TAD evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function.

Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation.

Energetics of Cardiac Blood Flow in Hypertrophic Cardiomyopathy through Individualized Computational Modeling.

Hypertrophic cardiomyopathy (HCM) is a congenital heart disease characterized by thickening of the heart's left ventricle (LV) wall that can lead to cardiac dysfunction and heart failure. Ventricular wall thickening affects the motion of cardiac walls and blood flow within the heart. Because abnormal cardiac blood flow in turn could lead to detrimental remodeling of heart walls, aberrant ventricular flow patterns could exacerbate HCM progression.

Coaxial Placement of Balloon-Expandable and Self-Expanding Stents: Impact on Crush Resistance and Luminal Recovery in a Benchtop Model.

During endovascular interventions, coaxial deployment of stents may be required to preserve luminal gain. This study characterized in vitro the effect on crush resistance and postcompression recovery when 316L stainless steel balloon-expandable (BE) and laser-cut nitinol self-expanding (SE) venous stents were deployed coaxially. Various stent configurations were parallel-plate compressed from a fully expanded state to 50% diameter reduction (Criterion, Model 42; MTS, Eden Prairie, Minnesota) in a 37 °C ± 1 water bath.

TAD Evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function.

Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species, and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation.

Effect of Blood Flow on Cardiac Morphogenesis and Formation of Congenital Heart Defects.

Congenital heart disease (CHD) affects about 1 in 100 newborns and its causes are multifactorial. In the embryo, blood flow within the heart and vasculature is essential for proper heart development, with abnormal blood flow leading to CHD. Here, we discuss how blood flow (hemodynamics) affects heart development from embryonic to fetal stages, and how abnormal blood flow solely can lead to CHD.

Impact of Postthrombotic Vein Wall Biomechanics on Luminal Flow during Venous Angioplasty and Stent Placement: Computational Modeling Results.

This study characterized the impact of vein wall biomechanics on inflow diameter and luminal flow during venous angioplasty and stent placement, using postthrombotic and healthy biomechanical properties from an ovine venous stenosis and thrombosis model. Finite element analysis demonstrated more pronounced inflow channel narrowing in the postthrombotic vein compared with the healthy control vein during angioplasty and stent placement (relative inflow diameter reduction of 42% versus 13%, P < .0001).

Dipeptidyl peptidase IV inhibition delays developmental programming of obesity and metabolic disease in male offspring of obese mothers.

Maternal obesity programs the offspring to metabolic diseases later in life; however, the mechanisms of programming are yet unclear, and no strategies exist for addressing its detrimental transgenerational effects. Obesity has been linked to dipeptidyl peptidase IV (DPPIV), an adipokine, and treatment of obese individuals with DPPIV inhibitors has been reported to prevent weight gain and improve metabolism. We hypothesized that DPPIV plays a role in maternal obesity-mediated programming.

Endovascular Venous Stenosis and Thrombosis Large Animal Model: Angiographic, Histological, and Biomechanical Characterizations.

Purpose: To characterize an ovine endovascular radiofrequency (RF) ablation-based venous stenosis and thrombosis model for studying venous biomechanics and response to intervention.

Materials And Methods: Unilateral short-segment (n = 2) or long-segment (n = 6) iliac vein stenoses were created in 8 adult sheep using an endovenous RF ablation technique. Angiographic assessment was performed at baseline, immediately after venous stenosis creation, and after 2-week (n = 6) or 3-month (n = 2) survival.

Preclinical therapeutics ex ovo quail eggs as a biomimetic automation-ready xenograft platform.

Preclinical cancer research ranges from in vitro studies that are inexpensive and not necessarily reflective of the tumor microenvironment to mouse studies that are better models but prohibitively expensive at scale. Chorioallantoic membrane (CAM) assays utilizing Japanese quail (Coturnix japonica) are a cost-effective screening method to precede and minimize the scope of murine studies for anti-cancer efficacy and drug toxicity. To increase the throughput of CAM assays we have built and optimized an 11-day platform for processing up to 200 quail eggs per screening to evaluate drug efficacy and drug toxicity caused by a therapeutic.

Patient-specific computational modeling of endovascular aneurysm repair: State of the art and future directions.

Endovascular aortic repair (EVAR) has become the preferred intervention option for aortic aneurysms and dissections. This is because EVAR is much less invasive than the alternative open surgery repair. While in-hospital mortality rates are smaller for EVAR than open repair (1%-2% vs.

Fetal Blood Flow and Genetic Mutations in Conotruncal Congenital Heart Disease.

In congenital heart disease, the presence of structural defects affects blood flow in the heart and circulation. However, because the fetal circulation bypasses the lungs, fetuses with cyanotic heart defects can survive in utero but need prompt intervention to survive after birth. Tetralogy of Fallot and persistent truncus arteriosus are two of the most significant conotruncal heart defects.

Transient increase in VEGF-A leads to cardiac tube anomalies and increased risk of congenital heart malformations.

Vascular endothelial growth factor (VEGF) plays a critical role during early heart development. Clinical evidence shows that conditions associated with changes in VEGF signaling in utero are correlated with an increased risk of congenital heart defects (CHD) in newborns. However, how malformations develop after abnormal VEGF exposure is unknown.

