Intrinsically disordered proteins and biomolecular condensates as drug targets

Intrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly dynamic assemblies, generally known as biomolecular condensates that define environments that can be quite different from the solutions surrounding them. In what follows, we review key recent findings in this area and show how biomolecular condensation can offer opportunities for modulating the activities of intrinsically disordered targets.     

Extremely Low Frequency Magnetic Fields Suppress the Reduction of Germination Rate of Arabidopsis thaliana Seeds Kept in Saturated Humidity

The effects of an extremely low frequency magnetic field (ELFMF) on the germination of plant seeds were examined. The decrease in the germination activity of the seeds of Arabidopsis thaliana WS kept in saturated humidity and high temperature (37°C) was suppressed by the exposure to a 400 mT ELFMF.     

Analysis of Water Sorption Isotherms of Superabsorbent Polymers by Solution Thermodynamics

Water sorption isotherms of superabsorbent polymers were measured, and their affinity for water was evaluated by solution thermodynamics. The results provide basic data for the functional packaging of food to control the water content of food during its transportation or storage. Water activity above 0.9 was measured by adding a specific amount of water to the samples, while that below 0.9 was measured with apparatus for evaluating water sorption isotherms. Thus, water sorption isotherms for superabsorbent polymers were obtained up to a water activity of approximately 0.98. The amount of water sorbed by the superabsorbent polymers was influenced by the type of functional groups in the polymers, and not by the degree of cross-linking in the polymers. The integral Gibbs free energy, which is the most suitable parameter for evaluating the affinity of a material for water, was evaluated from the water sorption isotherms by using solution thermodynamics.     

The phycobilisome core-membrane linkers from Synechocystis sp. PCC 6803 and red-algae assemble in the same topology

The phycobilisomes (PBSs) of cyanobacteria and red-algae are unique megadaltons light-harvesting protein-pigment complexes that utilize bilin derivatives for light absorption and energy transfer. Recently, the high-resolution molecular structures of red-algal PBSs revealed how the multi-domain core-membrane linker (L_CM) specifically organizes the allophycocyanin subunits in the PBS’s core. But, the topology of L_CM in these structures was different than that suggested for cyanobacterial PBSs based on lower-resolution structures. Particularly, the model for cyanobacteria assumed that the Arm2 domain of L_CM connects the two basal allophycocyanin cylinders, whereas the red-algal PBS structures revealed that Arm2 is partly buried in the core of one basal cylinder and connects it to the top cylinder. Here, we show by biochemical analysis of mutations in the apcE gene that encodes L_CM, that the cyanobacterial and red-algal L_CM topologies are actually the same. We found that removing the top cylinder linker domain in L_CM splits the PBS core longitudinally into two separate basal cylinders. Deleting either all or part of the helix-loop-helix domain at the N-terminal end of Arm2, disassembled the basal cylinders and resulted in degradation of the part containing the terminal emitter, ApcD. Deleting the following 30 amino-acids loop severely affected the assembly of the basal cylinders, but further deletion of the amino-acids at the C-terminal half of Arm2 had only minor effects on this assembly. Altogether, the biochemical data are consistent with the red-algal L_CM topology, suggesting that the PBS cores in cyanobacteria and red-algae assemble in the same way.     

Rational Design of Hybrid Nanostructures for Advanced Photocatalysis

Nanocatalysis has been a growing field over the past few decades with significant developments in understanding the surface properties of nanocatalysts. With recent advances in synthetic methods, size, shape and composition of the nanoparticles can be controlled in a well defined manner which facilitates achieving selective reaction products in multipath reactions. Nanoparticles with specific exposed crystal facets can have different reactivity than other facets for reaction intermediates, which favours selective pathways during the course of reaction. Heterogeneous catalysts have been studied extensively; nano‐sized metal particles are absorbed on mesoporus supports, facilitating access to the large surface area of the nanoparticles and hence exposure of more catalytic sites. Photocatalysis is attractive area of catalysis, in which photoinduced charge carriers are used for a variety of catalytic applications. More interestingly, clean and renewable liquid fuels energy sources such as hydrogen and methyl alcohol can be generated using photocatalysts through water splitting and CO₂ reduction, respectively. Herein, we highlight the progress of nanocatalysis through metal, bimetallic nanoparticle, metal‐semiconductor hybrid nanostructures and oxide nanoparticles for various reactions.     

Energy and Carbon Management Systems

This article examines an important class of information system that serves as the foundation for corporate energy and greenhouse gas (GHG) accounting: energy and carbon management systems (ECMS). Investors, regulators, customers, and employees increasingly demand that organizations provide information about their organizational energy use and GHG emissions. However, there is little transparency about how organizations use ECMS to meet such demands. To shed light on ECMS implementation and application, we collected extensive qualitative interview data from two service‐sector organizations: one that uses a spreadsheet‐based ECMS and another that implemented an ECMS provided by a third‐party vendor. Our analysis of collected data revealed numerous challenges in the areas of business processes, managerial capabilities, data capture and integration, and data quality. Though our study is built on only two organizations and requires confirmation in large‐sample surveys, we provide several recommendations for organizations regarding ECMS. We also provide suggestions for future studies to build on our tentative results.     

Effects of Sinusoidal 0.5 mT Magnetic Field on Leukocyte Adherence Inhibition

Exposure of T lymphocytes to an external 50 Hz and 0.5 mT magnetic field was investigated in vitro using leukocyte adherence inhibition (LAI) assay which is a measure of cell-mediated immunity. Adherence of T lymphocytes taken from healthy humans and from cancer patients before and after medical treatment is enhanced after 1 h exposure to the magnetic field. The experimental findings for the magnetic field 0.5 mT are compared with published data for 1 and 10 mT. The results are consistent with suggestions of magnetic field effects on immune function in humans.     

An efficient technique for the prediction of solvent-dependent morphology: the COSMIC method

We have developed a method of calculating the solvation energy of a surface based on an implicit solvent model. This new model called COSMIC, is an extension of the established COSMO solvation approach and allows the technique to be applied to systems of any periodicity from finite molecules, through polymers and surfaces, to cavities of water within a bulk unit cell. As well as extending the scope of the COSMO technique, it also improves the numerical stability through removal of a number of discontinuities in the potential energy surface. The COSMIC model has been applied to barium sulfate, where it was found to produce similar surface energies and configurations to the much more computationally expensive explicit molecular dynamics simulations. The calculated solvated morphology of barium sulfate was found to differ significantly to that calculated in vacuum with a reduced number of faces present.