Phe-Gly motifs drive fibrillization of TDP-43’s prion-like domain condensates

Transactive response DNA-binding Protein of 43 kDa (TDP-43) assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g., muscle regeneration versus neurodegeneration). The link between condensates and fibrils remains unclear, just as the factors controlling conformational transitions within these aggregate species: Salt- or RNA-induced droplets may evolve into fibrils or remain in the droplet form, suggesting distinct end point species of different aggregation pathways. Using microscopy and NMR methods, we unexpectedly observed in vitro droplet formation in the absence of salts or RNAs and provided visual evidence for fibrillization at the droplet surface/solvent interface but not the droplet interior. Our NMR analyses unambiguously uncovered a distinct amyloid conformation in which Phe-Gly motifs are key elements of the reconstituted fibril form, suggesting a pivotal role for these residues in creating the fibril core. This contrasts the minor participation of Phe-Gly motifs in initiation of the droplet form. Our results point to an intrinsic (i.e., non-induced) aggregation pathway that may exist over a broad range of conditions and illustrate structural features that distinguishes between aggregate forms.

Two-dimensional MOF-based Liquid Marbles: Surface Energy Calculations and Efficient Oil-Water Separation Using a ZIF-9-III@PVDF Membrane

Superhydrophobic MOF-nanosheets assembled on the outside of an aqueous droplet form ‘liquid marbles’. A facile mechanochemical-based synthesis followed by ultrasonication was used to prepare two-dimensional superhydrophobic-oleophilic MOF nanosheets of a...

Spatial Modeling of Maximum Capacity Values of Irrecoverable Rainfall Retention by Forests in a Small Watershed

When performing hydrologic calculations, the actual amount of rain precipitation falling under the tree canopies of the taiga zone is one of the most important factors in forming and estimating rainfall runoff. This is due to the fact that only a portion of rainfall reaching the soil through the forest canopy takes part in forming river runoff. At present, there is no unanimity on methods of estimating rainfall retention by the canopies of different tree species in various natural geographical zones. The existing estimation methods rely on empirical observations of net and gross rainfall rather than on the results of physical modeling of moisture on leaf surfaces in droplet form. The disadvantages of the existing methods mean that it is not possible to make a spatial estimation of rainfall captured by canopies. The purpose of this study was to map the maximum rainfall interception capacity for a small forest watershed. The authors were able to solve the following problems: (1) In situ modeling of specific water retention in droplet form on leaf surfaces of tree species of the experimental watershed in the middle taiga subzone was carried out and the specific water retention per unit leaf area was determined. Such experiments have never been conducted previously. (2) Indirect methods of estimating the leaf surface area of tree plants depending on the amount of phytomass, age and height of tree stands were developed. (3) Mapping of tree stand characteristics (such as species composition, height, canopy cover) were performed, and together with the specific rainfall interception capacity, which was determined during experiments, provided the basis for a map of maximum rainfall retention capacity by canopies, i.e., a spatial image of irrecoverable rainfall losses was obtained. Rainfall is retained on a canopy in droplet form (droplet size varies from 10.6 to 18.6 mg). Specific water retention (mass per unit leaf surface area) is determined by the leaf (needle) roughness. The overall droplet retention on canopies is determined by leaf surface area and precipitation intensity. The maximum mass of the rainfall retained on the canopies of individual deciduous trees reaches 77 kg, (3.0–4.0 mm per canopy projection area) and that of coniferous trees ranges from 24.8 to 58.0 kg (1.9 to 5.9 mm). Understanding rainfall loss values in hydrology is of key importance in distributed models of rainfall flooding. Taking into account rainfall losses due to canopy interception makes it possible to reduce the margin of error in calculations of maximum rainfall flood loss from 126% to 25%.

Phe-Gly motifs drive fibrillization of TDP-43’s prion-like domain droplets

TDP-43 assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g. muscle regeneration versus neurodegeneration). The link between condensates and fibrils remains unclear, just as the factors controlling conformational transitions within these aggregate species: salt- or RNA-induced droplets may evolve into fibrils or remain in the droplet form, suggesting distinct endpoint species of different aggregation pathways. Using microscopy and NMR methods, we unexpectedly observed in vitro droplet formation in the absence of salts or RNAs, and provided visual evidence for fibrillization at the droplet surface/solvent interface but not the droplet interior. Our NMR analyses unambiguously uncovered a distinct amyloid conformation in which Phe-Gly motifs are key elements of the reconstituted fibril form, suggesting a pivotal role for these residues in creating the fibril core. This contrasts the minor participation of Phe-Gly motifs in initiation of the droplet form. Our results point to an intrinsic (i.e., non-induced) aggregation pathway that may exist over a broad range of conditions, and illustrate structural features that distinguishes between aggregate forms.

THE BACTERICIDAL ACTION OF PROPYLENE GLYCOL VAPOR ON MICROORGANISMS SUSPENDED IN AIR. I

It has been found that propylene glycol vapor dispersed into the air of an enclosed space produces a marked and rapid bactericidal effect on microorganisms introduced into such an atmosphere in droplet form. Concentrations of 1 gm. of propylene glycol vapor in two to four million cc. of air produced immediate and complete sterilization of air into which pneumococci, streptococci, staphylococci, H. influenzae, and other microorganisms as well as influenza virus had been sprayed. With lesser concentrations of propylene glycol, rapid and marked reduction in the number of air-borne bacteria occurred, but complete sterilization of the air required a certain interval of time. Pronounced effects on both pneumococci and hemolytic streptococci were observed when concentrations as low as 1 gm. of glycol to fifty million cc. of air were employed. Numerous control tests showed that failure of the glycol-treated microorganisms to grow on the agar plates was due to actual death of the bacteria. The means by which propylene glycol vapor produces its effect on droplet-borne bacteria is discussed and data relating the bactericidal properties of propylene glycol in vitro to the lethal action of its vapor is presented. Atmospheres containing propylene glycol vapor are invisible, odorless, and non-irritating. This glycol is essentially non-toxic when given orally and intravenously. Tests on possible deleterious effects of breathing propylene glycol containing atmospheres over long periods of time are being carried out.