Space Analogs and Behavioral Health Performance Research review and recommendations checklist from ESA Topical Team.

Space analog research has increased over the last few years with new analogs appearing every year. Research in this field is very important for future real mission planning, selection and training of astronauts. Analog environments offer specific characteristics that resemble to some extent the environment of a real space mission.

Biomolecular simulations at the exascale: From drug design to organelles and beyond.

The rapid advancement in computational power available for research offers to bring not only quantitative improvements, but also qualitative changes in the field of biomolecular simulation. Here, we review the state of biomolecular dynamics simulations at the threshold to exascale resources becoming available. Both developments in parallel and distributed computing will be discussed, providing a perspective on the state of the art of both.

Selectivity filter mutations shift ion permeation mechanism in potassium channels.

Potassium (K) channels combine high conductance with high ion selectivity. To explain this efficiency, two molecular mechanisms have been proposed. The "direct knock-on" mechanism is defined by water-free K permeation and formation of direct ion-ion contacts in the highly conserved selectivity filter (SF).

Measuring digital transformation stress at the workplace-Development and validation of the digital transformation stress scale.

Despite the unquestionable advantages of digital transformation (DT) in organizations, the very process of DT could have an impact on the level of stress of the employees. The negative effects of the digital transformation process can be observed during the implementation of information and communication technologies (ICT) solutions. They are further enhanced by the effects of COVID-19 pandemic, as digital transformation has accelerated to allow for remote work.

Interactions between selectivity filter and pore helix control filter gating in the MthK channel.

K+ channel activity can be limited by C-type inactivation, which is likely initiated in part by dissociation of K+ ions from the selectivity filter and modulated by the side chains that surround it. While crystallographic and computational studies have linked inactivation to a "collapsed" selectivity filter conformation in the KcsA channel, the structural basis for selectivity filter gating in other K+ channels is less clear. Here, we combined electrophysiological recordings with molecular dynamics simulations, to study selectivity filter gating in the model potassium channel MthK and its V55E mutant (analogous to KcsA E71) in the pore-helix.

Spin-Resolved Band Structure of Hoffman Clathrate [Fe(pz)Pt(CN)] as an Essential Tool to Predict Optical Spectra of Metal-Organic Frameworks.

Paramount spin-crossover properties of the 3D-Hoffman metalorganic framework (MOF) [Fe(pz)Pt(CN)] are generally described on the basis of the ligand field theory, which provides adequate insight into theoretical and simulation analysis of spintronic complexes. However, the ligand field approximation does not take into account the 3D periodicity of the actual complex lattice and surface effects and therefore cannot predict a full-scale periodic structure without utilizing more advanced methods. Therefore, in this paper, the electronic properties of the exemplar MOF were analyzed from the band structure perspective in low-spin (LS) and high-spin (HS) states.

Dipeptide Extract Modulates the Oxi-Antioxidant Response to Intense Physical Exercise.

Exposure to intense physical exercise increases reactive oxygen and nitrogen species production. The process can be modulated by dipeptide bioavailability with antioxidant scavenger properties. The effects of dipeptide intake in combination with physical exercise on the oxi-antioxidant response were examined in a randomized and placebo-controlled trial.

Direct Detection of Bound Ammonium Ions in the Selectivity Filter of Ion Channels by Solid-State NMR.

The flow of ions across cell membranes facilitated by ion channels is an important function for all living cells. Despite the huge amount of structural data provided by crystallography, elucidating the exact interactions between the selectivity filter atoms and bound ions is challenging. Here, we detect bound N-labeled ammonium ions as a mimic for potassium ions in ion channels using solid-state NMR under near-native conditions.

Thin Films of Nanocrystalline Fe(pz)[Pt(CN)] Deposited by Resonant Matrix-Assisted Pulsed Laser Evaporation.

Prior studies of the thin film deposition of the metal-organic compound of Fe(pz)Pt[CN] (pz = pyrazine) using the matrix-assisted pulsed laser evaporation (MAPLE) method, provided evidence for laser-induced decomposition of the molecular structure resulting in a significant downshift of the spin transition temperature. In this work we report new results obtained with a tunable pulsed laser, adjusted to water resonance absorption band with a maximum at 3080 nm, instead of 1064 nm laser, to overcome limitations related to laser-target interactions. Using this approach, we obtain uniform and functional thin films of Fe(pz)Pt[CN] nanoparticles with an average thickness of 135 nm on Si and/or glass substrates.

Characteristics of Reconstituted Collagen Fibers from Chicken Keel Cartilage Depends on Salt Type for Removal of Proteoglycans.

The aim of the presented research was to obtain reconstituted atelocollagen fibers after extraction from poultry cartilage using the pepsin-acidic method in order to remove telopeptides from the tropocollagen. Firstly, we examined the extraction of collagen from the cartilage extracellular matrix (ECM) after proteoglycans (PG) had been removed by the action of salts, i.e.

Structural plasticity of the selectivity filter in a nonselective ion channel.

The sodium potassium ion channel (NaK) is a nonselective ion channel that conducts both sodium and potassium across the cellular membrane. A new crystallographic structure of NaK reveals conformational differences in the residues that make up the selectivity filter between the four subunits that form the ion channel and the inner helix of the ion channel. The crystallographic structure also identifies a side-entry, ion-conduction pathway for Na permeation that is unique to NaK.

