Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.     

Pt–Ru nanoparticles anchored on poly(brilliant cresyl blue) as a new polymeric support: Application as an efficient electrocatalyst in methanol oxidation reaction

The glassy carbon electrode is modified by poly(brilliant cresyl blue) (PBCB) to be applied as a new green and efficient platform for Pt and Pt–Ru alloy nanoparticles deposition. Surface composition, morphology and catalytic activity of these modified electrodes towards methanol oxidation are assessed by applying X-ray diffraction, field emission scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy techniques. The X-ray diffraction patterns reveal that the highly crystalline Pt and Pt–Ru alloy and RuO₂ nanoparticles with low crystallinity are deposited on the PBCB modified glassy carbon electrodes. The microscopic images indicate smaller size and better distribution of deposited nanoparticles on the surface of PBCB modified electrodes. Cyclic voltammetry and electrochemical impedance spectroscopy results reveal that PBCB supported Pt and Pt–Ru nanoparticles have better electrocatalytic performance and durability towards methanol oxidation rather than the unsupported nanoparticles. From the obtained results it can be concluded that the presence of PBCB not only improves the stability of nanoparticles on the surface, but also leads to the formation of smaller size and more uniform distribution of nanoparticles on the surface, which, in turn, cause the nanoparticles to provide a higher accessible surface area and more active centers for the oxidation of methanol. The results will be valuable in extending the applications of this polymer in surface modification steps and in developing promising catalyst supports to be applied in direct methanol fuel cells.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

Plasmonic-excitonic multi-hybrid glass-based nanocomposites incorporating Ag plus core-shell CdSe/CdS and alloyed CdSxSe1−x nanoparticles

Successful fabrication of glass-based hybrid nanocomposites (GHNCs) incorporating Ag, core-shell CdSe/CdS and CdS_xSe_1?x nanoparticles (NPs) is herein reported. Both metallic (Ag) and semiconductor (CdSe/CdS) NPs were pre-synthesized, suspended in colloids and added into the sol-gel reaction medium which was used to fabricate the GHNCs. During fabrication of the nanocomposites a fraction (20–60%) of core-shell CdSe/CdS NPs was alloyed into CdS_xSe_1?x (0.20 < x < 0.35) NPs without changing morphology. Modulation of in situ alloying is possible via the relative content of organics added into the sol-gel protocol. Within colloids Ag (core-shell CdSe/CdS) NPs presented average diameter and polydispersity index of 49.5 nm (4.2 nm) and 0.41 (0.21), respectively. On the other hand, the Ag (core-shell CdSe/CdS) NPs’ average diameter and polydispersity index assessed from the GHNCs were respectively 51.5 nm (4.1 nm) and 0.43 (0.25), revealing negligible aggregation of the nanophases within the glass template. The new GHNCs herein introduced presented two independent excitonic transitions associated to homogenously dispersed semiconductor NPs, peaking around 420 nm (core-shell CdSe/CdS) and 650 nm (CdS_xSe_1?x) and matching the plasmonic resonance (Ag NPs) in the 400–500 nm range. We envisage that the new GHNCs represent very promising candidates for superior light manipulation while illuminated with multiple laser beams in quantum interference-based devices.     

Impact of an Engineered Copper-Titanium Dioxide Nanocomposite and Parent Substrates on the Bacteria Viability,Antioxidant Enzymes and Fatty Acid Profiling

