Similar results have been found in allotetraploid Brassica juncea, in which many dominant homoeologs have been found to be related to glucosinolate biosynthesis and to show signs of positive selection.We present what is, to our knowledge, the first chromosome-scale genome assembly for an octoploid strawberry—the highest-level polyploid genome of this quality assembled to date. Analysis of this genome allowed us to identify each of the diploid progenitor species, reconstruct the evolutionary history of the octoploid event, and investigate the evolution of a dominant sub-genome. Our data support the hypothesis that sub-genome dominance in an allopolyploid is established by TE-density differences near homoeologous genes in each of the diploid progenitor genomes. Furthermore, our results show that the F. vesca sub-genome has increased in dominance over time by having retained significantly more ancestral genes and a greater number of tandemly duplicated genes than the other three sub-genomes, and replaced large portions of the submissive sub-genomes via homoeologous exchanges. These trends, combined with sub-genome expression dominance, have resulted in many traits being largely controlled by a single dominant sub-genome in octoploid strawberry. This finding is consistent with results from a recent report indicating that the dominant sub-genome in maize contributes more to phenotypic variation than the submissive sub-genome. This reference genome should serve as a powerful platform for breeders to develop homoeolog-specific markers to track and leverage allelic diversity at target loci.

Thus, we anticipate that this new reference genome, package of blueberries combined with insights into sub-genome dominance, will greatly accelerate molecular breeding efforts in the cultivated garden strawberry.Because exponential growth limits the use of current metallic stents in rapidly growing children, there is a great interest among the pediatric research community for stents that can either grow with an artery or be resorbed1 . Bioresorbable stents have issues related to the effects of their degradation products on the biology of the vessel.Current stents in the market usually require redilation to compensate for somatic growth and to avoid stenosis. We sought to design several self-expanding stents with low crimp profile of <6 Fr and large expanded diameter of 20mm. The designed stents have single row design, with large amplitude, struts with smooth corners and a range of outward radial forces that we predicted to have the ability to adapt their geometries to the potentially large increase in the aortic dimensions over time. This device’s effect on rapidly growing porcine model arteries using quantitative angiography, growth pathology and histopathology was investigated. A description of the designed stent and the effects of its geometry and radial forces on the growing tissue is provided. Approximately 40,000 children in the US are born with a congenital heart deffect annually, with the heart being the most commonly affected organ by birth malformations. It has been estimated that 2.4 million children and adults in the US are currently living with CHD. In particular, coarctation of the aorta affects 4 in 10,000 children born in the US, accounting for 6%–8% of children with CHD. A section of the descending aorta is narrowed in CoA, and this narrowing is usually located at the insertion of the patent ductus arteriosus just distal to the left subclavian artery . 

There are three hypotheses regarding development of CoA:6 First, during development of aortic arch the tissue from the wall of the PDA blends into the tissue of the aorta and when the PDA’s tissue contracts, this blended tissue may also tighten and narrows the aorta and cause the coarctation of the aorta. Second, during fetal life the area between left subclavian artery and the PDA is narrow due to the low blood volume that goes through it. After birth, normal volume of blood flow through the vessel and this area grows. Failure of this phenomenon can lead to formation of CoA. Third, a small segment of the left dorsal aorta could form abnormally. Later, this narrow region moves cranially with left subclavian artery forming CoA. CoA generally results in high ventricle pressure, exertional intolerance, heart failure with or without ventricular dysfunction and has a high morbidity and mortality if untreated. Balloon angioplasty and stenting are the current transcatheter treatments for coarctation of the aorta in children. With a 98% survival rate at a median follow-up of 4.8 years, surgery has been the “gold standard” treatment for infants with coarctation.11 Nonetheless, surgery is associated with numerous risks, including operative and cosmetic morbidities and coarctation reoccurrence. Balloon angioplasty is an accepted technique for infants aged 1–6 months with discrete narrowing; however, this option has been associated with aortic wall damage, restenosis and aneurysm formation. The efficacy of stent implantation in overcoming some of the limitations of balloon dilation has been reported for children more than 3-4 years of age. Forbes et al. reported that stented patients had a significantly lower rate of acute complications than those who underwent surgery and balloon angioplasty. Currently, no balloon-expandable or self expandable stent has been specifically designed for pediatric applications, and patients who receive balloon-expandable stents usually require a planned reintervention owing to the lack of growth in the stents. 

