scholarly journals Multiscale model of heart growth during pregnancy: Integrating mechanical and hormonal signaling

2020 ◽  
Author(s):  
Kyoko Yoshida ◽  
Jeffrey J. Saucerman ◽  
Jeffrey W. Holmes

AbstractPregnancy stands at the interface of mechanics and biology. The growing fetus continuously loads the maternal organs as circulating hormone levels surge, leading to significant changes in mechanical and hormonal cues during pregnancy. In response to these cues, maternal soft tissues undergo remarkable growth and remodeling to support both mother and baby for a healthy pregnancy. We focus here on the maternal left ventricle, which increases its cardiac output and mass during pregnancy. The objective of this study is to build a multiscale cardiac growth model for pregnancy to understand how mechanical and hormonal cues interact to drive this growth process. Towards this objective, we coupled a cell signaling network model that predicts cell-level hypertrophy in response to hormones and stretch, to a compartmental model of the rat heart and circulation that predicts organ-level growth in response to hemodynamic changes. Since pregnancy is associated with a volume overloaded state and elevated hormones, we first calibrated the coupled, multiscale model to data from experimental volume overload (VO) and hormonal infusion of angiotensin 2 (AngII), estrogen (E2), and progesterone (P4). We then validated the ability of our model to capture interactions between inputs by comparing model predictions against published observations for the combinations of VO+E2 and AngII+E2. Finally, we simulated pregnancy-induced changes in hormones and hemodynamics to predict heart growth during pregnancy. Our multiscale model produced realistic heart growth consistent with experimental data. Overall, our analysis suggests that much of heart growth during pregnancy is driven by the early rise in P4, particularly during the first half of gestation. We conclude with suggestions for future experimental studies that will provide a better understanding of how hormonal and mechanical cues interact to drive pregnancy-induced heart growth.

Author(s):  
Victor K. Lai ◽  
Mohammad F. Hadi ◽  
Robert T. Tranquillo ◽  
Victor H. Barocas

In addition to their obvious biological roles in tissue function, cells often play a significant mechanical role through a combination of passive and active behaviors. Phenomenological and continuum modeling approaches to understand tissue biomechanics have included improved constitutive laws that incorporate anisotropy in the extracellular matrix (ECM) and/or cellular phenomenon, e.g, [1]. The lack of microstructural detail in these models, however, limits their ability to explore the respective contributions and interactions between different components within a tissue. In contrast, structural approaches attempt to understand tissue biomechanics by incorporating microstructural details directly into the model, e.g., the tensegrity model [2], cellular solids models [3], or biopolymer models [4]. Research in our group focuses on developing a comprehensive model to predict the mechanical behavior of soft tissues via a multiscale approach, a technique that allows integration of the microstructural details of different components into the modeling framework. A significant gap in our previous models, however, is the absence of cells. The current work represents an improvement of the multiscale model via the addition of cells, and investigates the passive mechanical contribution of cells to overall tissue mechanics.


1996 ◽  
Vol 118 (4) ◽  
pp. 214-222 ◽  
Author(s):  
T. E. Voth ◽  
T. L. Bergman

The thermomechanical response of ball-grid array assemblies during reflow soldering is considered here. Experiments are performed to investigate the thermomechanical response of a representative system and the results are used to validate a numerical model of system behavior. The conclusions drawn from the experimental studies are used to guide development of a process model capable of describing more realistic BGA soldering scenarios. Process model predictions illustrate the system’s thermomechanical response to thermal and mechanical processing conditions, as well as component properties. High thermal conductivity assemblies show the greatest sensitivity to mechanical loading conditions.


2012 ◽  
Vol 153 (6) ◽  
pp. 214-221 ◽  
Author(s):  
Veronika Urbán S. ◽  
Elizabeta Benevolenskaya ◽  
Judit Kiss ◽  
Bernadett Sági ◽  
Beáta Hegyi ◽  
...  

