TMC) in the absence and presence of hydrogen are presented. In contrast to the ethylene polymerization, in the cases of propylene and 1-hexene polymerization and copolymerization of ethylene with α-olefins, the hydrogen addition is characterized by noticeable narrowing of the molecular weight distribution (MWD) due to lower contribution of the MWD component with high molecular weight. This result is an evidence of the increased reactivity of TMC active sites producing high molecular weight poly-α-olefins and copolymers of ethylene with α-olefins in the chain transfer reaction with hydrogen. It is suggested that the increased reactivity of these sites in the transfer reaction with hydrogen appears after the 2,1-addition of α-olefin to the growing polymer chain.     

Telomere Length in Metaphase Chromosomes of Human Triploid Zygotes

The human lifespan is strongly influenced by telomere length (TL) which is defined in a zygote—when two highly specialised haploid cells form a new diploid organism. Although TL is a variable parameter, it fluctuates in a limited range. We aimed to establish the determining factors of TL in chromosomes of maternal and paternal origin in human triploid zygotes. Using Q-FISH, we examined TL in the metaphase chromosomes of 28 human triploid zygotes obtained from 22 couples. The chromosomes’ parental origin was identified immunocytochemically through weak DNA methylation and strong hydroxymethylation in the sperm-derived (paternal) chromosomes versus strong DNA methylation and weak hydroxymethylation in the oocyte-derived (maternal) ones. In 24 zygotes, one maternal and two paternal chromosome sets were identified, while the four remaining zygotes contained one paternal and two maternal sets. For each zygote, we compared mean relative TLs between parental chromosomes, identifying a significant difference in favour of the paternal chromosomes, which attests to a certain “imprinting” of these regions. Mean relative TLs in paternal or maternal chromosomes did not correlate with the respective parent’s age. Similarly, no correlation was observed between the mean relative TL and sperm quality parameters: concentration, progressive motility and normal morphology. Based on the comparison of TLs in chromosomes inherited from a single individual’s gametes with those in chromosomes inherited from different individuals’ gametes, we compared intraindividual (intercellular) and interindividual variability, obtaining significance in favour of the latter and thus validating the role of heredity in determining TL in zygotes. A comparison of the interchromatid TL differences across the chromosomes from sets of different parental origin with those from PHA-stimulated lymphocytes showed an absence of a significant difference between the maternal and paternal sets but a significant excess over the lymphocytes. Therefore, interchromatid TL differences are more pronounced in zygotes than in lymphocytes. To summarise, TL in human zygotes is determined both by heredity and parental origin; the input of other factors is possible within the individual’s reaction norm.     

Mechanisms of the Cytotoxic Effect of Selenium Nanoparticles in Different Human Cancer Cell Lines

In recent decades, studies on the functional features of Se nanoparticles (SeNP) have gained great popularity due to their high biocompatibility, stability, and pronounced selectivity. A large number of works prove the anticarcinogenic effect of SeNP. In this work, the molecular mechanisms regulating the cytotoxic effects of SeNP, obtained by laser ablation, were studied by the example of four human cancer cell lines: A-172 (glioblastoma), Caco-2, (colorectal adenocarcinoma), DU-145 (prostate carcinoma), MCF-7 (breast adenocarcinoma). It was found that SeNP had different concentration-dependent effects on cancer cells of the four studied human lines. SeNP at concentrations of less than 1 μg/mL had no cytotoxic effect on the studied cancer cells, with the exception of the A-172 cell line, for which 0.5 μg/mL SeNP was the minimum concentration affecting its metabolic activity. It was shown that SeNP concentration-dependently caused cancer cell apoptosis, but not necrosis. In addition, it was found that SeNP enhanced the expression of pro-apoptotic genes in almost all cancer cell lines, with the exception of Caco-2 and activated various pathways of adaptive and pro-apoptotic signaling pathways of UPR. Different effects of SeNP on the expression of ER-resident selenoproteins and selenium-containing glutathione peroxidases and thioredoxin reductases, depending on the cell line, were established. In addition, SeNP triggered Ca²⁺ signals in all investigated cancer cell lines. Different sensitivity of cancer cell lines to SeNP can determine the induction of the process of apoptosis in them through regulation of the Ca²⁺ signaling system, mechanisms of ER stress, and activation of various expression patterns of genes encoding pro-apoptotic proteins.     

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.     

Calorimetric study approach for crude oil combustion in the presence of clay as catalyst

In this research, the effect of heating rate and different clay concentrations on light and heavy crude oils in limestone matrix was investigated by differential scanning calorimeter (DSC). In DSC experiments, two main distinct reaction regions were identified in all of the crude oil + limestone matrix + catalyst, known as low- and high-temperature oxidation respectively. It was observed that addition of clay to porous matrix significantly affected the thermal characteristics and kinetics of different origin crude oils. The Borchardt and Daniels and ASTM kinetic methods were used to determine the kinetic parameters of the samples. It was observed that activation energies generated for the high-temperature oxidation region for crude oil and crude oil + clay mixtures were in the range of 148–370 kJmol^?1 for the Borchardt and Daniels method and 51–253 kJmol^?1 for ASTM methods.     

