Spatial Structures of Fibrillar Proteins

The protein molecules are considerate in the space of the highest dimension with a change in dimension with demand at the conformation of the molecules. It was shown that the widespread quasi-plane model of the Pouling protein structure do not reflect and even contradict the spatial structures of the protein in various conformations. It was found that the linear structures and folded structures of the protein in space of the highest dimension have translational symmetry. The elementary elements of protein translational symmetry were determined, their dimensions were calculated (9 for the linear structures and 23 for folded structures).

Autonomous epithelial folding induced by an intracellular mechano–polarity feedback loop

Epithelial tissues form folded structures during embryonic development and organogenesis. Whereas substantial efforts have been devoted to identifying mechanical and biochemical mechanisms that induce folding, whether and how their interplay synergistically shapes epithelial folds remains poorly understood. Here we propose a mechano–biochemical model for dorsal fold formation in the early Drosophila embryo, an epithelial folding event induced by shifts of cell polarity. Based on experimentally observed apical domain homeostasis, we couple cell mechanics to polarity and find that mechanical changes following the initial polarity shifts alter cell geometry, which in turn influences the reaction-diffusion of polarity proteins, thus forming a feedback loop between cell mechanics and polarity. This model can induce spontaneous fold formation in silico, recapitulate polarity and shape changes observed in vivo, and confer robustness to tissue shape change against small fluctuations in mechanics and polarity. These findings reveal emergent properties of a developing epithelium under control of intracellular mechano–polarity coupling.

Compression and Stretching of Confined Linear and Ring Polymers by Applying Force

We use Langevin dynamics to study the deformations of linear and ring polymers in different confinements by applying compression and stretching forces on their two sides. Our results show that the compression deformations are the results of an interplay among of polymer rigidity, degree of confinement, and force applied. When the applied force is beyond the threshold required for the buckling transition, the semiflexible chain under the strong confinement firstly buckles; then comes helical deformation. However, under the same force loading, the semiflexible chain under the weaker confinement exhibits buckling instability and shrinks from the folded ends/sides until it becomes three-folded structures. This happens because the strong confinement not only strongly reduces the buckling wavelength, but also increases the critical buckling force threshold. For the weakly confined polymers, in compression process, the flexible linear polymer collapses into condensed states under a small external force, whereas the ring polymer only shows slight shrinkage, due to the excluded volume interactions of two strands in the crowded states. These results are essential for understanding the deformations of the ring biomacromolecules and polymer chains in mechanical compression or driven transport.

THROMBOSE-FIBROUS COMPLICATIONS OF SYSTEMIC ENDOTHELIUM DAMAGE AT COVID-19

The analysis of literature data and our own research of lungs tissues of the persons who died owing to COVID-19 caused fibrosis testify to participation in this pathology of a cascade of disturbances of molecular and cellular levels. Viral damage to endothelial cells causes systemic damage to the vascular glycocalyx, which loses its clotting properties and releases significant amounts of blood clotting factors. The fibrin clot formed under such conditions is characterized by resistance to fibrinolysis and locally blocks blood vessels with the systemic development of endogenous intoxication. Destabilized proteins of the latter form micro- and nano-sized aggregates with a significant content of β-folded structures. This contributes to the increase of fibrin resistance to the proteolytic action of plasmin, causes the development of fibrosis of the tissues affected in this way, and leads to the failure of the functions of the relevant organs.

