Incidence and type of bicuspid aortic valve in two model species

Incidence and type of bicuspid aortic valve in two model species. MC Fernández 1,2, A López-García 1,2, MT Soto 1, AC Durán 1,2 and B Fernández 1,2. 1 Department of Animal Biology, Faculty of Science, University of Málaga, Spain. 2 Biomedical Research Institute of Málaga (IBIMA), University of Málaga, Spain. Bicuspid aortic valve (BAV) is the most frequent human congenital cardiac malformation, with an incidence of 1–2% worldwide. Two morphological types exist: type A (incidence 0.75–1.25%) and type B (incidence 0.25–0.5%), each with a distinct aetiology and natural history. Currently, ten animal models of BAV have been described in two different rodent species: one spontaneous Syrian hamster (Mesocricetus auratus) model of BAV type A and nine mutant laboratory mouse (Mus musculus) models of BAV type B. It remains to be elucidated whether the mutations leading to BAV in these models are typespecific or whether there are inter-specific differences regarding the type of BAV that hamsters, mice and humans may develop. To solve this issue, we have characterized the incidence and types of BAVs in four inbred, two outbred and two hybrid lines of Syrian hamsters (n=4,340) and in three inbred, three outbred and one hybrid lines of laboratory mice (n=1,661) by means of stereomicroscopy and scanning electron microscopy. In addition, we have reviewed and calculated the incidence and type of BAVs in the published papers dealing with this anomaly in mice. Our results indicate that the Syrian hamster develops BAVs type A and B including a variety of morphologies comparable to those of humans, whereas the mouse develops only BAVs type B with a short spectrum of valve morphologies. Thus, inter-specific differences between human and mouse aortic valves must be taken into consideration when studying valve disease in murine models. This work was supported by P10-CTS-6068.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. P10-CTS-6068

The Ultraviolet Luminosity Density of the Universe from Photometric Redshifts of Galaxies in the Hubble Deep Field

Studies of the Hubble Deep Field (HDF) and other deep surveys have revealed an apparent peak in the ultraviolet (UV) luminosity density, and therefore the star-formation rate density, of the Universe at redshifts 1<z<2. We use photometric redshifts of galaxies in the HDF to determine the comoving UV luminosity density and find that, when errors (in particular, sampling error) are properly accounted for, a flat distribution is statistically indistinguishable from a distribution peaked at z~1.5. Furthermore, we examine the effects of cosmological surface brightness (SB) dimming on these measurements by applying a uniform SB cut to all galaxy fluxes after correcting them to redshift z=5. We find that, comparing all galaxies at the same intrinsic surface brightness sensitivity, the UV luminosity density contributed by high intrinsic SB regions increases by almost two orders of magnitude from z~0 to z~5. This suggests that there exists a population of objects with very high star formation rates at high redshifts that apparently do not exist at low redshifts. The peak of star formation, then, may occur somewhere beyond a redshift z~>5.Comment: 4 pages total, including 3 embedded figures, to appear in the proceedings of the Xth Rencontres de Blois, "The Birth of Galaxies." LaTeX style file include

Endocardial-mesenchymal transition underlies fusion of the conotruncal ridges during embryonic cardiac outflow tract septation

The embryonic cardiac outflow tract (conotruncus) is a single tubular chamber that connects the right ventricle with the aortic arch arteries. It contains two opposite, long and helical mesenchymal cushions covered by endocardial cells (conotruncal ridges). Conotruncal division (septation) gives rise to the adult right and left outflows together with the aortic and pulmonary valves. It takes place by fusion of the two opposite ridges and formation of the conotruncal septum. Although the participation of neural crest cells in septation is well established, the mechanism of fusion of the conotruncal ridges remains unknown. Defects in fusion have been shown to produce bicuspid aortic valve, the most prevalent human congenital cardiac malformation, in a hamster model. Three fusion mechanisms have been proposed to operate during embryonic development: epithelial adhesion, epithelial apoptosis and epithelial-mesenchymal transition (EMT). The first mechanism entails the expression of adhesion molecules and the maintenance of the identity of cells in contact, whereas in the other two, epithelial cells covering the fusing structures disappear by apoptosis or by transforming into mesenchymal cells. The objective of this study is to elucidate the mechanism involved in the fusion of the conotruncal ridges. Immunofluorecence techniques were used in ED 11-12 hamster embryos. The results indicate that the mechanism of EMT, but not epithelial adhesion or apoptosis, is involved in the process of fusion of the conotruncal ridges. The EMT mechanism associated with conotruncal septation seems to be uncoupled from the process of formation of the endocardial cushions, which takes place at early stages. With these results, we can raise the hypothesis that defects in the EMT process may lead to different morphological types of bicuspid aortic valve.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This study was supported by P10-CTS-6068 (Junta de Andalucía), CGL2014-52356-P and CGL2017-85090-P (Ministerio de Economía y Competitividad), contract UMAJI75 (Junta de Andalucía, European Social Fund), and Universidad de Málaga

