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Meng-pin Weng - One of the best experts on this subject based on the ideXlab platform.

  • Natural selection drives rapid evolution of mouse Embryonic Heart enhancers
    BMC Systems Biology, 2012
    Co-Authors: Ben-yang Liao, Meng-pin Weng
    Abstract:

    Background Mouse E11.5 Embryonic Heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection.

  • Natural selection drives rapid evolution of mouse Embryonic Heart enhancers
    BMC Systems Biology, 2012
    Co-Authors: Ben-yang Liao, Meng-pin Weng
    Abstract:

    Background Mouse E11.5 Embryonic Heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection. Results In this study, based on the aligned orthologous genomic sequences of mouse and other closely related mammals, the substitution rates of fourfold degenerate sites or intron sequences in neighboring genes were used as neutral references to normalize substitution rates of mouse enhancers. Subsequent comparisons indicated that Heart enhancers' evolutionary rates were increased by natural selection. Correspondingly, the results of Fisher's exact tests to examine the differential enrichment of substitutions between enhancers and neutral sequences suggest that both relaxed purifying selection and positive selection caused the rapid evolution of Heart enhancers. Analyses on recombination rates and substitution patterns indicated that GC-biased gene conversion does not contribute to evolutionary rate variations among enhancers. In general, pleiotropic enhancers and enhancers in proximity to weakly expressed genes, tend to evolve slowly. Although Heart enhancers are less pleiotropic and are adjacent to highly expressed genes, these biases do not account for the rapid evolution observed. Conclusions In combination, the results of the present study suggest that factors associated with functions or characteristics of the tissue may exert direct and profound effects on the intensity and direction of the natural selection applied to regulatory DNAs, such as enhancers.

Irina V Larina - One of the best experts on this subject based on the ideXlab platform.

  • live mechanistic assessment of localized cardiac pumping in mammalian tubular Embryonic Heart
    Journal of Biomedical Optics, 2020
    Co-Authors: Shang Wang, Irina V Larina
    Abstract:

    Significance: Understanding how the valveless Embryonic Heart pumps blood is essential to elucidate biomechanical cues regulating cardiogenesis, which is important for the advancement of congenital Heart defects research. However, methods capable of Embryonic cardiac pumping analysis remain limited, and assessing this highly dynamic process in mammalian embryos is challenging. New approaches are critically needed to address this hurdle. Aim: We report an imaging-based approach for functional assessment of localized pumping dynamics in the early tubular Embryonic mouse Heart. Approach: Four-dimensional optical coherence tomography was used to obtain structural and Doppler hemodynamic imaging of the beating Heart in live mouse embryos at Embryonic day 9.25. The pumping assessment was performed based on the volumetric blood flow rate, flow resistance within the Heart tube, and pressure gradient induced by Heart wall movements. The relation between the blood flow, the pressure gradient, and the resistance to flow were evaluated through temporal analyses and Granger causality test. Results: In the ventricles, our method revealed connections between the temporal profiles of pressure gradient and volumetric blood flow rate. Statistically significant causal relation from the pressure gradient to the blood flow was demonstrated. Our analysis also suggests that cardiac pumping in the early ventricles is a combination of suction and pushing. In contrast, in the outflow tract, where the conduction wave is slower than the blood flow, we did not find significant causal relation from pressure to flow, suggesting that, different from ventricular regions, the local active contraction of the outflow tract is unlikely to drive the flow in that region. Conclusions: We present an imaging-based approach that enables localized assessment of pumping dynamics in the mouse tubular Embryonic Heart. This method creates a new opportunity for functional analysis of the pumping mechanism underlying the developing mammalian Heart at early stages and could be useful for studying biomechanical changes in mutant Embryonic Hearts that model congenital Heart defects.

  • Speckle variance optical coherence tomography of blood flow in the beating mouse Embryonic Heart.
    Journal of biophotonics, 2017
    Co-Authors: Olga A. Grishina, Shang Wang, Irina V Larina
    Abstract:

    Efficient separation of blood and cardiac wall in the beating Embryonic Heart is essential and critical for experiment-based computational modelling and analysis of early-stage cardiac biomechanics. Although speckle variance optical coherence tomography (SV-OCT) relying on calculation of intensity variance over consecutively acquired frames is a powerful approach for segmentation of fluid flow from static tissue, application of this method in the beating Embryonic Heart remains challenging because moving structures generate SV signal indistinguishable from the blood. Here, we demonstrate a modified four-dimensional SV-OCT approach that effectively separates the blood flow from the dynamic Heart wall in the beating mouse Embryonic Heart. The method takes advantage of the periodic motion of the cardiac wall and is based on calculation of the SV signal over the frames corresponding to the same phase of the Heartbeat cycle. Through comparison with Doppler OCT imaging, we validate this speckle-based approach and show advantages in its insensitiveness to the flow direction and velocity as well as reduced influence from the Heart wall movement. This approach has a potential in variety of applications relying on visualization and segmentation of blood flow in periodically moving structures, such as mechanical simulation studies and finite element modelling. Picture: Four-dimensional speckle variance OCT imaging shows the blood flow inside the beating Heart of an E8.5 mouse embryo.

