On characterizing skeletal muscle contraction properties. Experimental and simulation methodology

The main objective of this work is to characterize the fatigue contractile properties of threedifferent rat muscles (Tibialis Anterior, Extensor Digitorium Longus and Soleus) in order toobtain experimental parameters for numerical simulations.Experiments were conducted “in vivo" on three groups (n = 6) of male Wistar rats (210 +/- 11g)using a protocol developed by authors in previous works. Muscles were subjected to anelectrical stimulus to achieve tetanic contraction during ten seconds. Digital Image Correlationwas used during tests for 3D strain and displacements measurement that allow the correlationwith the finite element simulations.By means of Computed Tomography, a precise reconstruction of both bone and muscle of therat hindlimb geometry was obtained. The methodology proposed allows to obtain and validatecomputational simulations of skeletal muscle fatigue under different characteristics related tofiber types.6

Selective anticancer and antimicrobial metallodrugs based on Gold(III) dithiocarbamate complexes

New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of moderate strength to the BSA protein. Furthermore, none of the complexes exhibited reduction or decomposition reactions, presenting excellent physiological stability. The in vitro cytotoxic effect was evaluated on human colon cancer cell line Caco-2/TC7, and the complexes showed great antiproliferative activity and excellent selectivity, as much less effect was detected on normal Caco-2/TC7 cells. Most of the complexes exhibit antiproliferative activity that was better than or similar to auranofin, and at least nine times better than that of cisplatin. Its action mechanism is still under discussion since no evidence of cell cycle arrest was found, but an antioxidant role was shown for some of the selective complexes. All complexes were also tested as antimicrobial drugs, exhibiting good activity towards S. aureus and E. coli. bacteria and C. albicans and C. neoformans fungi. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

Chemo-mechanical model for skeletal muscle contraction

Generation of force in skeletal muscle tissue depends on both chemical and mechanical phenomena. In this work, considering the kinetics of cross bridges, a one dimensional model has been proposed for predicting the isometric force according to the intracellular calcium ion distribution

Assessing the role of Ca2+ in skeletal muscle fatigue using a multi-scale continuum model

The Calcium ion Ca2+ plays a critical role as an initiator and preserving agent of the cross-bridge cycle in the force generation of skeletal muscle. A new multi-scale chemo-mechanical model is presented in order to analyze the role of Ca2+ in muscle fatigue and to predict fatigue behavior. To this end, a cross-bridge kinematic model was incorporated in a continuum based mechanical model, considering a thermodynamic compatible framework. The contractile velocity and the generated active force were directly related to the force-bearing states that were considered for the cross-bridge cycle. In order to determine the values of the model parameters, the output results of an isometric simulation were initially fitted with experimental data obtained for rabbit Extensor Digitorum Longus muscle. Furthermore, a simulated force-velocity curve under concentric contractions was compared with reported experimental results. Finally, by varying the Ca2+ concentration level and its kinetics in the tissue, the model was able to predict the evolution of the active force of an experimental fatigue protocol. The good agreement observed between the simulated results and the experimental outcomes proves the ability of the model to reproduce the fatigue behavior and its applicability for more detailed multidisciplinary investigations related to chemical conditions in muscle performance

Effect of cryopreserved amniotic membrane on the mechanical properties of skeletal muscle after strabismus surgery in rabbits

Purpose: To study the functional recovery of the superior rectus muscle (SRM) after its partial resection in a rabbit model with and without cryopreserved amniotic membrane (AM). Material and methods: Resection of the right and left SRMs of 30 rabbits was performed. On the left eyes, a single sheet of equine cryopreserved AM was placed covering the muscle edge sutured. Active and passive mechanical properties of muscles operated with and without AM were monitored over time at 30 (n = 10), 60 (n = 10), and 90 (n = 10) days after surgery. Muscle samples were extracted and electrically stimulated to register the force exerted by the samples, characterizing its active behavior. They were, then, subjected to stretching test to obtain its resistance to deformation, known as passive behavior. Moreover, right and left eyes of a control group (n = 5) were equally subjected to active and passive tests to characterize the physiological behavior of SRM muscles. Results: On active function examination, statistically significant differences were documented between the following: control vs AM and no AM at 30 days (p = 0.002 and p = 0.04, respectively). All other comparisons were insignificant (p > 0.05). On passive function analysis, significant differences were only found between control vs. no AM at 30 days (p = 0.004) and between AM vs. no AM at 30 days (p = 0.002). Indeed, muscle operated without AM did not recover a normal passive function until 60 days after surgery. Conclusion: Cryopreserved AM is effective in accelerating recovery of SRM passive function in rabbits. Nevertheless, AM produced no significant effect on recovery of SRM active function.