Effect of hyperlipidic diets on normal and abnormal aortic valves in the Syrian hamster: A preliminary study

Effect of hyperlipidic diets on normal and abnormal aortic valves in the Syrian hamster: A preliminary study. MC Fernández 1,2, J Moncayo-Arlandi 1, MT Soto 1, MA López-Unzu 1, B Fernández 1,2 and AC Durán 1,2. 1 Department of Animal Biology, Faculty of Science, University of Málaga, Spain. 2 Biomedical Research Institute of Málaga (IBIMA), University of Málaga, Spain. Bicuspid aortic valve (BAV) is the most frequent human congenital cardiac malformation. It frequently becomes stenotic due to calcification by an atherosclerosis-like process. Hyperlipidic diets have been classically used to induce atherosclerosis in laboratory animals, including Syrian hamsters. The aim here is to evaluate the effect of hyperlipidic diets in hamsters having different incidence of BAVs. We used a unique inbred strain of Syrian hamsters with a high ( 40%) incidence of spontaneous BAV, morphologically similar to that in man, another inbred strain with a low ( 4%) incidence of BAV, and an outbred, second control line, acquired from Charles River Laboratories. Three experimental groups were fed with standard diet supplemented with 2% cholesterol plus 15% butter during five months. In parallel, three control groups were fed with unmodified standard diet. Hyperlipidic diets induced lesions in the aortic valve and ascending aortic wall, i.e. subendothelial lipid deposits, valve sclerosis, and neo-intima in the aorta. We performed a preliminary, qualitative, comparative study of the lesions associated with the different animal populations and valvular phenotypes. Our results indicate that (1) the type and severity of the lesions varied among the three hamster populations, suggesting that genetic factors may be involved; (2) the aortic valve morphology seems not to determine the severity of the valvular lesions. We conclude that our hamster strain with high incidence of BAV is a promising animal model for studies on human aortic stenosis. This work was supported by P10-CTS-6068.Universidad de Málaga. Campus de Excelencia Andalucía Tech. P10-CTS-6068

The anatomical components of the cardiac outflow tract of the bichir, polypterus senegalus. Evolutionary significance

El resumen aparece en el Program & Abstracts of the 10th International Congress of Vertebrate Morphology, Barcelona 2013.Anatomical Record, Volume 296, Special Feature — 1: P-077.In chondrichthyans and actinopterygians, the outflow tract of the heart, namely, the cardiac portion intercalated between the ventricle and the ventral aorta, consists of two anatomical components: conus arteriosus and bulbus arteriosus. In chondrichthyans and extant representatives of phylogenetically ancient actinopterygian groups, the conus and bulbus are well-developed in size, whereas in most teleosts, the bulbus is markedly larger than the conus. Current knowledge about the cardiac outflow tract of the polypteriformes is scarce and highly contradictory, a fact that contrasts with their crucial phylogenetic position at the source of the actinopterygian lineage. In fact, it remains uncertain whether they have a bulbus at the arterial pole of the heart. The present study aimed to elucidate the anatomical arrangement of the cardiac outflow tract of the bichir in an attempt to improve our understanding of the evolution of the vertebrate heart. We examined the hearts from 12 bichirs using histochemical and immunohistochemical techniques. Our findings showed that the outflow tract of the bichir consists of two components, namely, a long conus arteriosus, largely composed of myocardial tissue and furnished with a variable number of valves at its luminal side, and a very short, elastin rich bulbus arteriosus, devoid of myocardium. The bulbus has an arterial-like histological composition. However, it differs from the aorta because it has a thicker wall, shows a different arrangement of the histological elements, is covered by the epicardium and is crossed by coronary arteries. The present observations are consistent with the notion that the conus arteriosus and the bulbus arteriosus have coexisted from the beginning of the jawed vertebrate radiation. This is of particular interest, because there is evidence that the bulbus arteriosus, which is a second heart field derivative, is homologous with the intrapericardial portions of the aorta and pulmonary artery of birds and mammals.Proyecto CGL2010-16417/BOS; Fondos FEDER

