Aortic dissection is the most common acute catastrophic event affecting the thoracic aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent aneurysmal dilatation of the thoracic aorta. This study aimed at gaining more detailed knowledge of the flow phenomena associated with this condition. Morphological features and flow patterns in a dissected aortic segment of a presurgery type B dissection patient were analyzed based on computed tomography images acquired from the patient. Computational simulations of blood flow in the patient-specific model were performed by employing a correlation-based transitional version of Menter's hybrid k-epsilon/k-omega shear stress transport turbulence model implemented in ANSYS CFX 11. Our results show that the dissected aorta is dominated by locally highly disturbed, and possibly turbulent, flow with strong recirculation. A significant proportion (about 80%) of the aortic flow enters the false lumen, which may further increase the dilatation of the aorta. High values of wall shear stress have been found around the tear on the true lumen wall, perhaps increasing the likelihood of expanding the tear. Turbulence intensity in the tear region reaches a maximum of 70% at midsystolic deceleration phase. Incorporating the non-Newtonian behavior of blood into the same transitional flow model has yielded a slightly lower peak wall shear stress and higher maximum turbulence intensity without causing discernible changes to the distribution patterns. Comparisons between the laminar and turbulent flow simulations show a qualitatively similar distribution of wall shear stress but a significantly higher magnitude with the transitional turbulence model.
Aortic dissection causes splitting of the aortic wall layers, allowing blood to enter a ‘false lumen’ (FL). For type B dissection, a significant predictor of patient outcomes is patency or thrombosis of the FL. Yet, no methods are currently available to assess the chances of FL thrombosis. In this study, we present a new computational model that is capable of predicting thrombus formation, growth and its effects on blood flow under physiological conditions. Predictions of thrombus formation and growth are based on fluid shear rate, residence time and platelet distribution, which are evaluated through convection–diffusion–reaction transport equations. The model is applied to a patient-specific type B dissection for which multiple follow-up scans are available. The predicted thrombus formation and growth patterns are in good qualitative agreement with clinical data, demonstrating the potential applicability of the model in predicting FL thrombosis for individual patients. Our results show that the extent and location of thrombosis are strongly influenced by aortic dissection geometry that may change over time. The high computational efficiency of our model makes it feasible for clinical applications. By predicting which aortic dissection patient is more likely to develop FL thrombosis, the model has great potential to be used as part of a clinical decision-making tool to assess the need for early endovascular intervention for individual dissection patients.
Summary
The tetrapyrroles heme, bacteriochlorophyll and cobalamin (B12) exhibit a complex interrelationship regarding their synthesis. In this study, we demonstrate that AerR functions as an antirepressor of the tetrapyrrole regulator CrtJ. We show that purified AerR contains B12 that is bound to a conserved histidine (His145) in AerR. The interaction of AerR to CrtJ was further demonstrated in vitro by pull down experiments using AerR as bait and quantified using microscale thermophoresis. DNase I DNA footprint assays show that AerR containing B12 inhibits CrtJ binding to the bchC promoter. We further show that bchC expression is greatly repressed in a B12 auxotroph of Rhodobacter capsulatus and that B12 regulation of gene expression is mediated by AerR’s ability to function as an antirepressor of CrtJ. This study thus provides a mechanism for how the essential tetrapyrrole, cobalamin controls the synthesis of bacteriochlorophyll, an essential component of the photosystem.
Lantibiotics are a type of ribosomally synthesized and post‐translationally modified peptides (termed lanthipeptides) with often potent antimicrobial activity. Herein, we report the discovery of a new lantibiotic, lexapeptide, using the library expression analysis system (LEXAS) approach. Lexapeptide has rare structural modifications, including N‐terminal (N,N)‐dimethyl phenylalanine, C‐terminal (2‐aminovinyl)‐3‐methyl‐cysteine, and d‐Ala. The characteristic lanthionine moiety in lexapeptide is formed by three proteins (LxmK, LxmX, and LxmY), which are distinct from enzymes known to be involved in lanthipeptide biosynthesis. Furthermore, a novel F420H2‐dependent reductase (LxmJ) from the lexapeptide biosynthetic gene cluster (BGC) is identified to catalyze the reduction of dehydroalanine to install d‐Ala. Our findings suggest that lexapeptide is the founding member of a new class of lanthipeptides that we designate as class V. We also identified further class V lanthipeptide BGCs in actinomycetes and cyanobacteria genomes, implying that other class V lantibiotics await discovery.
Results obtained from this preliminary work suggest that aortic morphology and primary entry tear size and position exert significant effects on flow and other hemodynamic parameters in the dissected aorta in this preliminary work. Blood flow into the false lumen increases with increasing tear size and proximal location. Morphologic analysis coupled with computational fluid dynamic modeling may be useful in predicting acute type B dissection behavior allowing for selection of proper treatment modalities, and further confirmatory studies are warranted.
These preliminary observations point to a potential link between high wall stress and accelerated metabolism in aortic aneurysm wall and warrant further large population-based studies.
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