Aladin M. Boriek

Amongst brain structures, we identified a virtual void at the juxta– and paranode, within the intraperiod myelin layers, V _IMI , as potential candidate for quantum near-ideal topological insulation. The insulation was extensively weighed here according to current findings. Values of biological and physical boundaries must be exact and a single missing/inexact element defining the anatomy, physiology, biochemistry, cytology, histology, and nano, leads to inaccurate boundaries/quantum equations of the myelin system. We determined the threshold of quantum coherence to decoherence. A propagating internodal electromagnetic interaction through the V _IMI void can be represented via Hamiltonian and entanglement. We tested three potential mechanisms for ion K ⁺ data storage. 1. Quantum tunneling through a dielectric, i.e . single myelin layer. 2. Quantum tunneling through squeezing void, V _IMI . The action potential is accompanied by mechanical axonal waves and myelin layers compression. Compression reduces the WKB action, and exponentially increases in transmission-tunneling probability. Resonance tunneling may add orders-of-magnitude boosts. 3. Classical squeezing passage. Quantum coherence, tunneling (1) and (2) are theoretically valid and testable, (1) at highly restricted parameter threshold. Unlike quantum tunneling, classical physic passage does not allow fine voltage-controlled metering, sorting, organizing the data storage, later rendering the retrieving impossible.

Despite extensive study of cellular mechanisms underlying long-term potentiation, no single specific protein or gene has been identified which encodes an individual unit of information, or memory bit. Indeed, the brain engram remains a knowledge gap. The theory of exclusion led us to cancel one-by-one several unrealistic biological options, suggesting that the explanation resides somewhere else. Superposition of up to concentric 300 myelin layers, spiraled, and highly compacted wrapping a single axon and each wrap could host hundreds to thousands of niches, as memory cells, collectively consisting of a massive array of cells. The disjointed 3D spatial superposition allows storage of charges, nodes not facing from a layer to next. The thickness of a single myelin layer ranges from 7.0 to 20 nm. The dimension scale is approximately the exact dimensions of the charge trap, the tunnel and dielectric also equipping current AI microchips. Stored charges are positive ions, with similar effect whether charges are negative or positive charges creating an electromagnetic field. To write data, following an action potential, this voltage applies to the control gates of the myelin layers producing an ionic charge injection. This causes charges to gain energy and tunnel through the myelin layer across Ranvier nodes, via quantum tunneling, and deep into the concentric myelin multilayers. This is creating an insulated trapping of K+ ions isolated from the system. In a long white matter tract bundle, the near-perfect isolation of millions of axons within compressed myelin wrap-ion channel K+/Na+ systems provides quantum coherence and precision of asynchronous firing property. The injected ionic charges (K+) become physically stuck in traps within the myelin layers. The K+ ions may not move freely, completely trapped after AP ceases. Mirroring a single-bit, single-level-cell, a trapped ionic charge (ions K+) may represent a 1, while an empty cell (absence of K+) represents a 0. The trial-and-error process, with a Bayesian inference which may have also been the core evolution of the learning human brain. Based on selected mathematical equations, we analyzed the general scheme on how deep learning may be embedded in the brain

Background: Change in 6-min walk distance (6MWD) over time serves as a measure of change in functional exercise performance. We analysed a large cohort of current or former tobacco smokers over a 5-year period to identify correlates of 6MWD decline. Methods: A total of 4734 participants with normal spirometry or spirometric evidence of chronic obstructive pulmonary disease (COPD) who completed a 5-year follow-up in the COPDGene study were included. Baseline and 5-year assessments included 6MWD, spirometry, St. George’s Respiratory Questionnaire (SGRQ), gender, race and CT measures of emphysema, gas trapping and airway wall thickness. 6MWD decline correlates relative to baseline and 5-year changes were examined using univariate and multivariate linear regression. Results: At baseline, 2573 had normal spirometry; 487 were classified as GOLD1, 1044 as GOLD2, 514 as GOLD3 and 116 as GOLD4. Average 5-year decline in 6MWD was 35.6±101.7 (SD) metres (p2 =12.1% and 9.1%, respectively). 5 year change in variables assessed (including FEV ₁ and SGRQ) explained only small fractions of 6MWD decline variance (each R ² ≤5%). Conclusion: 6MWD declined significantly, but with high variability; spirometry, CT, health status, demographic and anthropometric measures accounted for only small portions of this variance. Our findings suggest that a meaningful decline in 6MWD observed over 5 years in COPD patients is in large part related to factors other than decline in pulmonary structure or function.