The Myosin Heavy Chain specific A4.1025 antibody discriminates different cardiac segments in ancient groups of gnathostomes: Morphological and evolutionary implications

El resumen aparece en el Program & Abstracts of the 11th International Congress of Vertebrate Morphology, Washington DC 2016. Anatomical Record, Volume 299, Special Feature: 263.The pan-Myosin Heavy Chain (pan-MyHC) marker MF20 have been reported to show similar, homogeneous signal in the myocardial segments of the heart of teleosts and tetrapods. However, in an ongoing study of the myocardial structure of the dogfish (Scyliorhinus canicula; Chondrichthyes), we observed differential immunostaining of the cardiac segments using another pan-MyHC, the A4.1025 antibody. In order to investigate the relevance of this finding for better understanding of the morphology and evolution of the vertebrate heart, we performed immunohistochemistry, slot blot and western blot in several species of chondrichthyans, actinopterygians and mammals using the above mentioned antibodies. In the dogfish heart, A4.1025 and MF20 specifically recognized MyHC isoforms, although with different degree of affinity. MF20 reactivity was homogeneous and high in all the myocardial segments. However, A4.1025 reactivity was heterogeneous. It was high in the sinus venosus (external layer), atrium and atrioventricular region, low in the ventricle and conus arteriosus, and null in the internal layer of the sinus venosus. A heterogeneous pattern of A4.1025 immunoreactivity was also detected in two other elasmobranchs, a holocephalan, a polypteryform and an acipenseriform. In all of these species, MF20 immunoreactivity was homogeneous. In addition, both markers showed a homogeneous immunoreactivity pattern in teleosts and mammals. Our results indicate that in the hearts of ancient gnathostomes, in all of which a conspicuous conus arteriosus exists, one or more MyHC isoforms with low affinity for A4.1025 show segment-specific distributions. Thus, A4.1025 appears to be an appropriated marker to identify the cardiac segments and their boundaries. We propose that the segmentspecific distribution of MyHC isoforms may generate a particular type of myocardial contractility associated with the presence of a conus arteriosus.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. CGL2014-52356-P, CEIMAR, BIO 203, FEDE

Variational approach for walking solitons in birefringent fibres

We use the variational method to obtain approximate analytical expressions for the stationary pulselike solutions in birefringent fibers when differences in both phase velocities and group velocities between the two components and rapidly oscillating terms are taken into account. After checking the validity of the approximation we study how the soliton pulse shape depends on its velocity and nonlinear propagation constant. By numerically solving the propagation equation we have found that most of these stationary solutions are stable.Comment: LaTeX2e, uses graphicx package, 23 pages with 8 figure

Anatomical, histochemical and immunohistochemical characterization of the outflow tract of ray hearts (Rajiformes; Chondrichthyes)

El resumen aparece en el Program & Abstracts of the 11th International Congress of Vertebrate Morphology, Washington DC 2016. Anatomical Record, Volume 299, Special Feature: 264.Recent work has shown that the cardiac outflow tract of sharks and chimaeras does not consist of a single myocardial component, the conus arteriosus, as classically accepted, but two, namely, the myocardial conus arteriosus and the non-myocardial bulbus arteriosus. However, the anatomical composition of the outflow tract of the batoid hearts remains unknown. The present study was designed to fill this gap. The material examined consisted of hearts of two species of rays, namely, the Mediterranean starry ray (Raja asterias) and sandy ray (Leucoraja circularis). They were studied using scanning electron microscopy, and histochemical and inmunohistochemical techniques. In both species, the outflow tract consists of two components, proximal and distal with regard to the ventricle. The proximal component is the conus arteriosus; it is characterized by the presence of compact myocardium in its wall and several transverse rows of pocket-shaped valves at its luminal side. Each valve consists of a leaflet and its supporting sinus. Histologically, the leaflet has two fibrosas, inner and outer, and a middle coat, the spongiosa. The distal component lacks myocardium. Its wall consists of smooth muscle cells, elastic fibers and collagen. Thus, it shows an arterial-like structure. However, it differs from the aorta because it is covered by the epicardium and crossed by coronary arteries. These findings indicate that the distal component is morphologically equivalent to the bulbus arteriosus of sharks and chimaeras. In contrast to foregoing descriptions, the valves of the first transverse row are distally anchored to the bulbus arteriosus and not to the ventral aorta. Our findings give added support to the notion that presence of a bulbus arteriosus at the arterial pole of the heart is common to all chondrichtyans, and not an apomorphy of actinopterygians as classically thought.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. CGL2014-52356-P, CEIMAR, BIO 203, FEDE