Analysis of genomic sequences has clearly shown that the genomic differences among species do not explain the diversity of life. The genetic code itself serves as only a part of the dynamic complexity that results in the temporal and spatial changes in cell phenotypes during development. It has been concluded that the phenotype of a cell and of the organism as a whole is more influenced by environmentally-induced changes in gene activity than had been previously thought. The emerging field of epigenetics focuses on molecular marks on chromatin; called the epigenome, which serve as transmitters between the genome and the environment. These changes not only persist through multiple cell division cycles, but may also endure for multiple generations. Irregular alterations of the epigenome; called epimutations, may have a decisive role in the etiology of human pathologies such as malignancies and other complex human diseases. Epigenetics can provide the missing link between genetics, disease and the environment. Therefore, this field may have an increasing impact on future drug design and serve as a basis for new therapeutic/preventative approaches. Orv. Hetil., 2012, 153, 214–221.


1976 ◽  
Vol 21 (3) ◽  
pp. 563-578
Author(s):  
J.H. Temmink ◽  
J.G. Collard ◽  
J. Roosien ◽  
J.F. Van den Bosch

Two human lymphoblasts (Raji and EB3) and normal human peripheral lymphocytes were exposed to different concentrations of Concanavalin A and wheat germ agglutinin. The lectin-induced agglutination was determined and correlated with lectin-induced changes in the surface morphology of these cells as studied in a scanning electron microscope. Whenever the lectin induced high agglutinability in a cell type, it also invariably had a smoothing effect on the cell surface. In contrast, when cells did not agglutinate well with a certain lectin, their cell surface remained essentially rough (villous) after addition of the lectin. The correlation found between increased agglutinability and altered cell surface morphology upon treatment with certain lectins suggests that both phenomena result from one and the same process. Additional evidence for this postulate is presented.


2021 ◽  
Vol 2057 (1) ◽  
pp. 012041
Author(s):  
V I Valiullina ◽  
A I Mullayanov ◽  
A A Musin ◽  
L A Kovaleva

Abstract Experimental studies of the gravitational deposition of a polydisperse water-in-oil emulsion under heat influence are carried out. When the rate of thermal convection exceeds the rate of precipitation, partial delamination of the emulsion is found to occur. The viscosity of the dispersion medium decreases with increasing temperature, which contributes to an increase in the deposition rate of water droplets in the emulsion. In the presence of a temperature difference, convective flows occur in the liquid, while the drops of the emulsion coagulate and form larger agglomerates that settle faster to the bottom of the cell.


2019 ◽  
Vol 9 (12) ◽  
pp. 358 ◽  
Author(s):  
Tatullo ◽  
Codispoti ◽  
Spagnuolo ◽  
Zavan

Promising researches have demonstrated that the alteration of biological rhythms may be consistently linked to neurodegenerative pathologies. Parkinson’s disease (PD) has a multifactorial pathogenesis, involving both genetic and environmental and/or molecular co-factors. Generally, heterogeneous alterations in circadian rhythm (CR) are a typical finding in degenerative processes, such as cell aging and death. Although numerous genetic phenotypes have been discovered in the most common forms of PD, it seems that severe deficiencies in synaptic transmission and high vesicular recycling are frequently found in PD patients. Neuron-to-neuron interactions are often ensured by exosomes, a specific type of extracellular vesicle (EV). Neuron-derived exosomes may carry several active compounds, including miRNAs: Several studies have found that circulating miRNAs are closely associated with an atypical oscillation of circadian rhythm genes, and they are also involved in the regulation of clock genes, in animal models. In this context, a careful analysis of neural-differentiated Mesenchymal Stem Cells (MSCs) and the molecular and genetic characterization of their exosome content, both in healthy cells and in PD-induced cells, could be a strategic field of investigation for early diagnosis and better treatment of PD and similar neurodegenerative pathologies. A novel MSC population, called human periapical cyst–mesenchymal stem cells (hPCy–MSCs), has demonstrated that it naively expresswa the main neuronal markers, and may differentiate towards functional neurons. Therefore, hPCy–MSCs can be considered of particular interest for testing of in vitro strategies to treat neurological diseases. On the other hand, the limitations of using stem cells is an issue that leads researchers to perform experimental studies on the exosomes released by MCSs. Human periapical cyst-derived mesenkymal stem cells can be a smart “lab-on-a-cell” to investigate neurodegenerative diseases and the related exosomes’ content alteration.


