scholarly journals In Situ Cell Signalling of the Hippo-YAP/TAZ Pathway in Reaction to Complex Dynamic Loading in an Intervertebral Disc Organ Culture

2021 ◽  
Vol 22 (24) ◽  
pp. 13641
Author(s):  
Andreas S. Croft ◽  
Ysaline Roth ◽  
Katharina A. C. Oswald ◽  
Slavko Ćorluka ◽  
Paola Bermudez-Lekerika ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Dynamic Loading ◽  
Hippo Pathway ◽  
Cell Signalling ◽  
High Stress ◽  
Significant Loss ◽  
Clear Correlation ◽  
Complex Dynamic ◽  
Stress Regime ◽  
Pathway Gene

Recently, a dysregulation of the Hippo-YAP/TAZ pathway has been correlated with intervertebral disc (IVD) degeneration (IDD), as it plays a key role in cell survival, tissue regeneration, and mechanical stress. We aimed to investigate the influence of different mechanical loading regimes, i.e., under compression and torsion, on the induction and progression of IDD and its association with the Hippo-YAP/TAZ pathway. Therefore, bovine IVDs were assigned to one of four different static or complex dynamic loading regimes: (i) static, (ii) “low-stress”, (iii) “intermediate-stress”, and (iv) “high-stress” regime using a bioreactor. After one week of loading, a significant loss of relative IVD height was observed in the intermediate- and high-stress regimes. Furthermore, the high-stress regime showed a significantly lower cell viability and a significant decrease in glycosaminoglycan content in the tissue. Finally, the mechanosensitive gene CILP was significantly downregulated overall, and the Hippo-pathway gene MST1 was significantly upregulated in the high-stress regime. This study demonstrates that excessive torsion combined with compression leads to key features of IDD. However, the results indicated no clear correlation between the degree of IDD and a subsequent inactivation of the Hippo-YAP/TAZ pathway as a means of regenerating the IVD.

scholarly journals Region Specific Response of Intervertebral Disc Cells to Complex Dynamic Loading: An Organ Culture Study Using a Dynamic Torsion-Compression Bioreactor

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72489 ◽  
Author(s):  
Samantha C. W. Chan ◽  
Jochen Walser ◽  
Patrick Käppeli ◽  
Mohammad Javad Shamsollahi ◽  
Stephen J. Ferguson ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Organ Culture ◽  
Dynamic Loading ◽  
Specific Response ◽  
Complex Dynamic ◽  
Culture Study ◽  
Disc Cells ◽  
Dynamic Torsion

scholarly journals Effect of Temperature on Stiffness of Sandstones from the Deep North Sea Basin

2020 ◽  
Author(s):  
Tobias Orlander ◽  
Katrine Alling Andreassen ◽  
Ida Lykke Fabricius
Keyword(s):  
North Sea ◽  
Temperature Effects ◽  
Mass Density ◽  
Thermal Strain ◽  
High Stress ◽  
Testing Temperature ◽  
Effect Of Temperature ◽  
Stress Regime ◽  
The North

Abstract Development of high-pressure, high-temperature (HPHT) petroleum reservoirs situated at depths exceeding 5 km and in situ temperature of 170 °C increases the demand for theories and supporting experimental data capable of describing temperature effects on rock stiffness. With the intention of experimentally investigating temperature effects on stiffness properties, we investigated three sandstones from the deep North Sea Basin. As the North Sea Basin is presently undergoing substantial subsidence, we assumed that studied reservoir sandstones have never experienced higher temperature than in situ. We measured ultrasonic velocities in a low- and high-stress regime, and used mass density and stress–strain curves to derive, respectively, dynamic and static elastic moduli. We found that in both regimes, the dry sandstones stiffens with increasing testing temperature and assign expansion of minerals as a controlling mechanism. In the low-stress regime with only partial microcrack closure, we propose closure of microcracks as the stiffening mechanism. In the high-stress regime, we propose that thermal expansion of constituting minerals increases stress in grain contacts when the applied stress is high enough for conversion of thermal strain to thermal stress, thus leading to higher stiffness at in situ temperature. We then applied an extension of Biot’s effective stress equation including a non-isothermal term from thermoelastic theory and explain test results by adding boundary conditions to the equations.