Therefore, a great need for a stent with a capability to self-grow or to be resorbed is warranted. Bioresorbable stents have issues related to the effects of their degradation products on the vasculature so it is reasonable to consider a stent that can “grow with” an artery in a growing child. Although both Zilver stents and Wallstents have been used with some success in the pulmonary arteries of children with congenital heart disease, little is known about the effects of self-expanding stents on growing arteries. Covered thoracic endografts have been previously shown to inhibit aortic growth but uncovered, lower radial force self-expanding stents have never been tested for their ability to grow with an artery. In this study, nitinol self-expanding stents were designed, modeled and manufactured specifically for this application. Four self-expanding stents with a range of outward radial forces were then used to study the effects of stent geometry and force on the biology of rapidly growing arteries in porcine model. A stent is a tubular scaffold device made from either metal, alloy or a polymer that is designed to be inserted into a constricted vessel in different areas of the body to keep the vessel open and restore the flow. Stents come in different material and shape and can be balloon expandable, self-expandable or bioresorbable. Currently there are several different materials for stent making base on the required needs. Stainless steel, platinum-iridium, tantalum, cobaltchromium, superelastic shape-memory alloys , biodegradable polymers and magnesium are to name a few. Each of these materials has a specific constitutive behavior and consequently requires a specific innovation stent design. Super-elasticity and shape-memory are the two characteristics that can be utilized to create a stent that can expand by itself with no external force applied to it . Nitinol is an alloy composed of nickel and titanium. Its corrosion resistance, bio-compatibility, and fatigue resistance, shape memory, and superelasticity behavior makes it a great material for an implant. However, its super elasticity behavior, stress hysteresis, square plant pots and biased stiffness characteristics makes it an ideal material for a self-expandable stent. In the next few sections, we will explain some of Nitinol’s characteristics. Non-elastic material such as stainless steel or cobalt chromium alloy show different elastic deformation behavior compared to living tissue. There is a 1% limit for the strain for elastic deformation of such metals; elongation also increases and decreases linearly with the applied force. However, biological tissue like bone, hair and tendon exhibit more elasticity and deformation, in some cases up to 10% strain in a non-linear way. In these types of materials, the strain is recovered at lower stresses when the deforming stress is releases. Nitinol stress-strain behavior is similar to that of structures in the biological tissue as shown in Figure 1.2 than conventional metal materials. Because deformation of more than 10% strain can be elastically recovered, therefore nitinol can be considered a superelastic material, which makes it an ideal material for a self-growing stent. Biased stiffness is a Nitinol stent feature that results from the stress hysteresis of Nitinol, which plays a crucial rule for making a self-growing stent. This concept is shown in Figure 1.3 and explained below, which demonstrates a schematic super elastic stress-strain curve for a Nitinol stent. This curve has both non-linear response and hysteresis and explains the chronic outward force and radial resistive force of a Nitinol stent, which form the basis for designing a self-growing stent. Using this graph, Stoeckel et al., showed the cycle of crimping a stent into a delivery system, deploying it, and have it expand and interact with the vessel. In this graph, the hoop force represents the stress and stent diameter represent strain. A large diameter stent can be crimped into a small diameter and be loaded into a delivery system to fit into a vessel. Then, by releasing the stent into a vessel, we can make it expand from until the movement is blocked by the vessel diameter . Because the smaller size of the vessel prevents the stent to expand to its full diameter, the stent exerts a low outward force, termed chronic outward force . As shown in Figure 1.3, the chronic outward force stays constant even during the vessel growth and the increase in the vessel’s diameter. If an external force compresses the vessel , the stents resists deformation with a greater force, with forces dictated by the loading curve from point c to d.

In such a way, the stress hysteresis and biased stiffness of Nitinol enables the design of a self-expanding stent, meaning that the stent exerts outward force if it is placed in a small vessel and will expand with the growth of the vessel through exerting constant chronic outward forces and also resists deformation by applying radial resistive force. The intima, the media, and the adventitia are the three different layers of all arteries. As shown in Figure 1.4, the internal elastic lamina separates the intima from the media and the external elastic lamina separates the media from the adventitia. The intima is the most inner layer of the arterial vessel wall, it consist of a layer of endothelial cells which have a direct contact with blood. The media is in the middle between the intima and the adventitia and the adventitia is the outer most layer of the vessel. Each of these three layers have their own function. The intima regulates the active response of the vessel through which pressure regulating agents reach the media, also it can produce nitric oxide to control the vascular tone, which relaxes smooth muscle cells in the media. The media consists of smooth muscle cells that are surrounded by an extracellular plexus of elastin and collagen and an aqueous ground substance that has proteoglycans. The role of the media is to adjust the volume of blood in the vessel by constant constriction and dilations. The outer most layer, the adventitia consists of fibroblasts, connective tissue, and perivascular nerves, and act as a protective sheath, preventing damages of the vessel due to an acute increase in pressure. Contiguous tissue tethering and internal blood flow put a significant mechanical stress on the arteries. Also, if an implant such as a stent is implanted inside the artery, it could alter the biochemical and bio-mechanical properties of the tissue, triggering acute and chronic changes or remolding in the vessel. Many different cell types that reside within the vasculature become involve in the complex and dynamic pathological process of the vascular remodeling. Upon an injury to the arterial vessel wall, the remodeling of the vessel wall can be either constrictive or adaptive as Figure 1.5: Definition of arterial remodeling following injury shows it. Constrictive, inward, or negative remodeling can be accompanied by intimal hyperplasia in a patient with intima damage. Luminal narrowing or stenosis is the direct result of the constrictive remolding or intimal hyperplasia. On the other side, the vessel can go through adaptive, expansive, positive, or outward remodeling which compensate for the formation of the neointima and it is believed to postpone the development of the stenosis, the flow limiting factor. 30 mesenchymal stromal cells reside within the adventitia and other types of cells such as macrophages will migrate and differentiate toward the smooth muscle cells in the intima and contribute to the neointima formation as shown in the Figure 1.6. Aggregation of the neointima in the lumen can restrict the blood flow and cause stenosis.