Structural transitions in the GTP cap visualized by cryo-electron microscopy of catalytically inactive microtubules

Microtubules (MTs) are polymers of αβ-tubulin heterodimers that stochastically switch between growth and shrinkage phases. This dynamic instability is critically important for MT function. It is believed that GTP hydrolysis within the MT lattice is accompanied by destabilizing conformational changes and that MT stability depends on a transiently existing GTP cap at the growing MT end. Here, we use cryo-electron microscopy and total internal reflection fluorescence microscopy of GTP hydrolysis–deficient MTs assembled from mutant recombinant human tubulin to investigate the structure of a GTP-bound MT lattice. We find that the GTP-MT lattice of two mutants in which the catalytically active glutamate in α-tubulin was substituted by inactive amino acids (E254A and E254N) is remarkably plastic. Undecorated E254A and E254N MTs with 13 protofilaments both have an expanded lattice but display opposite protofilament twists, making these lattices distinct from the compacted lattice of wild-type GDP-MTs. End-binding proteins of the EB family have the ability to compact both mutant GTP lattices and to stabilize a negative twist, suggesting that they promote this transition also in the GTP cap of wild-type MTs, thereby contributing to the maturation of the MT structure. We also find that the MT seam appears to be stabilized in mutant GTP-MTs and destabilized in GDP-MTs, supporting the proposal that the seam plays an important role in MT stability. Together, these structures of catalytically inactive MTs add mechanistic insight into the GTP state of MTs, the stability of the GTP- and GDP-bound lattice, and our overall understanding of MT dynamic instability.

Reinvestigation on Assessing the Stability of Mullagulov Tested Steel Rods under Follower Forces

Dynamic instability is an interesting topic in the mechanics of elastic structures. Though the subject has been formed by many analytical, numerical, and experimental investigations, it has many issues, as evidenced from the critical overview of Elishakoff. Furthermore, the controversial articles of Koiter and Sugiyama on unrealistic and realistic follower forces demand experimental verification. Mullagulov has proposed a device for creating the follower forces and tested steel rods under compression. This paper highlights the experimentation of Mullagulov and his observations briefly to examine the influence of material properties on the stability load estimations and to confirm the practical realization of follower forces.

Simulation Modeling of a Ship Propulsion System in Wavesfor Control Purposes

The article deals with a simulation approach to the representation of the ship motions in waves, interacting with the propulsion system behavior (diesel engine and propeller). The final goal is the development of a simulator, as complete as possible, that allows the analysis of the main engine thermodynamics in different sea conditions, also in the unfavorable event of dynamic instability of the hull, and the correct management of the other propulsion components. This latter aspect is particularly interesting in some of the last new energy solutions for decarbonization of ships, concerning, for example, auxiliary electric motors, powered by batteries, to support the traditional diesel-mechanical propulsion (especially in heavy weather conditions). From this point of view, a proper analysis of the engine dynamic performance, affected by particular sea states, is fundamental for a smart management and control of shaft generators/auxiliary electric motors, batteries, etc. To this end, the work presents and highlights the main features of a ship simulator, suitable for the study of the new propulsion solutions that are emerging in maritime transport. Some representative results will point out the complex non-linear behavior of the propulsion plant in waves. Moreover, a parametric roll scenario will be investigated, in order to highlight the capability of the conceived simulator in modeling the effects of the dynamic instability of the hull on the propulsion plant.

Upper Cervical Compression Myelopathy Caused by the Retro-Odontoid Pseudotumor With Degenerative Osteoarthritis and Calcium Pyrophosphate Dihydrate Disease: A Case Report and Literature Review

