scholarly journals Transit and integration of extracellular mitochondria in human heart cells

2017 ◽  
Author(s):  
Douglas B. Cowan ◽  
Rouan Yao ◽  
Jerusha K. Thedsanamoorthy ◽  
David Zurakowski ◽  
Pedro J. del Nido ◽  
...  

Tissue ischemia adversely affects the function of mitochondria, which results in impairment of oxidative phosphorylation and compromised recovery of the affected organ. The impact of ischemia on mitochondrial function has been most extensively studied in the heart because of the morbidity and mortality associated with injury to this organ. Because conventional methods to preserve cell viability and function following an ischemic injury are limited in their efficacy, we developed a unique approach to protect the heart by transplanting respiration-competent mitochondria isolated from a non-ischemic tissue to the ischemic region. Our experiments in animals have shown that transplantation of isolated mitochondria to injured heart tissue leads to decreases in cell death, increases in energy production, and improvements in contractile function. We also discovered that exogenously-derived mitochondria injected or perfused into ischemic hearts were readily internalized by cardiac cells through actin-dependent endocytosis. Here, we describe the use of three-dimensional super-resolution microscopy and transmission electron microscopy to determine the intracellular fate of exogenous mitochondria in non-dividing human iPS-derived cardiomyocytes and dividing primary human cardiac fibroblasts. We show isolated mitochondria are internalised in human cardiac cells within minutes and then transported to endosomes and lysosomes. The majority of exogenous mitochondria escape from these compartments and fuse with the endogenous mitochondrial network, while some organelles are degraded through hydrolysis. Understanding this process may guide the development of treatments directed at replacing or augmenting impaired mitochondria in ischemic tissues and provide new options to rejuvenate dysfunctional mitochondria in a wide range of human diseases and disorders.

2017 ◽  
Vol 824 ◽  
pp. 866-885 ◽  
Author(s):  
Ali Mazloomi Moqaddam ◽  
Shyam S. Chikatamarla ◽  
Iliya V. Karlin

Recent experiments with droplets impacting macro-textured superhydrophobic surfaces revealed new regimes of bouncing with a remarkable reduction of the contact time. Here we present a comprehensive numerical study that reveals the physics behind these new bouncing regimes and quantifies the roles played by various external and internal forces. For the first time, accurate three-dimensional simulations involving realistic macro-textured surfaces are performed. After demonstrating that simulations reproduce experiments in a quantitative manner, the study is focused on analysing the flow situations beyond current experiments. We show that the experimentally observed reduction of contact time extends to higher Weber numbers, and analyse the role played by the texture density. Moreover, we report a nonlinear behaviour of the contact time with the increase of the Weber number for imperfectly coated textures, and study the impact on tilted surfaces in a wide range of Weber numbers. Finally, we present novel energy analysis techniques that elaborate and quantify the interplay between the kinetic and surface energy, and the role played by the dissipation for various Weber numbers.


2018 ◽  
Vol 860 ◽  
pp. 739-766 ◽  
Author(s):  
Rémi Bourguet

The flow-induced vibrations of an elastically mounted circular cylinder, free to oscillate in an arbitrary direction and forced to rotate about its axis, are examined via two- and three-dimensional simulations, at a Reynolds number equal to 100, based on the body diameter and inflow velocity. The behaviour of the flow–structure system is investigated over the entire range of vibration directions, defined by the angle $\unicode[STIX]{x1D703}$ between the direction of the current and the direction of motion, a wide range of values of the reduced velocity $U^{\star }$ (inverse of the oscillator natural frequency) and three values of the rotation rate (ratio between the cylinder surface and inflow velocities), $\unicode[STIX]{x1D6FC}\in \{0,1,3\}$, in order to cover the reference non-rotating cylinder case, as well as typical slow and fast rotation cases. The oscillations of the non-rotating cylinder ($\unicode[STIX]{x1D6FC}=0$) develop under wake-body synchronization or lock-in, and their amplitude exhibits a bell-shaped evolution, typical of vortex-induced vibrations (VIV), as a function of $U^{\star }$. When $\unicode[STIX]{x1D703}$ is increased from $0^{\circ }$ to $90^{\circ }$ (or decreased from $180^{\circ }$ to $90^{\circ }$), the bell-shaped curve tends to monotonically increase in width and magnitude. For all angles, the flow past the non-rotating body is two-dimensional with formation of two counter-rotating spanwise vortices per cycle. The behaviour of the system remains globally the same for $\unicode[STIX]{x1D6FC}=1$. The principal effects of the slow rotation are a slight amplification of the VIV-like responses and widening of the vibration windows, as well as a limited asymmetry of the responses and forces about the symmetrical configuration $\unicode[STIX]{x1D703}=90^{\circ }$. The impact of the fast rotation ($\unicode[STIX]{x1D6FC}=3$) is more pronounced: VIV-like responses persist over a range of $\unicode[STIX]{x1D703}$ but, outside this range, the system is found to undergo a transition towards galloping-like oscillations characterised by amplitudes growing unboundedly with $U^{\star }$. A quasi-steady modelling of fluid forcing predicts the emergence of galloping-like responses as $\unicode[STIX]{x1D703}$ is varied, which suggests that they could be mainly driven by the mean flow. It, however, appears that flow unsteadiness and body motion remain synchronised in this vibration regime where a variety of multi-vortex wake patterns are uncovered. The interaction with flow dynamics results in deviations from the quasi-steady prediction. The successive steps in the evolution of the vibration amplitude versus $U^{\star }$, linked to wake pattern switch, are not captured by the quasi-steady approach. The flow past the rapidly-rotating, vibrating cylinder becomes three-dimensional over an interval of $\unicode[STIX]{x1D703}$ including the in-line oscillation configuration, with only a minor effect on the system behaviour.