scholarly journals Effects of Asymmetric Dynamic Loading on Intervertebral Disc – towards a Scoliosis Mimicking Organ Culture Model

2016 ◽  
Vol 6 (1_suppl) ◽  
pp. s-0036-1582636-s-0036-1582636
Author(s):  
Zhen Li ◽  
Ying Zhang ◽  
Lukas Straumann ◽  
Patrick Lezuo ◽  
Marianna Peroglio ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Organ Culture ◽  
Dynamic Loading ◽  
Culture Model

scholarly journals An integrative oncogene-dependency map identifies unique vulnerabilities of oncogenic EGFR, KRAS, and RIT1 in lung cancer

2020 ◽  
Author(s):  
Athea Vichas ◽  
Naomi T. Nkinsi ◽  
Amanda Riley ◽  
Phoebe C.R. Parrish ◽  
Fujiko Duke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Spindle Assembly Checkpoint ◽  
Hippo Pathway ◽  
Spindle Assembly ◽  
Human Lung Cancer ◽  
Precision Oncology ◽  
Cancer Driver ◽  
Molecular Alterations ◽  
Pathway Gene ◽  
Genome Wide

ABSTRACTAdvances in precision oncology have transformed cancer therapy from broadly-applied cytotoxic therapy to personalized treatments based on each tumor’s unique molecular alterations. Here we investigate the oncogene-specific dependencies conferred by lung cancer driver variants of KRAS, EGFR, and RIT1. Integrative analysis of genome-wide CRISPR screens in isogenic cell lines identified shared and unique vulnerabilities of each oncogene. The non-identical landscape of dependencies underscores the importance of genotype-guided therapies to maximize tumor responses. Combining genetic screening data with small molecule sensitivity profiling, we identify a unique vulnerability of RIT1-mutant cells to loss of spindle assembly checkpoint regulators. This sensitivity may be related to a novel role of RIT1 in mitosis; we find that oncogenic RIT1M90I alters mitotic timing via weakening of the spindle assembly checkpoint. In addition, we uncovered a specific cooperation of mutant RIT1 with loss of Hippo pathway genes. In human lung cancer, RIT1 mutations and amplifications frequently co-occur with loss of Hippo pathway gene expression. These results provide the first genome-wide atlas of oncogenic RIT1-cooperating factors and genetic dependencies and identify components of the RAS pathway, spindle assembly checkpoint, and Hippo/YAP1 network as candidate therapeutic targets in RIT1-mutant lung cancer.

TEAD2, a Hippo pathway gene, is somatically mutated in gastric and colorectal cancers with high microsatellite instability

Apmis ◽  
2014 ◽  
Vol 123 (4) ◽  
pp. 359-360 ◽  
Author(s):  
Eun Mi Je ◽  
Youn Jin Choi ◽  
Yeun Jun Chung ◽  
Nam Jin Yoo ◽  
Sug Hyung Lee
Keyword(s):  
Microsatellite Instability ◽  
Hippo Pathway ◽  
Colorectal Cancers ◽  
Pathway Gene

Microstructural Characterization of Creep Tested Cryomilled NiAl-13vol. % AlN

1994 ◽  
Vol 350 ◽  
Author(s):  
A. Garg ◽  
J. D. Whittenberger ◽  
B. J. M. Aikin
Keyword(s):  
Steady State ◽  
Compressive Strain ◽  
High Stress ◽  
Microstructural Characterization ◽  
Dislocation Network ◽  
Stress Regime ◽  
Stress Diagram ◽  
Superior Mechanical Properties ◽  
Power Law Creep