Due to the systematic increase in the production of nanomaterials (NMs) and their applications in many areas of life, issues associated with their toxicity are inevitable. In particular, the performance of heterogeneous NMs, such as nanocomposites (NCs), is unpredictable as they may inherit the properties of their individual components. Therefore, the purpose of this work was to assess the biological activity of newly synthesized Cu/TiO₂-NC and the parent nanoparticle substrates Cu-NPs and TiO₂-NPs on the bacterial viability, antioxidant potential and fatty acid composition of the reference Escherichia coli and Bacillus subtilis strains. Based on the toxicological parameters, it was found that B. subtilis was more sensitive to NMs than E. coli. Furthermore, Cu/TiO₂-NC and Cu-NPs had an opposite effect on both strains, while TiO₂-NPs had a comparable mode of action. Simultaneously, the tested strains exhibited varied responses of the antioxidant enzymes after exposure to the NMs, with Cu-NPs having the strongest impact on their activity. The most considerable alternations in the fatty acid profiles were found after the bacteria were exposed to Cu/TiO₂-NC and Cu-NPs. Microscopic images indicated distinct interactions of the NMs with the bacterial outer layers, especially in regard to B. subtilis. Cu/TiO₂-NC generally proved to have less distinctive antimicrobial properties on B. subtilis than E. coli compared to its parent components. Presumably, the biocidal effects of the tested NMs can be attributed to the induction of oxidative stress, the release of metal ions and specific electrochemical interactions with the bacterial cells.     

Mixed-Metal MOF-74 Templated Catalysts for Efficient Carbon Dioxide Capture and Methanation

The vast chemical and structural tunability of metal–organic frameworks (MOFs) are beginning to be harnessed as functional supports for catalytic nanoparticles spanning a range of applications. However, a lack of straightforward methods for producing nanoparticle-encapsulated MOFs as efficient heterogeneous catalysts limits their usage. Herein, a mixed-metal MOF, NiMg-MOF-74, is utilized as a template to disperse small Ni nanoclusters throughout the parent MOF. By exploiting the difference in Ni O and Mg O coordination bond strength, Ni²⁺ is selectively reduced to form highly dispersed Ni nanoclusters constrained by the parent MOF pore diameter, while Mg²⁺ remains coordinated in the framework. By varying the ratio of Ni to Mg in the parent MOF, accessible surface area and crystallinity can be tuned upon thermal treatment, influencing CO₂ adsorption capacity and hydrogenation selectivity. The resulting Ni nanoclusters prove to be an active catalyst for CO₂ methanation and are examined using extended X-ray absorption fine structure and X-ray photoelectron spectroscopy. By preserving a segment of the Mg²⁺-containing MOF framework, the composite system retains a portion of its CO₂ adsorption capacity while continuing to deliver catalytic activity. The approach is thus critical for designing materials that can bridge the gap between carbon capture and CO₂ utilization.     

Tuning of ferrimagnetic nature and hyperfine interaction of Ni2+ doped cobalt ferrite nanoparticles for power transformer applications

Ferrites may contain single domain particles which gets converted into super-paramagnetic state near critical size. To explore the existence of these characteristic feature of ferrites, we have performed magnetization(M-H loop) and Mössbauer spectroscopic studies of Ni²⁺ substitution effect in Co_1-xNi_xFe₂O₄ (where x?=?0, 0.25, 0.5, 0.75 and 1) nanoparticles were fabricated by solution combustion route using mixture of carbamide and glucose as fuels for the first time. As prepared samples exhibit spinel cubic structure with lattice parameters which decreases linearly with increase in Ni²⁺ concentration. The M-H loops reveals that saturation magnetization(M_s), coercive field(H_c) remanence magnetization(M_r) and magnetron number(η_B) decreases significantly with increasing Ni²⁺ substitution. The variation of saturation magnetization has been explained on the basis of Neel's molecular field theory. The coercive field(H_c) is found strongly dependent on the concentration of Ni²⁺ and decrease of coercivity suggests that the particles have single domain and exhibits superparamagnetic behavior. The Mössbauer spectroscopy shows two ferrimagnetically relaxed Zeeman sextets distribution at room temperature. The dependence of Mössbauer parameters such as isomer shift, quadru pole splitting, line width and hyperfine magnetic field on Ni²⁺ concentration have been discussed. Hence our results suggest that synthesized materials are potential candidate for power transformer application.