2021 ◽  
Vol 13 (603) ◽  
pp. eabd1817
Author(s):  
Jacqueline M. Bliley ◽  
Mathilde C. S. C. Vermeer ◽  
Rebecca M. Duffy ◽  
Ivan Batalov ◽  
Duco Kramer ◽  
...  

The role that mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)–derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained contractile shortening of >10%. To do this, three-dimensional (3D) EHTs were integrated with an elastic polydimethylsiloxane strip providing mechanical preload and afterload in addition to enabling contractile force measurements based on strip bending. Our results demonstrated that dynamic loading improves the function of wild-type EHTs on the basis of the magnitude of the applied force, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output.


Energies ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 8327
Author(s):  
Roberto Pacciani ◽  
Michele Marconcini ◽  
Francesco Bertini ◽  
Simone Rosa Taddei ◽  
Ennio Spano ◽  
...  

This paper presents an assessment of machine-learned turbulence closures, trained for improving wake-mixing prediction, in the context of LPT flows. To this end, a three-dimensional cascade of industrial relevance, representative of modern LPT bladings, was analyzed, using a state-of-the-art RANS approach, over a wide range of Reynolds numbers. To ensure that the wake originates from correctly reproduced blade boundary-layers, preliminary analyses were carried out to check for the impact of transition closures, and the best-performing numerical setup was identified. Two different machine-learned closures were considered. They were applied in a prescribed region downstream of the blade trailing edge, excluding the endwall boundary layers. A sensitivity analysis to the distance from the trailing edge at which they are activated is presented in order to assess their applicability to the whole wake affected portion of the computational domain and outside the training region. It is shown how the best-performing closure can provide results in very good agreement with the experimental data in terms of wake loss profiles, with substantial improvements relative to traditional turbulence models. The discussed analysis also provides guidelines for defining an automated zonal application of turbulence closures trained for wake-mixing predictions.


Author(s):  
Behrooz Talaei ◽  
Mohammad Panji ◽  
Fatemeh Nazari Robati ◽  
Sajjad Tezerji

Background: Colorectal cancer is the fourth leading cause of death globally, and the second most common cancer in Europe. About 8% of all cancer-related deaths occur due to colorectal cancer, and the highest prevalence has been reported in Asia and Eastern Europe. Methods: In this experimental study, 80 rats were divided into two groups of cases (n=70) and controls (n=10). Colorectal cancer was induced weekly in rats by subcutaneous injection of 15 mg/kg Azoxymethane. The rats were then divided into 7 experimental subgroups of patients, saline, quercetin, intermittent exercise, continuous exercise, quercetin plus intermittent, and quercetin plus continuous exercise. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured in the rats’ heart tissue by the ELISA method. Data were analyzed using ANOVA by SPSS software. Results: Oxidative stress in heart cells increased due to colorectal cancer. Quercetin alone or in combination with exercise significantly increased mean levels of CAT and SOD in the heart tissue of rats compared with patient and saline groups (P<0.0001). In contrast, the MDA level was significantly decreased (P<0.05). Conclusion: Colorectal cancer increased the oxidative stress in cardiac cells. Quercetin alone improved oxidative stress in cardiac tissue, and its combination with exercise was more effective.


1971 ◽  
Vol 133 (4) ◽  
pp. 677-695 ◽  
Author(s):  
S. P. Halbert ◽  
R. Bruderer ◽  
T. M. Lin

When isolated beating ventricular heart cells from newborn rats were grown in tissue culture on untreated polystyrene surfaces, they showed a striking tendency to grow focally in three dimensions from the single layer cell sheets which were formed early in growth. During this process, they frequently formed miniature spherical heart-like masses, which continued to beat and grow in size. These often were somewhat lobulated in appearance, and grew up to 2 mm in diameter. Histological sections of such structures sometimes revealed evidence of appreciable orientation of the cells to each other, in fiber-like units. Electron microscope sections of such mini-hearts showed structures resembling intercalated discs between myocardial cells. The precise factors which induced the cardiac cells to apparently organize into these heart-like structures are not presently known.


2016 ◽  
Vol 138 (7) ◽  
Author(s):  
Markus Häfele ◽  
Christoph Traxinger ◽  
Marius Grübel ◽  
Markus Schatz ◽  
Damian M. Vogt ◽  
...  