AbstractCryomilling of prealloyed NiAl powders, followed by extrusion, has been used to produce a particulate strengthened NiAl-13vol.% AlN material. At 1300 K, the compressive strain rate-flow stress diagram has two distinct deformation regimes, with the transition occurring near 150 MPa. The low and the high stress regimes have power law creep exponents of ∼ 6.1 and 14.2, respectively. Microstructural characterization of the as-extruded and tested samples has been performed to develop an understanding of the superior mechanical properties of the material. The microstructure of the as-extruded material was inhomogeneous and consisted of mantle regions containing a mixture of small NiAl grains (diameter ∼ 50–150 nm) and fine AlN particles (size ∼ 5–50 nm) that surround larger NiAl grains (diameter ∼ 0.3–8.0 μm) which were mostly particle free. In the low-stress regime, samples tested to steady state exhibited a structure composed of subgrain boundaries in the particle-free NiAl grains. In addition, some of the subgrains had developed a well defined dislocation network. AlN patricles occasionally found within large NiAl grains acted as pinning centers for dislocations. Small NiAl grains and the AlN particles constituting the mantle coarsened during these tests. In the high-stress regime, samples tested to steady state exhibited a high density of dislocations in most of the particle-free NiAl grains. Subgrain boundaries were found occasionally but dislocation networks were rare. The AlN particles had not significantly coarsened due to the shorter times at temperature.

Constitutive Model for Anisotropic Creep Behaviors of Single-Crystal Ni-Base Superalloys in the Low-Temperature, High-Stress Regime

2012 ◽  
Vol 43 (6) ◽  
pp. 1861-1869 ◽  
Author(s):  
Yoon Suk Choi ◽  
Triplicane A. Parthasarathy ◽  
Christopher Woodward ◽  
Dennis M. Dimiduk ◽  
Michael D. Uchic
Keyword(s):  
Low Temperature ◽  
Constitutive Model ◽  
Single Crystal ◽  
High Stress ◽  
Stress Regime ◽  
Anisotropic Creep

scholarly journals Case Study and Failure Analysis of a total hip Stem Fracture

2015 ◽  
Vol 15 (2) ◽  
pp. 5-13 ◽  
Author(s):  
Ż. A. Mierzejewska
Keyword(s):  
Grain Size ◽  
Stress Concentration ◽  
Joint Infection ◽  
High Stress ◽  
Hardness Test ◽  
Normative Values ◽  
Clear Correlation ◽  
Element Analysis ◽  
Total Hip ◽  
Average Grain Size

AbstractA total hip replacement is a procedure that requires removal of the affected joint lesions and replacing it with artificial elements. Nevertheless, like any invasive surgery, it is associated with the risk of complications, including joint infection, fracture of the bone during and after surgery, scarring and limitation of motion of the hip, and loosening of the prosthesis. In this work we present and describe the results of its investigations. In order to determine the mechanism of failure, a broken stem components were analyzed by means of macroscopic and microscopic observations and hardness measurements. The hardness, microstructure and chemical composition of the broken part of the hip stem were analyzed. Microscopic examination revealed numerous defects in material. Among them are pores and emptiness, located on the outskirts of the tested samples and a plurality of micro-cracking, debonding and delamination of the material due to the overloading of a fatigue character. There were no changes caused by intergranular corrosion or pitting, which may indicate for an even distribution of the major alloying components such as chromium and nickel. Observations of the material by using scanning electron microscopy (SEM), clearly proved that the destruction was caused by material fatigue. The investigation showed that the crack had originated due to a high stress concentration on the lateral corner section of the stem. Large surface of the fatigue crack zone area indicated for small stresses and small crack propagation velocities. There was a clear correlation between the grain size of the steel hardness. The results of hardness test revealed a significant increase hardness of stem in relation to the normative values. In addition, the measured average grain size is less than the standard accepted. Using Solid Works simulation and FEM a model of the stem was created and analyzed in terms of strength and rated the distribution of the generated stress. The finite-element analysis confirmed that there is the highest stress concentration in the middle of the stem

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