The retro-odontoid pseudotumor is often concurrent with atlantoaxial subluxation (AAS). Therefore, the pseudotumor is relatively common in rheumatoid arthritis (RA) but rare in primary osteoarthritis (OA). This is a case report of an elderly male patient suffering from neck pain and compression myelopathy caused by the craniocervical pseudotumor with OA but without atlantoaxial instability. He had long-lasting peripheral and spinal pain treated by nonsteroidal anti-inflammatory drugs. Imaging found upper cervical spondylosis without AAS or dynamic instability but with periodontoid calcifications and ossifications, suggesting calcium pyrophosphate dihydrate (CPPD) crystal deposition. Based on a comprehensive literature search and review, CPPD disease around the atlantodental joint is a possible contributor to secondary OA development and retro-odontoid pannus formation through chronic inflammation, which can be enough severe to induce compression myelopathy in non-RA patients without AAS. The global increase in the aged population advises caution regarding more prevalent upper cervical spine disorders associated with OA and CPPD.

SSNA1 stabilizes dynamic microtubules and detects microtubule damage

Sjögren's Syndrome Nuclear Autoantigen 1 (SSNA1/NA14) is a microtubule-associated protein with important functions in cilia, dividing cells and developing neurons. However, the direct effects of SSNA1 on microtubules are not known. We employed in vitro reconstitution with purified proteins and TIRF microscopy to investigate the activity of human SSNA1 on dynamic microtubule ends and lattices. Our results show that SSNA1 modulates all parameters of microtubule dynamic instability - slowing down the rates of growth, shrinkage and catastrophe, and promoting rescue. We find that SSNA1 forms stretches along growing microtubule ends and binds cooperatively to the microtubule lattice. Furthermore, SSNA1 is enriched on microtubule damage sites, occurring both naturally, as well as induced by the microtubule severing enzyme spastin. Finally, SSNA1 binding protects microtubules against spastin's severing activity. Taken together, our results demonstrate that SSNA1 is both a potent microtubule stabilizing protein and a novel sensor of microtubule damage; activities that likely underlie SSNA1's functions on microtubule structures in cells.

SPATIAL PROBLEMS OF DYNAMIC STABILITY OF FRAME STRUCTURES

Periodic longitudinal forces in structural elements caused by operational or seismic influences, at certain values of the parameters of these forces can cause the occurrence and growing of transverse oscillations of these elements. This phenomenon is called parametric resonance or loss of dynamic stability. In the works of N. M. Belyaev, N. M. Krylov, М. М. Bogolyubov, E. Mettler, V. N. Chelomey, V. V. Bolotin flat problems of dynamic stability of frame structures were investigated. In this paper the modified Bolotin’s method, proposed to solve flat problems of dynamic stability of frames, is used. Instead of the deformation method used by V. V. Bolotin to construct analytical expressions of deflections of frame rods, in the modified method the numerical-analytical method of boundary elements is used. The article proposes a method for constructing domains of dynamic instability of frames in the space of parameters (frequency and amplitude) of seismic and operational dynamic influences that cause longitudinal forces in the rods, which periodically change over time and lead to unlimited growth of transverse oscillations amplitudes in the domains of instability. The proposed method is demonstrated in example, which considers the spatial problem of dynamic stability of a П-shaped frame with two concentrated masses located on it, which are under the action of vertical periodic forces. These forces create periodic longitudinal forces in the vertical rods of the frame. Areas of dynamic instability of the frame were constructed. Taking into account the destructive effect of oscillations is important for practical application. The most dangerous destructive effect of oscillations is observed in earthquakes and explosions. The study of this action makes it possible to avoid undesirable consequences of oscillations by limiting their level and to solve important practical problems of the dynamics of structures. Solving dynamics problems is a difficult problem. Dynamic calculation of structures provides their bearing capacity under the combined action of static and dynamic loads.

