Cyclosporin A toxicity on endothelial cells differentiated from induced pluripotent stem cells: Assembling an adverse outcome pathway.

Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically regarding vascular dysfunction. Its mode of action inducing endothelial cell toxicity is partially unclear, and a connection with an adverse outcome pathway (AOP) is not established yet.

Inactivation of MS-2 virus in water by rotational generator of hydraulic shock.

This study investigates the effect of hydraulic shock waves on inactivation of MS-2 bacteriophage, a norovirus surrogate. A falling circular jet of water spiked with the MS-2 (∼1000 PFU/mL) was repeatedly impacted by a rotating blade, resulting in occurrence of hydraulic shock waves within the liquid region adjacent to the impact. The proof-of-concept rotational generator of hydraulic shock treating 9 L of water spiked with viruses was able to achieve 3 logs reduction of viral plaque count within 80-100 liquid passes at moderate blade impact velocities (namely, 70 and 88 m/s) despite the water temperature not exceeding 40 °C and no detectible cavitation.

Modelling of chromatographic and electrophoretic behaviour of imidazoline and alpha adrenergic receptors ligands under different acid-base conditions.

Background And Purpose: The ligands of the imidazoline and α-adrenergic receptors are mainly imidazoline and guanidine derivatives, known as centrally-acting antihypertensives and compounds with potential use in various neurological disorders. The extent of their ionisation has a major influence on their behaviour in the different analytical systems. The main objective of this work was to compare the mechanism of chromatographic retention and electrophoretic mobility under acidic, neutral and basic conditions.

Shape-Selective Zeolites for Tandem CO Hydrogenation-Carbonylation Reactions.

The valorization of carbon dioxide as a C1 building block in C-C bond forming reactions is a critical link on the road to carbon-circular chemistry. Activation of this inert molecule through reduction with H to carbon monoxide in the reverse water-gas shift (RWGS) reaction can be followed by a wide spectrum of consecutive carbonylation reactions, but the RWGS is severely equilibrium limited at the moderate temperatures of carbonylations. Here we successfully reconcile both reactions in one pot, while avoiding incompatibilities through a zeolite-based compartmentalized approach.

Computational study of the HLTF ATPase remodeling domain suggests its activity on dsDNA and implications in damage tolerance.

The Helicase-Like Transcription Factor (HLTF) is member of the SWI/SNF-family of ATP dependent chromatin remodellers known primarily for maintaining genome stability. Biochemical and cellular assays support its multiple roles in DNA Damage Tolerance. However, the lack of sufficient structural data limits the comprehension of the molecular basis of its modes of action.

Diffusion and thermodynamic properties of lithium polysulfides in different solvents: a molecular dynamics approach.

Li-S batteries are promising alternatives due to their proven increased gravimetric capacity compared to Li-ion batteries. However, their development is hindered by many technical issues, one of the most challenging being the dissolution and shuttle of polysulfide species, which causes irreversible loss of cathode material leading to rapid capacity fading. Among the possible strategies to mitigate this effect, the choice of suitable solvents is easy to implement and has large room for improvement.

Deciphering the Two-Step Hydride Mechanism of Monoamine Oxidase Flavoenzymes.

The complete two-step hydride transfer mechanism of amine oxidation involved in the metabolism of monoamine neurotransmitters was scrutinized by DFT calculations. In living organisms, this process is catalyzed by monoamine oxidase enzymes. Herein, we focus on some intriguing aspects of the reaction that may have been previously noticed but have not been clarified to date.

Pivotal Role of Surface Terminations in MXene Thermodynamic Stability.

MXenes, i.e., two-dimensional transition metal carbides and nitrides, have been reported as promising materials for various applications, including energy storage, biomedicine, and electronics.

Computational Tools to Facilitate Early Warning of New Emerging Risk Chemicals.

Innovative tools suitable for chemical risk assessment are being developed in numerous domains, such as non-target chemical analysis, omics, and computational approaches. These methods will also be critical components in an efficient early warning system (EWS) for the identification of potentially hazardous chemicals. Much knowledge is missing for current use chemicals and thus computational methodologies complemented with fast screening techniques will be critical.