  • Four‐dimensional live imaging of hemodynamics in mammalian Embryonic Heart with Doppler optical coherence tomography
    Journal of Biophotonics, 2016
    Co-Authors: Shang Wang, David S. Lakomy, Monica D. Garcia, Andrew L Lopez, Kirill V. Larin, Irina V Larina
    Abstract:

    Hemodynamic analysis of the mouse Embryonic Heart is essential for understanding the functional aspects of early cardiogenesis and advancing the research in congenital Heart defects. However, high-resolution imaging of cardiac hemodynamics in mammalian models remains challenging, primarily due to the dynamic nature and deep location of the Embryonic Heart. Here we report four-dimensional micro-scale imaging of blood flow in the early mouse Embryonic Heart, enabling time-resolved measurement and analysis of flow velocity throughout the Heart tube. Our method uses Doppler optical coherence tomography in live mouse embryo culture, and employs a post-processing synchronization approach to reconstruct three-dimensional data over time at a 100 Hz volume rate. Experiments were performed on live mouse embryos at Embryonic day 9.0. Our results show blood flow dynamics inside the beating Heart, with the capability for quantitative flow velocity assessment in the primitive atrium, atrioventricular and bulboventricular regions, and bulbus cordis. Combined cardiodynamic and hemodynamic analysis indicates this functional imaging method can be utilized to further investigate the mechanical relationship between blood flow dynamics and cardiac wall movement, bringing new possibilities to study biomechanics in early mammalian cardiogenesis. Four-dimensional live hemodynamic imaging of the mouse Embryonic Heart at Embryonic day 9.0 using Doppler optical coherence tomography, showing directional blood flows in the sinus venosus, primitive atrium, atrioventricular region and vitelline vein.

Ben-yang Liao - One of the best experts on this subject based on the ideXlab platform.

  • Natural selection drives rapid evolution of mouse Embryonic Heart enhancers
    BMC Systems Biology, 2012
    Co-Authors: Ben-yang Liao, Meng-pin Weng
    Abstract:

    Background Mouse E11.5 Embryonic Heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection.

  • Natural selection drives rapid evolution of mouse Embryonic Heart enhancers
    BMC Systems Biology, 2012
    Co-Authors: Ben-yang Liao, Meng-pin Weng
    Abstract:

    Background Mouse E11.5 Embryonic Heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection. Results In this study, based on the aligned orthologous genomic sequences of mouse and other closely related mammals, the substitution rates of fourfold degenerate sites or intron sequences in neighboring genes were used as neutral references to normalize substitution rates of mouse enhancers. Subsequent comparisons indicated that Heart enhancers' evolutionary rates were increased by natural selection. Correspondingly, the results of Fisher's exact tests to examine the differential enrichment of substitutions between enhancers and neutral sequences suggest that both relaxed purifying selection and positive selection caused the rapid evolution of Heart enhancers. Analyses on recombination rates and substitution patterns indicated that GC-biased gene conversion does not contribute to evolutionary rate variations among enhancers. In general, pleiotropic enhancers and enhancers in proximity to weakly expressed genes, tend to evolve slowly. Although Heart enhancers are less pleiotropic and are adjacent to highly expressed genes, these biases do not account for the rapid evolution observed. Conclusions In combination, the results of the present study suggest that factors associated with functions or characteristics of the tissue may exert direct and profound effects on the intensity and direction of the natural selection applied to regulatory DNAs, such as enhancers.

David Elad - One of the best experts on this subject based on the ideXlab platform.

  • the driving mechanism for unidirectional blood flow in the tubular Embryonic Heart
    Annals of Biomedical Engineering, 2016
    Co-Authors: Pavel Kozlovsky, Robert J Brysonrichardson, A J Jaffa, Moshe Rosenfeld, David Elad
    Abstract:

    The Embryonic Heart of vertebrate embryos, including humans, has a tubular thick-wall structure when it first starts to beat. The tubular Embryonic Heart (TEH) does not have valves, and yet, it produces an effective unidirectional blood flow. The actual pumping mechanism of the TEH is still controversial with pros and cons for either peristaltic pumping (PP) or impedance pumping (IP). On the other hand, observation of movies of the contractile TEH of the quail revealed a propagating wave from the venous end towards the arterial end that occludes the lumen behind the leading edge. This pattern of contraction represents a complex PP with a duty cycle, and was defined here as biological pumping (BP). In this work we developed a Heart-like model that represents the main features of the chick TEH and allows for numerical analysis of all the three pumping mechanisms (i.e., IP, PP, and BP) as well as a comprehensive sensitivity evaluation of the structural, operating, and mechanical parameters. The physical model also included components representing the whole circulatory system of the TEH. The simulations results revealed that the BP mechanism yielded the level and time-dependent pattern of blood flow and blood pressure, as well as contractility that were observed in experiments.

A J Jaffa - One of the best experts on this subject based on the ideXlab platform.

  • the driving mechanism for unidirectional blood flow in the tubular Embryonic Heart
    Annals of Biomedical Engineering, 2016
    Co-Authors: Pavel Kozlovsky, Robert J Brysonrichardson, A J Jaffa, Moshe Rosenfeld, David Elad
    Abstract:

    The Embryonic Heart of vertebrate embryos, including humans, has a tubular thick-wall structure when it first starts to beat. The tubular Embryonic Heart (TEH) does not have valves, and yet, it produces an effective unidirectional blood flow. The actual pumping mechanism of the TEH is still controversial with pros and cons for either peristaltic pumping (PP) or impedance pumping (IP). On the other hand, observation of movies of the contractile TEH of the quail revealed a propagating wave from the venous end towards the arterial end that occludes the lumen behind the leading edge. This pattern of contraction represents a complex PP with a duty cycle, and was defined here as biological pumping (BP). In this work we developed a Heart-like model that represents the main features of the chick TEH and allows for numerical analysis of all the three pumping mechanisms (i.e., IP, PP, and BP) as well as a comprehensive sensitivity evaluation of the structural, operating, and mechanical parameters. The physical model also included components representing the whole circulatory system of the TEH. The simulations results revealed that the BP mechanism yielded the level and time-dependent pattern of blood flow and blood pressure, as well as contractility that were observed in experiments.