Ovarian Biomechanics: From Health to Disease

Biomechanics is a physical phenomenon which mainly related with deformation and movement of life forms. As a mechanical signal, it participates in the growth and development of many tissues and organs, including ovary. Mechanical signals not only participate in multiple processes in the ovary but also play a critical role in ovarian growth and normal physiological functions. Additionally, the involvement of mechanical signals has been found in ovarian cancer and other ovarian diseases, prompting us to focus on the roles of mechanical signals in the process of ovarian health to disease. This review mainly discusses the effects and signal transduction of biomechanics (including elastic force, shear force, compressive stress and tensile stress) in ovarian development as a regulatory signal, as well as in the pathological process of normal ovarian diseases and cancer. This review also aims to provide new research ideas for the further research and treatment of ovarian-related diseases.

AGUSTIN DE BETANCOURT AS CREATOR OF OPTICAL TELEGRAPH MACHINE USED ON THE FIRST EUROPEAN RAILWAY LINES AND PRECURSOR OF RAILWAY SIGNALLING SYSTEMS

The origin of signalling principles, their purpose and development since the 4th century BC are described. Claude Chappe' s research on the peculiarities of human vision and the rationale for the choice of colors for the optical telegraph are presented. These principles are used in modern rail and road signaling systems with slight modifi cations to refl ect the development of technology. The transmission apparatus and the Claude Chappe alphabet are presented, documentary examples of its use in France are proposed, and the main disadvantages of this principle of data transmission are indicated. Further in the article, an alternative principle of data transmission using a single semaphore wing in an optical telegraph is presented. It was developed and introduced in 1798 between Madrid and Cadiz (Spain) by Agustin de Betancourt. The article shows the diagrams of the optical telegraph apparatus of Agustin de Betancourt, and also gives its comparison with fi rst mechanical signals used in railway transport. With references to historical documents and evidence, the evolution of the optical telegraph by Agustin de Betancourt from data transmission systems between cities to systems for the exchange of information between neighboring railway posts and stations on the fi rst railway lines is presented. The evolution of the telegraph from mechanical devices announcing the train approach to the railway post to the signals for train drivers thanks to the change of wing position is shown. As a transitional stage from mechanical to electrical signals in railway transport, the principle of operation of semaphores with kerosene lamps lit at night with light fi lters mechanically connected to the position of the wing is explained. Based on development of mechanical signals, the historical reasons for signal aspect with two lamps in diff erent modern signalling systems are presented. The article opens a new, previously little-known page of the activities by Agustin de Betancourt, who was not only the fi rst rector of the fi rst transport high school in Russia but also one of developers of data transmission systems used optical telegraph. His inventions such as mechanical signal with one wing are using in improved form in railway signalling systems up today.

Performance evaluation of accelerometers ADXL345 and MPU6050 exposed to random vibrational input

The use of vibration monitors is a well-established practice in industrial maintenance, usually vibration sensors are positioned at specific points on the monitored machinery and data are continuously collected to feed a machine operating health control system. Nevertheless, the technology for obtaining the signal, its treatment and analysis is generally expensive, and the financial return is not evident, which justifies the development of low-cost alternatives technologies. In this work was performed an analysis of the responses of two Micro-Electro-Mechanical accelerometers, models ADXL345 and MPU6050, exposed to a low intensity random signal and standard operating frequency. The objective of the analysis was to verify the capacity of these devices to be used as mechanical vibration sensors for rotating machines. For this purpose, offset shift analyzes of the sensors due to the Earth's gravitational field were performed, as well as vibrational spectrum and rectification errors analysis under multiple conditions. The data pointed to a greater uniformity of the MPU6050 response, while several behavioral anomalies were seen in the ADXL345, when these sensors are exposed to the same mechanical signal. The qualitative and quantitative behavior of MPU6050 rectification error was consistent with reported in the literature. It was noted that the methodology used can profile the behavior of sensors, however, it is not sufficient to safely justify the inaccuracies, requiring that the tests be performed on a statistically representative number of sensors from different manufacturers and batches.