Navigational Signals for Insect and Slug Parasitic Nematodes: The Role of Ascorbate-Glutathione System and Volatiles Released by Insect-Damaged Sweet Pepper Roots.

This study of underground multitrophic communication, involving plant roots, insects, and parasitic nematodes, is an emerging field with significant implications for understanding plant-insect-nematode interactions. Our research investigated the impact of wireworm ( L. [Coleoptera: Elateridae]) infestations on the ascorbate-glutathione system in sweet pepper ( L.

Case specific: Addressing co-digestion of wastewater sludge, cheese whey and cow manure: Kinetic modeling.

The study investigated the methane production efficiency in a semi-continuous laboratory experiment with periodic feeding of wastewater sludge (WWS) as primary substrate and addition of whey (CW) and cow manure (CM). The short-term behavior of a real-scale anaerobic digester with WWS and the methane production improvements with different feeding mixtures of WWS, CW and CM were addressed. Gradual addition of CW to WWS (WWS:CW:CM = 70:20:0 to 70:55:0) increased the average daily methane production to 48.

Synthesis and Redox Activity of Polyenaminones for Sustainable Energy Storage Applications.

In the search for novel polymeric molecules that could be used as electroactive materials, seven novel polyenaminones were prepared in high yields by the transaminative polymerization of resorcinol-derived bis-enaminones with - and -phenylenediamine and with 2,5-diaminohydroquinone. The obtained polymers show very low solubility in organic solvents and absorb UV light and visible light at wavelengths below 500 nm. All the obtained polymeric products were tested for redox activity in a Li battery setup.

Hierarchically Porous Polyacetylene Networks: Adsorptive Photocatalysts for Efficient Bisphenol A Removal from Water.

In this article, we report a series of functionalized polyacetylene-type networks formed by chain-growth insertion coordination polymerization in high internal phase emulsions (HIPEs). All polymerized HIPEs (polyHIPEs) contain a hierarchically structured, 3D-interconnected porous framework consisting of a micro-, meso- and macropore system, resulting in exceptionally high specific surface areas (up to 1055 m·g) and total porosities of over 95%. The combination of π-conjugated and hierarchically porous structure in one material enabled the use of these polyacetylene polyHIPEs as adsorptive photocatalysts for the removal of chemical contaminants from water.

First dual inhibitors of human topoisomerase IIα and Hsp90 C-terminal domain inhibit the growth of Ewing sarcoma in vitro and in vivo.

Heat shock protein 90 (Hsp90) and topoisomerase IIα (TopoIIα) are members of the GHKL protein superfamily, both with clinically validated roles as anticancer drug targets. We report the discovery of the first class of dual inhibitors targeting the ATP-binding site of TopoIIα and the C-terminal domain of Hsp90, displaying potent cancer growth inhibition both in vitro and in vivo. Initially, a known TopoIIα inhibitor, compound 3, was shown to bind to the C-terminal domain of Hsp90, but not to its ATP-binding N-terminal domain.

Hiding in plain sight: Optimizing topoisomerase IIα inhibitors into Hsp90β selective binders.

Due to their impact on several oncogenic client proteins, the Hsp90 family of chaperones has been widely studied for the development of potential anticancer agents. Although several Hsp90 inhibitors have entered clinical trials, most were unsuccessful because they induced a heat shock response (HSR). This issue can be circumvented by using isoform-selective inhibitors, but the high similarity in the ATP-binding sites between the isoforms presents a challenge.

Fundamental and Practical Aspects of Break-In/Conditioning of Proton Exchange Membrane Fuel Cells.

Proton exchange membrane fuel cells (PEMFCs) have proven to be a promising power source for various applications ranging from portable devices to automotive and stationary power systems. The production of PEMFC involves numerous stages in the value chain, with each stage presenting unique challenges and opportunities to improve the overall performance and durability of the PEMFC stack. These include steps such as manufacturing the key components such as the platinum-based catalyst, processing these components into the membrane electrode assemblies (MEAs), and stacking the MEAs to ultimately produce a PEMFC stack.