RNA G-quadruplex structures control ribosomal protein production

Four-stranded G-quadruplex (G4) structures form from guanine-rich tracts, but the extent of their formation in cellular RNA and details of their role in RNA biology remain poorly defined. Herein, we first delineate the presence of endogenous RNA G4s in the human cytoplasmic transcriptome via the binding sites of G4-interacting proteins, DDX3X (previously published), DHX36 and GRSF1. We demonstrate that a sub-population of these RNA G4s are reliably detected as folded structures in cross-linked cellular lysates using the G4 structure-specific antibody BG4. The 5′ UTRs of protein coding mRNAs show significant enrichment in folded RNA G4s, particularly those for ribosomal proteins. Mutational disruption of G4s in ribosomal protein UTRs alleviates translation in vitro, whereas in cells, depletion of G4-resolving helicases or treatment with G4-stabilising small molecules inhibit the translation of ribosomal protein mRNAs. Our findings point to a common mode for translational co-regulation mediated by G4 structures. The results reveal a potential avenue for therapeutic intervention in diseases with dysregulated translation, such as cancer.

Macroscopic imprints of ductile deformation

The fundamentals of structural geology are presented, namely, folds, planar structures (cleavage or schistosity, foliation) and linear ones (lineations), regarded as emblematic for geologists. Ductile imprints of folds, affecting stratified formations, combined with brittle imprints, often remain modest in terms of strain intensity. Folding is essentially inhomogeneous and often results from the buckling (bending) of the layers (or stratification) as a consequence of layer parallel compression. Folded structures are frequently accompanied by fractures. Hence they may be classified as brittle–ductile. They are mostly encountered at low depths and constitute the upper structural level of the Earth’s crust. Ductile deformation sensu stricto appears at the lower structural level. The macroscopic aspects of ductile deformations and their implications will be examined. The principal operating mechanism, crystalline plasticity, represents the mechanical aspect of deformation, sometime assisted by chemical aspects (pressure-solution). While homogeneous deformation constitutes our principal concern, heterogeneous deformation is often present, particularly when examined at fine scales. At low shear strain (γ‎ < 0.7, or θ‎ ~35°, equivalent to ~30% shortening), plastic deformation generally leads to a planar and a linear anisotropy strengthening with increasing deformation. At higher shear strain, any pre-existing planar structure becomes so stretched that it cannot be recognized. The new structure may be purely planar, purely linear or plano-linear. Lattice fabrics, appearing in rocks subjected to plastic deformation and resulting from deformation mechanisms at the grain-scale, are examined in detail in Chapter 6.

Finite Element Analysis and Thick-Panel Clash Behaviour of Steel Fold-Lines

The structural and mechanical behaviours of most origami-inspired or folded structures is strongly dependent upon the mechanical behaviours of their constituent crease lines. Characterisation of the rotational behaviours of the steel hinges is therefore a critical step in the analysis of origami-inspired steel structures. This paper will present a numerical modelling approach for simulating the rotational response of digitally-fabricated steel hinges, over a large rotation range from 0° up to 170°. Numerical response predictions are verified against published experimental results, over a range of sheet thicknesses and fold line parameters. Models are then used to give insight into observed thick-panel clash behaviours and fold-line localised strap mechanics. The developed numerical modelling procedure provides a convenient analysis method for rapid prediction of steel hinge behaviour.

Computational and experimental assessment of backbone templates for computational protein design

Computational protein design has taken big strides over the recent years, however, the tools available are still not at a state where a sequence can be designed to fold into a given protein structure at will and with high probability. We have here applied a recent release of Rosetta Design to redesign a set of structurally very similar proteins belonging to the Thioredoxin fold. We determined design success using a combination of a genetic screening tool to assay folding/stability in E. coli and selecting the best hits from this for further biochemical characterization. We have previously used this set of template proteins for redesign and found that success was highly dependent on template structure, a trait which was also found in this study. Nevertheless, state of the art design software is now able to predict the best template, most likely due to the introduction of the cart_bonded energy term. The template that led to the greatest fraction of successful designs was the same (a Thioredoxin from spinach) as that identified in our previous study. Our previously described redesign of Thioredoxin, which also used the spinach protein as template, however also performed well. In the present study, both these templates yielded proteins with compact folded structures, and enforces the conclusion that any design project must carefully consider different design templates. Fortunately, selecting designs using the cart_bonded energy term appears to correctly identify such templates.