STUDY OF SPATIAL PROBLEMS OF DYNAMIC STABILITY OF REINFORCED CONCRETE FRAMES

The article proposes a method for constructing areas of dynamic instability of reinforced concrete frames in the space of parameters (frequency and amplitude) of seismic and operational dynamic impacts that cause the appearance of longitudinal forces in the bars of structures, which periodically change in time and lead to an unlimited increase in amplitudes of transverse vibrations when the values of these parameters are in the areas of instability. The proposed method is demonstrated by a specific example, which considers the spatial problem of dynamic stability of a П-shaped frame with two concentrated masses located on it, which are under the action of vertical periodic forces. These forces create periodic longitudinal forces in the vertical rods of the frame. Areas of dynamic instability of the frame are constructed. From the point of view of human activity, fluctuations can be both beneficial and harmful. We can observe vibrations of various buildings, structures, bridges, which cause additional stresses and deformations of these structures, have a harmful effect on their safe functioning. Too intense fluctuations lead to serious consequences. This leads to the destruction of individual elements of the structure and, as a result, to accidents. The most destructive effect of vibrations is observed during earthquakes and explosions. The study of vibrations is of great practical importance. This avoids the unwanted effects of fluctuations by limiting their level. Only on the basis of a deep study of various types of vibrations can important practical problems of the dynamics of structures be solved. Solving dynamics problems is a complex problem. In contrast to static calculation, when studying oscillations, one has to take into account an additional factor – time. The dynamic design of structures provides them with bearing capacity under the combined action of static and dynamic loads. A construction will be considered as a system with an infinite number of elementary masses distributed over it with an infinitely large number of dynamic degrees of freedom.

Delirium, Caffeine, and Perioperative Cortical Dynamics

Delirium is a major public health issue associated with considerable morbidity and mortality, particularly after surgery. While the neurobiology of delirium remains incompletely understood, emerging evidence suggests that cognition requires close proximity to a system state called criticality, which reflects a point of dynamic instability that allows for flexible access to a wide range of brain states. Deviations from criticality are associated with neurocognitive disorders, though the relationship between criticality and delirium has not been formally tested. This study tested the primary hypothesis that delirium in the postanesthesia care unit would be associated with deviations from criticality, based on surrogate electroencephalographic measures. As a secondary objective, the impact of caffeine was also tested on delirium incidence and criticality. To address these aims, we conducted a secondary analysis of a randomized clinical trial that tested the effects of intraoperative caffeine on postoperative recovery in adults undergoing major surgery. In this substudy, whole-scalp (16-channel) electroencephalographic data were analyzed from a subset of trial participants (n = 55) to determine whether surrogate measures of neural criticality – (1) autocorrelation function of global alpha oscillations and (2) topography of phase relationships via phase lag entropy – were associated with delirium. These measures were analyzed in participants experiencing delirium in the postanesthesia care unit (compared to those without delirium) and in participants randomized to caffeine compared to placebo. Results demonstrated that autocorrelation function in the alpha band was significantly reduced in delirious participants, which is important given that alpha rhythms are postulated to play a vital role in consciousness. Moreover, participants randomized to caffeine demonstrated increased alpha autocorrelation function concurrent with reduced delirium incidence. Lastly, the anterior-posterior topography of phase relationships appeared most preserved in non-delirious participants and in those receiving caffeine. These data suggest that early postoperative delirium may reflect deviations from neural criticality, and caffeine may reduce delirium risk by shifting cortical dynamics toward criticality.

Dynamic Instability of Functionally Graded Carbon Nanotubes-Reinforced Composite Joined Conical-Cylindrical Shell

In this paper, dynamic instability of functionally graded carbon nanotubes (CNTs)-reinforced composite joined conical-cylindrical shell in supersonic flow is analyzed numerically. The higher-order shear deformation theory is applied to describe the stress–strain state of thin-walled structure. The assumed-mode method is used to derive the finite degrees-of-freedom dynamical system, which describes the structure motions. The structure motions are expanded by using the eigenmodes, which are obtained by the Rayleigh–Ritz method. The trial functions, which satisfy the continuity conditions at the cylindrical-cone junction, are used to obtain the eigenmodes. The properties of free vibrations of thin-walled structure are analyzed numerically. The dynamic instability of the joined conical-cylindrical shell in supersonic flow is analyzed using the characteristic exponents. As follows from the numerical study, the dynamic instability is arisen due to the Hopf bifurcation. The dependences of the supersonic flow critical pressure on the Mach number and the type of CNTs distribution are analyzed numerically.