Active behavior of abdominal wall muscles: Experimental results and numerical model formulation

In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047. ±. 34. g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction

Recursive internetwork architecture, investigating RINA as an alternative to TCP/IP (IRATI)

Driven by the requirements of the emerging applications and networks, the Internet has become an architectural patchwork of growing complexity which strains to cope with the changes. Moore’s law prevented us from recognising that the problem does not hide in the high demands of today’s applications but lies in the flaws of the Internet’s original design. The Internet needs to move beyond TCP/IP to prosper in the long term, TCP/IP has outlived its usefulness. The Recursive InterNetwork Architecture (RINA) is a new Internetwork architecture whose fundamental principle is that networking is only interprocess communication (IPC). RINA reconstructs the overall structure of the Internet, forming a model that comprises a single repeating layer, the DIF (Distributed IPC Facility), which is the minimal set of components required to allow distributed IPC between application processes. RINA supports inherently and without the need of extra mechanisms mobility, multi-homing and Quality of Service, provides a secure and configurable environment, motivates for a more competitive marketplace and allows for a seamless adoption. RINA is the best choice for the next generation networks due to its sound theory, simplicity and the features it enables. IRATI’s goal is to achieve further exploration of this new architecture. IRATI will advance the state of the art of RINA towards an architecture reference model and specifcations that are closer to enable implementations deployable in production scenarios. The design and implemention of a RINA prototype on top of Ethernet will permit the experimentation and evaluation of RINA in comparison to TCP/IP. IRATI will use the OFELIA testbed to carry on its experimental activities. Both projects will benefit from the collaboration. IRATI will gain access to a large-scale testbed with a controlled network while OFELIA will get a unique use-case to validate the facility: experimentation of a non-IP based Internet

Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation

This is the final version of the article. Available from Public Library of Science via the DOI in this record.TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.This work was funded by grants from the Spanish Ministry of Science and Innovation and the European Regional Development Fund (ERDF/FEDER) (BFU2010-18971), Zaragoza University (UZ2014-BIO-03), European Social Found (ESF) and the Aragon Regional Government (B61) and the Foundation for the Study of Inflammatory Bowel Diseases in Aragón (ARAINF 012/2008). ARAID Foundation supported J.P. (SAF2014-54763-C2-1-R) and E. Layunta is a PhD student fellow from Aragon Regional Government (B022/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

NOD2 Modulates Serotonin Transporter and Interacts with TLR2 and TLR4 in Intestinal Epithelial Cells

Background/Aims: Serotonin (5-HT) is a chief modulator of intestinal activity. The effects of 5-HT depend on its extracellular availability, which is mainly controlled by serotonin transporter (SERT), expressed in enterocytes. On the other hand, innate immunity, mediated by Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), is known to control intestinal microbiota and maintain intestinal homeostasis. The dysregulation of the intestinal serotonergic system and innate immunity has been observed in in ammatory bowel diseases (IBD), the incidence of which has severely increased all over the world. The aim of the present study, therefore, was to analyze the effect of NOD2 on intestinal SERT activity and expression, as well as to study the crosstalk of NOD2 with TLR2 and TLR4. Methods: Intestinal epithelial cell line Caco-2/TC7 was used to analyze SERT activity and SERT, NOD2, TLR2 and TLR4 molecular expression by real-time PCR and western blotting. Moreover, intestinal tract (ileum and colon) from mice de cient in TLR2, TLR4 or TLR2/4 receptors was used to test the interdependence of NOD2 with these TLR receptors. Results: NOD2 activation inhibits SERT activity in Caco-2/TC7 cells, mainly due to the decrement of SERT molecular expression, with RIP2/RICK being the intracellular pathway involved in this effect. This inhibitory effect on SERT would yield an increment of extracellular 5-HT availability. In this sense, 5-HT strongly inhibits NOD2 expression. In addition, NOD2 showed greater interdependence with TLR2 than with TLR4. Indeed, NOD2 expression signi cantly increased in both cells treated with TLR2 agonists and the intestinal tract of Tlr2-/- mice. Conclusions: It may be inferred from our data that NOD2 could play a role in intestinal pathophysiology not only through its inherent innate immune role but also due to its interaction with other receptors as TLR2 and the modulation of the intestinal serotonergic system decreasing SERT activity and expression