An experimental and numerical study on the flow in a three-stage low-pressure (LP) industrial steam turbine is presented and analyzed. The investigated LP section features conical friction bolts in the last and a lacing wire in the penultimate rotor blade row. These part-span connectors (PSC) allow safe turbine operation over an extremely wide range and even in blade resonance condition. However, additional losses are generated which affect the performance of the turbine. In order to capture the impact of PSCs on the flow field, extensive measurements with pneumatic multihole probes in an industrial steam turbine test rig have been carried out. State-of-the-art three-dimensional computational fluid dynamics (CFD) applying a nonequilibrium steam (NES) model is used to examine the aerothermodynamic effects of PSCs on the wet steam flow. The vortex system in coupled LP steam turbine rotor blading is discussed in this paper. In order to validate the CFD model, a detailed comparison between measurement data and steady-state CFD results is performed for several operating conditions. The investigation shows that the applied one-passage CFD model is able to capture the three-dimensional flow field in LP steam turbine blading with PSC and the total pressure reduction due to the PSC with a generally good agreement to measured values and is therefore sufficient for engineering practice.


2020 ◽  
Vol 494 (4) ◽  
pp. 5360-5373 ◽  
Author(s):  
Rémi Kazeroni ◽  
Ernazar Abdikamalov

ABSTRACT The explosion of massive stars in core-collapse supernovae may be aided by the convective instabilities that develop in their innermost nuclear burning shells. The resulting fluctuations support the explosion by generating additional turbulence behind the supernova shock. It was suggested that the buoyant density perturbations arising from the interaction of the pre-collapse asymmetries with the shock may be the primary contributor to the enhancement of the neutrino-driven turbulent convection in the post-shock region. Employing three-dimensional numerical simulations of a toy model, we investigate the impact of such density perturbations on the post-shock turbulence. We consider a wide range of perturbation parameters. The spatial scale and the amplitude of the perturbations are found to be of comparable importance. The turbulence is particularly enhanced when the perturbation frequency is close to that of the convective turnovers in the gain region. Our analysis confirms that the buoyant density perturbations is indeed the main source of the additional turbulence in the gain region, validating the previous order-of-magnitude estimates.


2021 ◽  
Author(s):  
Aws A. Al-Akam ◽  
Theoklis Nikolaidis ◽  
David G. MacManus ◽  
Alvise Pellegrini

Abstract The use of a simulation tool to predict the aero-engine performance before committing to a final engine design has become one of the most cost-saving approaches in this field. However, most of these tools are based on low fidelity thermodynamic models, which are incapable of fully capturing the impact of three-dimensional flow characteristics. An aero-engine exhaust-system is one of the essential components that affect the engine performance. Currently, engine performance models tend to utilize simplified nozzle performance maps. These maps typically provide information over a very limited range of nozzle geometries, which may not apply to the wide range of architectures and designs of aeroengines. The current paper presents a methodology for the development of nozzle performance maps, which takes into account the aerodynamic and the geometric parameters of the nozzle design. The methodology is based on the reduced-order models. These models are integrated into a zero-dimensional engine performance code to improve the accuracy of its thrust calculation. The impact of the new thrust model on the overall engine performance and the operating point is analysed and discussed. The results showed that the implementation of the modified maps, which take into account the flow characteristics and the geometry of the nozzle, affects the thrust calculation. In a typical case of a turbofan operating at cruise conditions, the net thrust estimation with the modified nozzle maps showed a difference of 0.2%, compared with the simple nozzle maps. The new thrust calculation method has the advantage in capturing the multidimensional impact of the flow of the nozzle as compared with the conventional one. Furthermore, the implementation of the new method reduces the uncertainties introduced by a simplified nozzle model and, consequently, it can support the decision-making process in the design of the engine.


2019 ◽  
Author(s):  
Trisha Lian ◽  
Kevin J. MacKenzie ◽  
David H. Brainard ◽  
Nicolas P. Cottaris ◽  
Brian A. Wandell

Scientists and engineers have created computations and made measurements that characterize the first steps of seeing. ISETBio software integrates such computations and data into an open-source software package. The initial ISETBio implementations modeled image formation (physiological optics) for planar or distant scenes. The ISET3d software described here extends that implementation, simulating image formation for three-dimensional scenes. The software system relies on a quantitative computer graphics program that ray traces the scene radiance through the physiological optics to the retinal irradiance. We describe and validate the implementation for several model eyes. Then, we use the software to quantify the impact of several physiological optics parameters on three-dimensional image formation. ISET3d is integrated with ISETBio, making it straightforward to convert the retinal irradiance into cone excitations. These methods help the user compute the predictions of optics models for a wide range of spatially-rich three-dimensional scenes. They can also be used to evaluate the impact of nearby visual occlusion, the information available to binocular vision, or the retinal images expected from near-field and augmented reality displays.


Sign in / Sign up

Export Citation Format

Share Document