Totally analytical closure of space filtered Navier–Stokes for arbitrary Reynolds number: Part III. aFNS theory validation

ABSTRACT

For arbitrary Reynolds number Re, aFNS theory O(1; δ²; δ³) significance scaled state variable achieves analytical closure of rigorously space filtered thermal, multi-species Navier–Stokes (NS) conservation principle partial differential equation (PDE) system well-posed on bounded domains (Part I). Validation of boundary commutation error (BCE) and nonhomogeneous Dirichlet boundary condition (DBC) resolution strategies results in AD^h-GWS^h-BCE^h-DBC^h algorithm coupling with aFNS theory optimal Galerkin GWS^h?+?θTS CFD algorithm (Part II), including accuracy/convergence assessments. For Reynolds numbers ranging E+02 <Re?<?2E+04, aFNS theory fully coupled k?=?1 basis Galerkin CFD code generated a posteriori data enable theory quantitative validation. For assured laminar Re range, NS no-slip BC reduced and coupled aFNS theory code predicted quasi-steady thermal-velocity transition to periodic unsteady is validated via linear stability predicted critical Re. For Re exceeding assured laminar, theory coupled CFD data quantify spatial filtering annihilation of (laminar) NS predicted large wave number spectral content. For sufficiently large Re, coupled CFD code a posteriori data document first principles prediction of unsteady periodic wall attached velocity profile transitioning-from-laminar, then separation, fully turbulent profile reattachment followed by relaminarization. These large Re CFD data as well enable validation of perturbation theory O(1; δ²; δ³) significance scaled state variable, AD^h-GWS^h-DBC^h algorithm prediction of O(δ²) state variable non-homogeneous Dirichlet BC DOF data and in concert thoroughly quantify theory generated O(δ²; δ³) state variable distributions.     

Ru@Pt core–shell nanoparticles for methanol fuel cell catalyst: Control and effects of shell composition

The present work presents a method to encapsulate pre-synthesised Ru nanoparticles (NPs) by Pt using a polyol method without capping agents at various pH values (6, 7, 8 and 10). The structural and surface properties of the catalysts were characterised using X-ray diffraction, transmission electron microscopy, CO stripping, and energy-dispersive X-ray spectroscopy. The studies suggest that the pH during encapsulation of Ru by Pt plays an important role in controlling of shell composition. A core–shell catalyst with an alloy shell was obtained at a pH of 6, whereas a monometallic Pt shell was obtained at a pH of 10. The core–shell catalysts gave higher steady-state current for methanol oxidation: 10-fold higher for alloy shells and 5-fold higher for Pt-enriched shells compared to the pure Pt catalyst. It is suggested that the highest catalytic enhancement of the core–shell catalysts is obtained through the bi-functional character that dominates the alloy shells rather than the ligand-effect-promoted Pt-enriched shells.     

Performance comparison of two combined SOFC–gas turbine systems

A necessary step in the use of natural gas (methane) in solid oxide fuel cells (SOFCs) is its preliminary conversion to hydrogen and carbon monoxide. To perform methane conversion within fuel cells and avoid catalyst carbonization the molar ratio between methane and steam (or steam with carbon dioxide) should be 1:2 or higher at the SOFC inlet. In this article two possible technological approaches to provide this desirable ratio in a combined SOFC–gas turbine system are compared. The first approach involves generation of the required steam in the coupled gas turbine cycle. The second (which is more traditional) involves recycling some part of the exhaust gases around the anodes of the SOFC stack.     

Greenhouse gas emissions reduction by use of wind and solar energies for hydrogen and electricity production: Economic factors

This study addresses economic aspects of introducing renewable technologies in place of fossil fuel ones to mitigate greenhouse gas emissions. Unlike for traditional fossil fuel technologies, greenhouse gas emissions from renewable technologies are associated mainly with plant construction and the magnitudes are significantly lower. The prospects are shown to be good for producing the environmentally clean fuel hydrogen via water electrolysis driven by renewable energy sources. Nonetheless, the cost of wind- and solar-based electricity is still higher than that of electricity generated in a natural gas power plant. With present costs of wind and solar electricity, it is shown that, when electricity from renewable sources replaces electricity from natural gas, the cost of greenhouse gas emissions abatement is about four times less than if hydrogen from renewable sources replaces hydrogen produced from natural gas. When renewable-based hydrogen is used in a fuel cell vehicle instead of gasoline in a IC engine vehicle, the cost of greenhouse gas emissions reduction approaches the same value as for renewable-based electricity only if the fuel cell vehicle efficiency exceeds significantly (i.e., by about two times) that of an internal combustion vehicle. It is also shown that when 6000 wind turbines (Kenetech KVS-33) with a capacity of 350 kW and a capacity factor of 24% replace a 500-MW gas-fired power plant with an efficiency of 40%, annual greenhouse gas emissions are reduced by 2.3 megatons. The incremental additional annual cost is about $280 million (US). The results provide a useful approach to an optimal strategy for greenhouse gas emissions mitigation.