Melatonin Prevents Early but Not Delayed Ventricular Fibrillation in the Experimental Porcine Model of Acute Ischemia

Antiarrhythmic effects of melatonin have been demonstrated ex vivo and in rodent models, but its action in a clinically relevant large mammalian model remains largely unknown. Objectives of the present study were to evaluate electrophysiological and antiarrhythmic effects of melatonin in a porcine model of acute myocardial infarction. Myocardial ischemia was induced by 40-min coronary occlusion in 25 anesthetized pigs. After ischemia onset, 12 animals received melatonin (4 mg/kg). 48 intramyocardial electrograms were recorded from left ventricular wall and interventricular septum (IVS). In each lead, activation time (AT) and repolarization time (RT) were determined. During ischemia, ATs and dispersion of repolarization (DOR = RTmax − RTmin) increased reaching maximal values by 3–5 and 20–25 min, respectively. Ventricular fibrillation (VF) incidence demonstrated no relations to redox state markers and was associated with increased DOR and delayed ATs (specifically, in an IVS base, an area adjacent to the ischemic zone) (p = 0.031). Melatonin prevented AT increase in the IVS base, (p < 0.001) precluding development of early VF (1–5 min, p = 0.016). VF occurrence in the delayed phase (17–40 min) where DOR was maximal was not modified by melatonin. Thus, melatonin-related enhancement of activation prevented development of early VF in the myocardial infarction model.     

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, the closo-dodecaborate anion represents a high-boron-containing residue with remarkable chemical stability and low toxicity, and is suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5′-, 3′-, or both terminal positions of DNA, RNA, 2′-O-Me RNA, and 2′-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3′-end of all oligomers stabilized their complementary complexes, whereas analogous 5′-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2′-O-methyl and 2′-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized the DNA/DNA duplex but gave a strong stabilization of the duplex with an RNA target. According to circular dichroism spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from the B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.     

Information avoidance: Who, what, when, and why.

Although acquiring information can provide numerous benefits, people often opt to remain ignorant. We define information avoidance as any behavior designed to prevent or delay the acquisition of available but potentially unwanted information. We review the various literatures that examine information avoidance and provide a unique framework to integrate the contributions of these disparate areas of research. We first define information avoidance and distinguish it from related phenomena. We then discuss the motivations that prompt information avoidance and the factors that moderate the likelihood of avoidance. Finally, we discuss individual differences that predict preferences for information avoidance. We conclude by evaluating the current state of research on information avoidance and discussing directions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Examining the process by which marital adjustment affects maternal warmth: The role of coparenting support as a mediator.

This study assessed the longitudinal process by which marital adjustment affects change in maternal warmth over time. Change in coparenting support was examined as the potential mechanism by which the marriage affects parenting. Self-report data were gathered from 148 married mothers of first-born 4th graders at 3 time points, over the transition to early adolescence. Path analyses supported the proposed hypothesis, indicating that marital adjustment leads to increased coparenting support, which then leads to increased maternal warmth. Two alternative models of the time-ordered direction of effects among the study variables were ruled out. This study has important implications for the development of parenting interventions targeting the promotion of maternal warmth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of ¹⁰B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying ¹⁰B to the tumor cells. This study represents the first example of using 2′-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The closo-dodecaborate residue was attached to the 5′-end of the aptamer, which was also labeled by the fluorophore at the 3′-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of ¹⁰B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.     

BaGdF5 Nanophosphors Doped with Different Concentrations of Eu3+ for Application in X-ray Photodynamic Therapy