Rhizobiome diversity of field-collected hyperaccumulating Noccaea sp.

Hyperaccumulating plants are able to (hyper)accumulate high concentrations of metal(loid)s in their above-ground tissues without any signs of toxicity. Studies on the root-associated microbiome have been previously conducted in relation to hyperaccumulators, yet much remains unknown about the interactions between hyperaccumulating hosts and their microbiomes, as well as the dynamics within these microbial communities. Here, we assess the impact of the plant host on shaping microbial communities of three naturally occurring populations of Noccaea species in Slovenia: Noccaea praecox and co-occurring N.

From computational models of the splicing code to regulatory mechanisms and therapeutic implications.

Since the discovery of RNA splicing and its role in gene expression, researchers have sought a set of rules, an algorithm or a computational model that could predict the splice isoforms, and their frequencies, produced from any transcribed gene in a specific cellular context. Over the past 30 years, these models have evolved from simple position weight matrices to deep-learning models capable of integrating sequence data across vast genomic distances. Most recently, new model architectures are moving the field closer to context-specific alternative splicing predictions, and advances in sequencing technologies are expanding the type of data that can be used to inform and interpret such models.

The influence of G-tract and loop length on the topological variability of putative five and six G-quartet DNA structures in the human genome.

Local variation of DNA structure and its dynamic nature play an essential role in the regulation of important biological processes. One of the most prominent noncanonical structures are G-quadruplexes, which form in vivo within guanine-rich regions and have been demonstrated to be involved in the regulation of transcription, translation and telomere maintenance. We provide an analysis of G-quadruplex formation in sequences with five and six guanine residues long G-tracts, which have emerged from the investigation of the gapless human genome and are associated with genes related to cancer and neurodegenerative diseases.

Complex Biophysical and Computational Analyses of G-Quadruplex Ligands: The Porphyrin Stacks Back.

G-quadruplexes (G4 s), as non-canonical DNA structures, attract a great deal of research interest in the molecular biology as well as in the material science fields. The use of small molecules as ligands for G-quadruplexes has emerged as a tool to regulate gene expression and telomeres maintenance. Meso-tetrakis-(N-methyl-4-pyridyl) porphyrin (TMPyP4) was shown as one of the first ligands for G-quadruplexes and it is still widely used.

4-Methoxypicolinic Acid -Oxide: One of the Shortest Hydrogen Bonds Known Characterized by Neutron Diffraction, Inelastic Neutron Scattering, Infrared Spectroscopy, and Periodic DFT Calculations.

The present work focuses on the case of an extremely short intramolecular O-H···O hydrogen bond (H-bond) found in 4-methoxypicolinic acid -oxide (MPANO). The donor···acceptor separation of 2.403 Å makes the H-bond in MPANO one of the shortest H-bonds known.

Entangling roles of cholesterol-dependent interaction and cholesterol-mediated lipid phase heterogeneity in regulating listeriolysin O pore-formation.

Cholesterol-dependent cytolysins (CDCs) are the distinct class of β-barrel pore-forming toxins (β-PFTs) that attack eukaryotic cell membranes, and form large, oligomeric, transmembrane β-barrel pores. Listeriolysin O (LLO) is a prominent member in the CDC family. As documented for the other CDCs, membrane cholesterol is essential for the pore-forming functionality of LLO.

Predictive modeling of colorectal cancer using exhaustive analysis of microbiome information layers available from public metagenomic data.

This study aimed to compare the microbiome profiles of patients with colorectal cancer (CRC,  = 380) and colorectal adenomas (CRA,  = 110) against generally healthy participants ( = 2,461) from various studies. The overarching objective was to conduct a real-life experiment and develop a robust machine learning model applicable to the general population. A total of 2,951 stool samples underwent a comprehensive analysis using the in-house MetaBakery pipeline.