Mechanically transduced immunosorbent assay to measure protein-protein interactions

Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry. Yet, conventional methods rely upon the law of mass action and cannot measure many PPIs due to a scarcity of reagents and limitations in the measurable affinity ranges. Here, we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that correlates to binding potential. The mechanically transduced immunosorbent (METRIS) assay utilizes rolling magnetic probes to measure PPI interaction affinities. METRIS measures the translational displacement of protein-coated particles on a protein-functionalized substrate. The translational displacement scales with the effective friction induced by a PPI, thus producing a mechanical signal when a binding event occurs. The METRIS assay uses as little as 20 pmols of reagents to measure a wide range of affinities while exhibiting a high resolution and sensitivity. We use METRIS to measure several PPIs that were previously inaccessible using traditional methods, providing new insights into epigenetic recognition.

Mechanosensitive control of mitotic entry

As cells prepare to divide, they must ensure that enough space is available to assemble the mitotic machinery without perturbing tissue homeostasis. To do so, cells undergo a series of biochemical reactions regulated by cyclin B1-CDK1 that trigger the reorganization of the actomyosin cytoskeleton and ensure the coordination of cytoplasmic and nuclear events. Along with the biochemical events that control mitotic entry, mechanical forces have recently emerged as important players in the regulation of cell cycle events. However, the exact link between mechanical forces and the biochemical events that control mitotic progression remains to be established. Here, we identify a mechanical signal on the nucleus that sets the time for nuclear envelope permeabilization and mitotic entry. This signal relies on nuclear unfolding during the G2-M transition, which activates the stretch-sensitive cPLA2 on the nuclear envelope. This activation upregulates actomyosin contractility, determining the spatiotemporal translocation of cyclin B1 in the nucleus. Our data demonstrate how the mechanosensitive behaviour of cyclin B1 ensures timely and efficient mitotic spindle assembly and prevents chromosomal instability.

Strain induced mechanoresponse depends on cell contractility and BAG3-mediated autophagy

Basically all mammalian tissues are constantly exposed to a variety of environmental mechanical signals. Depending on the signal strength, mechanics intervenes in a multitude of cellular processes and is thus capable to induce simple cellular adaptations but also complex differentiation processes and even apoptosis. The underlying recognition typically depends on mechanosensitive proteins, which most often sense the mechanical signal for the induction of a cellular signaling cascade by changing their protein conformation. However, the fate of mechanosensors after mechanical stress application is still poorly understood and it remains unclear whether protein degradation pathways affect the mechanosensitivity of cells. Here, we show that cyclic stretch induces autophagosome formation in a time-dependent manner. Formation depends on the cochaperone BAG3 and thus likely involves BAG3-mediated chaperone-assisted selective autophagy. Furthermore, we demonstrate that strain-induced cell reorientation is clearly delayed upon inhibition of autophagy, suggesting a bidirectional crosstalk between mechanotransduction and autophagic degradation. The strength of the observed delay depends on stable adhesion structures and stress fiber formation in a RhoA-dependent manner.

Mechanotaxis directs Pseudomonas aeruginosa twitching motility

The opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellular filaments called type IV pili (T4P). Single cells twitch by sequential T4P extension, attachment, and retraction. How single cells coordinate T4P to efficiently navigate surfaces remains unclear. We demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from T4P in a process called mechanotaxis. The Chp chemotaxis-like system controls the balance of forward and reverse twitching migration of single cells in response to the mechanical signal. Collisions between twitching cells stimulate reversals, but Chp mutants either always or never reverse. As a result, while wild-type cells colonize surfaces uniformly, collision-blind Chp mutants jam, demonstrating a function for mechanosensing in regulating group behavior. On surfaces, Chp senses T4P attachment at one pole, thereby sensing a spatially resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stimulates polarization favoring forward migration, while PilH inhibits polarization, inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localization of response regulators establishes a signaling landscape known as local excitation–global inhibition in higher-order organisms, identifying a conserved strategy to transduce spatially resolved signals.