X-ray photodynamic therapy (XPDT) has been recently considered as an efficient alternative to conventional radiotherapy of malignant tissues. Nanocomposites for XPDT typically consist of two components—a nanophosphor which re-emits X-rays into visible light that in turn is absorbed by the second component, a photosensitizer, for further generation of reactive oxygen species. In this study, BaGdF₅ nanophosphors doped with different Eu:Gd ratios in the range from 0.01 to 0.50 were synthesized by the microwave route. According to transmission electron microscopy (TEM), the average size of nanophosphors was ~12 nm. Furthermore, different coatings with amorphous SiO₂ and citrates were systematically studied. Micro-CT imaging demonstrated superior X-ray attenuation and sufficient contrast in the liver and the spleen after intravenous injection of citric acid-coated nanoparticles. In case of the SiO₂ surface, post-treatment core–shell morphology was verified via TEM and the possibility of tunable shell size was reported. Nitrogen adsorption/desorption analysis revealed mesoporous SiO₂ formation characterized by the slit-shaped type of pores that should be accessible for methylene blue photosensitizer molecules. It was shown that SiO₂ coating subsequently facilitates methylene blue conjugation and results in the formation of the BaGdF₅: 10% Eu³⁺@SiO₂@MB nanocomposite as a promising candidate for application in XPDT.     

Antimicrobial Properties and Cytotoxic Effect of Imidazolium Geminis with Tunable Hydrophobicity

Antimicrobial, membranotropic and cytotoxic properties of dicationic imidazolium surfactants of n-s-n (Im) series with variable length of alkyl group (n = 8, 10, 12, 14, 16) and spacer fragment (s = 2, 3, 4) were explored and compared with monocationic analogues. Their activity against a representative range of Gram-positive and Gram-negative bacteria, and also fungi, is characterized. The relationship between the biological activity and the structural features of these compounds is revealed, with the hydrophobicity emphasized as a key factor. Among dicationic surfactants, decyl derivatives showed highest antimicrobial effect, while for monocationic analogues, the maximum activity is observed in the case of tetradecyl tail. The leading compounds are 2–4 times higher in activity compared to reference antibiotics and prove effective against resistant strains. It has been shown that the antimicrobial effect is not associated with the destruction of the cell membrane, but is due to specific interactions of surfactants and cell components. Importantly, they show strong selectivity for microorganism cells while being of low harm to healthy human cells, with a SI ranging from 30 to 100.     

Fabrication of core-sheath nanoyarn via touchspinning and its application in wearable piezoelectric nanogenerator

Abstract

A simple and versatile touchspinning method is demonstrated for the fabrication of core-sheath nanofibrous piezoelectric yarns with a single filament electroconductive core. The polyvinylidene fluoride (PVDF) piezoelectric nanofibers are fabricated in a continuous spinning process with relatively controlled structure, orientation, and dimensions to form a sheath layer. The PVDF core-sheath nanoyarn is assembled into a piezoelectric nanogenerator (PNG) capable to convert mechanical energy of body motion into electricity. It was demonstrated that an electrical potential difference of 0.72?V can be generated under compression of 0.33?MPa for a single 3-cm long yarn. The touchspun nanoyarn fabrication method has great potential for the fabrication of functional smart textile products.     

Natural organic matter (NOM) induces oxidative stress in freshwater amphipods Gammarus lacustris Sars and Gammarus tigrinus (Sexton)

Humic substances comprise the majority of natural organic matter (NOM) on Earth, including dissolved organic matter in freshwater systems. Recent studies show that these substances directly interact with aquatic organisms as chemical stressors. The aim of the present study was to investigate the mode of action of dissolved NOM on the freshwater amphipods Gammarus lacustris Sars and Gammarus tigrinus (Sexton), and in particular, to determine if NOM induces or promotes internal oxidative stress. NOM was isolated by reverse osmosis from a brown-water lake in Brandenburg State, Germany. Oxidative stress markers, such as lipid peroxidation, cell internal hydrogen peroxide concentration, as well as peroxidase, catalase and glutathione S-transferase activities, were quantified. Exposure of both amphipod species to NOM caused a significant increase in lipid peroxidation, hydrogen peroxide concentration, catalase, peroxidase and glutathione S-transferase activities. Both species showed a two-stage antioxidant response: the first stage allowed the organisms to effectively eliminate ROS and to protect cells from damage, whereas the second stage leads to H2O2 accumulation in combination with destruction of lipid structures in the cells and, finally, functional damage or even death of the organism.