Author(s):  
T H C Childs ◽  
S Mahmood ◽  
H J Yoon

Recently a new process known as magnetic fluid grinding has been developed in Japan which can remove material in the finishing of ceramic balls some fifty times more rapidly than can the lapping processes that are conventionally used. Balls are driven round a cell by a rotating shaft in an arrangement similar to a thrust race but submerged in a magnetic fluid placed above permanent magnets. The magnets and fluid create buoyancy forces that levitate grinding grits in the fluid and also provide the loads for the process, but it is not clear why the process is more effective than lapping. This paper reports on experimental studies of the grinding rates of silicon nitride balls in magnetic fluids loaded with diamond grits and of the motion of the balls through the fluids. The high removal rates occur when skidding occurs between the balls and drive shaft. A kinematic theory is developed to calculate sliding speeds and is used to deduce an abrasive wear coefficient for the process of 0.07 ± 0.02, indicative of two-body abrasion. The high removal rates are a consequence of the large sliding speeds that can be developed, of several metres per second.


Author(s):  
Nathan T. Jacobs ◽  
Daniel H. Cortes ◽  
Spencer E. Szczesny ◽  
Edward J. Vresilovic ◽  
Dawn M. Elliott

Tissue modeling requires an appropriate stress-strain constitutive relationship and a corresponding set of material properties. It is often the goal of experimental studies to determine these material properties. Uniaxial tension experiments are simple in experimental approach and the interpretation of results is straightforward, prompting its use in several studies. However, the freely contracting lateral edges observed in this loading modality do not mimic the in situ conditions of many fiber-reinforced soft tissues and the unconstrained fibers may also create errors.


Author(s):  
Meryem Kanzari ◽  
Mohammed AlQaradawi ◽  
Balakumar Balachandran

Flexible, rotating structures can experience complex dynamics, when torsional and lateral motions are involved. Oilwell drill strings form one example of such structures. In the present study, the authors investigate the influence of sinusoidal drive speed modulation on whirling motions of flexible rotors with contact interactions. For two types of drilling-like operations, one with drill mud and another without drill mud, the stability of motions is studied. A laboratory-scale drill rig is used to study the dynamics of a flexible rotor, which is driven at one end and housed within a stator at the other end. Experimental results are presented and discussed for different drive speeds. The findings suggest that the addition of drill mud in the annular space between the rotor and stator along with high-frequency modulation in the drive input helps attenuate lateral motions. The torsional motions appear to be influenced more by the high-frequency drive speed modulation. A three-degree-of-freedom model has been constructed to study lateraltorsional dynamics of a rotor-stator system. The model predictions are compared with the experimental data. The findings of this work have relevance for constructing practical solutions to control whirl dynamics of flexible rotors such as drill strings.


2004 ◽  
Vol 78 (11) ◽  
pp. 5799-5804 ◽  
Author(s):  
Isabel S. Novella ◽  
Daniel D. Reissig ◽  
Claus O. Wilke

ABSTRACT We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its wild-type ancestor. We carried out competitions of MARM N and wild-type populations at different multiplicities of infection (MOIs) and initial ratios of the wild type to the mutant and found that the fitness of MARM N relative to that of the wild type is very sensitive to changes in the MOI (i.e., the degree of complementation) but depends little, if at all, on the initial frequencies of MARM N and the wild type. Further, we developed a mathematical model under the assumption that during coinfection both viruses contribute to a common pool of protein products in the infected cell and that they both exploit this common pool equally. Under such conditions, the fitness of all virions that coinfect a cell is the average fitness in the absence of coinfection of that group of virions. In the absence of coinfection, complementation cannot take place and the relative fitness of each competitor is only determined by the selective value of its own products. We found good agreement between our experimental results and the model predictions, which suggests that the wild type and MARM N freely share all of their gene products under coinfection.


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