The Persistent Question of Potassium Channel Permeation Mechanisms.

Potassium channels play critical roles in many physiological processes, providing a selective permeation route for K ions in and out of a cell, by employing a carefully designed selectivity filter, evolutionarily conserved from viruses to mammals. The structure of the selectivity filter was determined at atomic resolution by x-ray crystallography, showing a tight coordination of desolvated K ions by the channel. However, the molecular mechanism of K ions permeation through potassium channels remains unclear, with structural, functional and computational studies often providing conflicting data and interpretations.

The Influence of Oxidative Stress on Serum Albumin Structure as a Carrier of Selected Diazaphenothiazine with Potential Anticancer Activity.

Albumin is one of the most important proteins in human blood. Among its multiple functions, drug binding is crucial in terms of drug distribution in human body. This protein undergoes many modifications that are certain to influence protein activity and affect its structure.

Antioxidative Characteristics of Chicken Breast Meat and Blood after Diet Supplementation with Carnosine, L-histidine, and β-alanine.

The objective of the study was to test the effect of diets supplemented with β-alanine, L-histidine, and carnosine on the histidine dipeptide content and the antioxidative status of chicken breast muscles and blood. One-day-old Hubbard Flex male chickens were assigned to five treatments: control diet (C) and control diet supplemented with 0.18% L-histidine (ExpH), 0.

Polycation-Anionic Lipid Membrane Interactions.

Natural or synthetic polycations are used as biocides or as drug/gene carriers. Understanding the interactions between these macromolecules and cell membranes at the molecular level is therefore of great importance for the design of effective polymer biocides or biocompatible polycation-based delivery systems. Until now, details of the processes at the interface between polycations and biological systems have not been fully recognized.

The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation.

Protein dynamics are essential to function. One example of this is the various gating mechanisms within ion channels, which are transmembrane proteins that act as gateways into the cell. Typical ion channels switch between an open and closed state via a conformational transition which is often triggered by an external stimulus, such as ligand binding or pH and voltage differences.

A β-barrel for oil transport through lipid membranes: Dynamic NMR structures of AlkL.

The protein AlkL is known to increase permeability of the outer membrane of bacteria for hydrophobic molecules, yet the mechanism of transport has not been determined. Differing crystal and NMR structures of homologous proteins resulted in a controversy regarding the degree of structure and the role of long extracellular loops. Here we solve this controversy by determining the de novo NMR structure in near-native lipid bilayers, and by accessing structural dynamics relevant to hydrophobic substrate permeation through molecular-dynamics simulations and by characteristic NMR relaxation parameters.

Molecular mechanism of a potassium channel gating through activation gate-selectivity filter coupling.

Potassium channels are presumed to have two allosterically coupled gates, the activation gate and the selectivity filter gate, that control channel opening, closing, and inactivation. However, the molecular mechanism of how these gates regulate Kion flow through the channel remains poorly understood. An activation process, occurring at the selectivity filter, has been recently proposed for several potassium channels.

The conduction pathway of potassium channels is water free under physiological conditions.

Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a "water-mediated" knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a "direct" knock-on mechanism where ions are in direct contact.

Molecular Mechanism of Polycation-Induced Pore Formation in Biomembranes.

Polycations are an attractive class of macromolecules with promising applications as drug/gene carriers and biocides. The chemical structure and concentration of a polycation determine its interaction with cellular membranes and, hence, are crucial parameters for designing efficient nontoxic polycations. However, the interaction of polycations with biomembranes at the molecular level and the corresponding free-energy landscape is not well understood.

Conotoxin κM-RIIIJ, a tool targeting asymmetric heteromeric K1 channels.

The vast complexity of native heteromeric K channels is largely unexplored. Defining the composition and subunit arrangement of individual subunits in native heteromeric K channels and establishing their physiological roles is experimentally challenging. Here we systematically explored this "zone of ignorance" in molecular neuroscience.

K binding and proton redistribution in the EP state of the H, K-ATPase.

The H, K-ATPase (HKA) uses ATP to pump protons into the gastric lumen against a million-fold proton concentration gradient while counter-transporting K from the lumen. The mechanism of release of a proton into a highly acidic stomach environment, and the subsequent binding of a K ion necessitates a network of protonable residues and dynamically changing protonation states in the cation binding pocket dominated by five acidic amino acid residues E343, E795, E820, D824, and D942. We perform molecular dynamics simulations of spontaneous K binding to all possible protonation combinations of the acidic amino acids and carry out free energy calculations to determine the optimal protonation state of the luminal-open EP state of the pump which is ready to bind luminal K.

Direct knock-on of desolvated ions governs strict ion selectivity in K channels.

The seeming contradiction that K channels conduct K ions at maximal throughput rates while not permeating slightly smaller Na ions has perplexed scientists for decades. Although numerous models have addressed selective permeation in K channels, the combination of conduction efficiency and ion selectivity has not yet been linked through a unified functional model. Here, we investigate the mechanism of ion selectivity through atomistic simulations totalling more than 400 μs in length, which include over 7,000 permeation events.

In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways.

The ryanodine receptor 1 is a large calcium ion channel found in mammalian skeletal muscle. The ion channel gained a lot of attention recently, after multiple independent authors published near-atomic cryo electron microscopy data. Taking advantage of the unprecedented quality of structural data, we performed molecular dynamics simulations on the entire ion channel as well as on a reduced model.