Multiscale cardiac imaging spanning the whole heart and its internal cellular architecture in a small animal model.

Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three-dimensional (3D) heart structure, to assess malformations; and its ultrastructure, to assess organelle disruptions.

Few-shot hypercolumn-based mitochondria segmentation in cardiac and outer hair cells in focused ion beam-scanning electron microscopy (FIB-SEM) data.

We present a novel AI-based approach to the few-shot automated segmentation of mitochondria in large-scale electron microscopy images. Our framework leverages convolutional features from a pre-trained deep multilayer convolutional neural network, such as VGG-16. We then train a binary gradient boosting classifier on the resulting high-dimensional feature hypercolumns.

Predictors of Abdominal Aortic Aneurysm Risks.

Computational biomechanics via finite element analysis (FEA) has long promised a means of assessing patient-specific abdominal aortic aneurysm (AAA) rupture risk with greater efficacy than current clinically used size-based criteria. The pursuit stems from the notion that AAA rupture occurs when wall stress exceeds wall strength. Quantification of peak (maximum) wall stress (PWS) has been at the cornerstone of this research, with numerous studies having demonstrated that PWS better differentiates ruptured AAAs from non-ruptured AAAs.

Venous Biomechanics of Angioplasty and Stent Placement: Implications of the Poisson Effect.

Purpose: To characterize the Poisson effect in response to angioplasty and stent placement in veins and identify potential implications for guiding future venous-specific device design.

Materials And Methods: In vivo angioplasty and stent placement were performed in 3 adult swine by using an established venous stenosis model. Iron particle endothelium labeling was performed for real-time fluoroscopic tracking of the vessel wall during intervention.

Follow Me! A Tale of Avian Heart Development with Comparisons to Mammal Heart Development.

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can then be covered, and the embryo returned to the incubator for the desired amount of time, and observed during further development.

Optical coherence tomography for imaging of endocardial to mesenchymal transition during avian heart development.

The endocardial to mesenchymal transition (EndMT) that occurs in endocardial cushions during heart development is critical for proper heart septation and formation of the heart's valves. In EndMT, cells delaminate from the endocardium and migrate into the previously acellular endocardial cushions. Optical coherence tomography (OCT) imaging uses the optical properties of tissues for contrast, and during early development OCT can differentiate cellular versus acellular tissues.

4-D Computational Modeling of Cardiac Outflow Tract Hemodynamics over Looping Developmental Stages in Chicken Embryos.

Cardiogenesis is interdependent with blood flow within the embryonic system. Recently, a number of studies have begun to elucidate the effects of hemodynamic forces acting upon and within cells as the cardiovascular system begins to develop. Changes in flow are picked up by mechanosensors in endocardial cells exposed to wall shear stress (the tangential force exerted by blood flow) and by myocardial and mesenchymal cells exposed to cyclic strain (deformation).

Light-sheet Fluorescence Microscopy for the Study of the Murine Heart.

Light-sheet fluorescence microscopy has been widely used for rapid image acquisition with a high axial resolution from micrometer to millimeter scale. Traditional light-sheet techniques involve the use of a single illumination beam directed orthogonally at sample tissue. Images of large samples that are produced using a single illumination beam contain stripes or artifacts and suffer from a reduced resolution due to the scattering and absorption of light by the tissue.

Quantifying blood flow dynamics during cardiac development: demystifying computational methods.

Blood flow conditions (haemodynamics) are crucial for proper cardiovascular development. Indeed, blood flow induces biomechanical adaptations and mechanotransduction signalling that influence cardiovascular growth and development during embryonic stages and beyond. Altered blood flow conditions are a hallmark of congenital heart disease, and disrupted blood flow at early embryonic stages is known to lead to congenital heart malformations.

Influence of blood flow on cardiac development.

The role of hemodynamics in cardiovascular development is not well understood. Indeed, it would be remarkable if it were, given the dauntingly complex array of intricately synchronized genetic, molecular, mechanical, and environmental factors at play. However, with congenital heart defects affecting around 1 in 100 human births, and numerous studies pointing to hemodynamics as a factor in cardiovascular morphogenesis, this is not an area in which we can afford to remain in the dark.

Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart.

Congenital heart defects (CHDs) represent the most common form of human birth defects; approximately one-third of heart defects involve malformations of the outflow tract (OFT). Maternal diabetes increases the risk of CHD by 3-5 fold. During heart organogenesis, little is known about the effects of hyperglycemia on hemodynamics, which are critical to normal heart development.

Hemodynamics Modify Collagen Deposition in the Early Embryonic Chicken Heart Outflow Tract.

Blood flow is critical for normal cardiac development. Hemodynamic stimuli outside of normal ranges can lead to overt cardiac defects, but how early heart tissue remodels in response to altered hemodynamics is poorly understood. This study investigated changes in tissue collagen in response to hemodynamic overload in the chicken embryonic heart outflow tract (OFT) during tubular heart stages (HH18 to HH24, ~24 h).

Intraluminal thrombus is associated with early rupture of abdominal aortic aneurysm.

Background: The implications of intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) are currently unclear. Previous studies have demonstrated that ILT provides a biomechanical advantage by decreasing wall stress, whereas other studies have associated ILT with aortic wall weakening. It is further unclear why some aneurysms rupture at much smaller diameters than others.