Data from the current study support the hypothesis that the pressure-generating capacity of the diaphragm at high lung volume is compromised primarily due to a mechanism that involves a combined mechanical effect of hyperinflation and substantial muscle contraction rather than a significant loss of its muscle fiber curvature.

Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm—a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory uncovered that stretching the diaphragm in either the longitudinal or transverse direction activates distinct mechanotransduction pathways. This indicates that signaling pathways in the diaphragm muscle are regulated in an anisotropic manner. In this review paper, we discussed the underlying mechanisms that regulate the anisotropic signaling pathways in the diaphragmatic muscle, emphasizing the mechanical role of cytoskeletal proteins in this context. Furthermore, we explored the regulatory mechanisms governing mechanosensitive gene transcription, including microRNAs (mechanomiRs), within the diaphragm muscle. Finally, we examined potential links between anisotropic signaling in the diaphragm muscle and various skeletal muscle disorders.

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms of relevance for implant integration such as the proliferation and differentiation of cell precursors and the immune response to the implant. The influence of substrate stiffness on the regulation of the immune response is not completely understood and the progress in this field can contribute to the designing of an adequate implant design. Though the use of nano-biomaterials has been proved to contribute to implant success, the relationship between grain size and stiffness of the material has not been explored in the biomedical field; filling these gaps in the knowledge of biomaterials will highly contribute to the design of biomaterials that could take advantage of the cells sensing and response to the stiffness at the implant interface.

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast differentiation, and the introduction of the mechanomiR-200c antagomir restored the stretch effect. This suggests that stretch blocks differentiation, in part, through mechanomiR-200c. The gene encoding the transcription factor FoxO3 is a known direct target of mechanomiR-200c. Interestingly, MyoD binds to the mechanomiR-200c promoter in differentiating myoblasts, whereas stretch appears to reverse such binding. Our data further demonstrate that the levels of mechanomiR-200c are robustly elevated during the early stage of the muscle repair process in young mice, but not in the injured muscle of aged mice. Overall, we identified a novel pathway, MyoD/mechanomiR-200c/FoxO3a, and the potential mechanism by which stretch inhibits myoblast differentiation.

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production costs must be addressed. Research is ongoing to improve the design and functionality of liposomes. They can potentially monitor bone implants as non-invasive imaging agents, enabling early detection of complications and timely interventions. This approach can enhance patient outcomes and extend the longevity of implants, making it a promising strategy for better patient care and implant success.

The muscular dystrophy with myositis (mdm) mouse model results in a severe muscular dystrophy due to an 83-amino-acid deletion in the N2A region of titin, an expanded sarcomeric protein that functions as a molecular spring which senses and modulates the response to mechanical forces in cardiac and skeletal muscles. ANKRD1 is one of the muscle ankyrin repeat domain proteins (MARPs) a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. The aberrant over-activation of Nuclear factor Kappa B (NF-κB) and the Ankyrin-repeat domain containing protein 1 (ANKRD1) occurs in several models of progressive muscle disease including Duchenne muscular dystrophy. We hypothesized that mechanical regulation of ANKRD1 is mediated by NF-κB activation in skeletal muscles and that this mechanism is perturbed by small deletion of the stretch-sensing titin N2A region in the mdm mouse. We applied static mechanical stretch of the mdm mouse diaphragm and cyclic mechanical stretch of C₂C₁₂ myotubes to examine the interaction between NF−κΒ and ANKRD1 expression utilizing Western blot and qRTPCR. As seen in skeletal muscles of other severe muscular dystrophies, an aberrant increased basal expression of NF-κB and ANKRD1 were observed in the diaphragm muscles of the mdm mice. Our data show that in the mdm diaphragm, basal levels of NF-κB are increased, and pharmacological inhibition of NF-κB does not alter basal levels of ANKRD1. Alternatively, NF-κB inhibition did alter stretch-induced ANKRD1 upregulation. These data show that NF-κB activity is at least partially responsible for the stretch-induced expression of ANKRD1.

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, particularly accounting for the percentage and nature of crystal boundaries. Recognising and understanding these physical and chemical characteristics establish the groundwork for formulating precise guidelines crucial in the development of the forthcoming generation of biomedical devices. The significance of nanoscale surface in favourably modulating the cellular functionality is described with the aim to provide the solution to the current day challenges in the biomedical arena. Furthermore, the perspective presented advances the nano-bio science forward by implying that the nanoscale structure induces chemical and physical changes that can be considered responsible for favourable modulation of cellular activity in the living organism.