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

Different laboratory mouse strains show distinct coronary artery patterns

Different laboratory mouse strains show distinct coronary artery patterns. MC Fernández 1,2, A López-García 1,2, M Lorenzale 1, V Sans-Coma 1,2, 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. The C57BL/6 (BL/6) mouse strain is one of the most common models in research involving laboratory animals, particularly on studies of the cardiovascular system. It has been reported (Fernandez B, et al. J Anat 2008 212(1):12–18) that this strain presents an unusual coronary artery (CA) pattern, including congenital CA anomalies, which are clinically relevant in humans. The aim of the present study was to elucidate whether this pattern is strain-specific or appears in other mouse populations. We used stereomicroscopy, scanning electron microscopy, light microscopy, and a corrosion cast technique in 597 adult mice belonging to three inbred strains (BL/6, Balb/c, DBA/2), three outbred stocks (CD1, OF1, NMR1), two hybrid lines (129sv x BL/6, CD2F1) and wild mice. Lock-like ostium was only detected in BL/6 mice, whereas left septal artery, accessory ostium, high take-off, intramural course, and solitary ostium of one CA in aorta were present in different laboratory strains and in wild mice. However, each mouse population showed a specific incidence of these coronary conditions. These results should be taken into account when studying the murine coronary system, especially in CA occlusion experiments and in studies on cardiovascular development involving murine mutant lines. In addition, we propose that several laboratory mouse strains may serve as appropriate animal models to study several clinically relevant human congenital anomalies of the CAs. Our results suggest that some of these CA anomalies are subject to a simple mode of inheritance. This work was supported by P10-CTS-6068 and PI- 0888-2012.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. P10-CTS-6068. PI-0888-201

Efficient symbolic computation of approximated small-signal characteristics of analog integrated circuits

A symbolic analysis tool is presented that generates simplified symbolic expressions for the small-signal characteristics of large analog integrated circuits. The expressions are approximated while they are computed, so that only those terms are generated which remain in the final expression. This principle causes drastic savings in CPU time and memory, compared with previous symbolic analysis tools. In this way, the maximum size of circuits that can be analyzed, is largely increased. By taking into account a range for the value of a circuit parameter rather than one single number, the generated expressions are also more generally valid. Mismatch handling is explicitly taken into account in the algorithm. The capabilities of the new tool are illustrated with several experimental result

A Family of matroid intersection algorithms for the computation of approximated symbolic network functions

In recent years, the technique of simplification during generation has turned out to be very promising for the efficient computation of approximate symbolic network functions for large transistor circuits. In this paper it is shown how symbolic network functions can be simplified during their generation with any well-known symbolic network analysis method. The underlying algorithm for the different techniques is always a matroid intersection algorithm. It is shown that the most efficient technique is the two-graph method. An implementation of the simplification during generation technique with the two-graph method illustrates its benefits for the symbolic analysis of large analog circuits

Algorithm for efficient symbolic analysis of large analogue circuits

An algorithm is presented that generates simplified symbolic expressions for the small-signal characteristics of large analogue circuits. The expressions are approximated while they are computed, so that only the most significant terms are generated which remain in the final expression. This principle leads to dramatic savings in CPU time and memory compared to existing techniques, significantly increasing the maximum size of circuits that can be analysed. By taking into account a range for the value of a circuit parameter rather than one single number the generated symbolic expressions are also generally valid

Symbolic analysis of large analog integrated circuits by approximation during expression generation

A novel algorithm is presented that generates approximate symbolic expressions for small-signal characteristics of large analog integrated circuits. The method is based upon the approximation of an expression while it is being computed. The CPU time and memory requirements are reduced drastically with regard to previous approaches, as only those terms are calculated which will remain in the final expression. As a consequence, the maximum circuit size amenable to symbolic analysis has largely increased. The simplification procedure explicitly takes into account variation ranges of the symbolic parameters to avoid inaccuracies of conventional approaches which use a single value. The new approach is also able to take into account mismatches between the symbolic parameters

Ultraestructura y desarrollo de la pared celular del grano de polen del olivo (Olea europaea): II. Zona apertural

En el estadía de joven microspora, la zona de las tres aperturas de l grano de Ol ea europaea presenta una diferenciación de la endexina en forma de lente biconvexa, con estructuras lame lares en su interior . La zona basal de la exina va disminuyendo hasta desaparecer en la región de l as aperturas, al mismo tiempo que lo hace l a parte escul t urada, que también se hace mínima en la zona central de la apertura . Durante la vacuolación de la microspora se i nicia la formación de la intina, que en las aperturas adquiere forma de bolsa o casquete cargada de túbulos, formados de evaginaciones del plasmal ema . El número de estos túbulos aumenta considerablemente a lo largo de la formación del grano bice l ul ar siendo siempre su contenido poco denso. La lente biconvexa de la endexina desaparece com9, tal , al producirse un aumento de volumen del grano y como consecuencia de una mayor extensión de la región apertura!. En la parte externa y central de la apertura se observa materi al fibrilar denso a los electrones. En el pqlen maduro los túbulos de l a intina apertura! de jan de estar en contacto con e l plasmalema, siendo su contenido cada vez más denso a los electrones. Previa a la dehiscencia de la antera, la zona apertura! est á muy abultada, desapareciendo en el ápice cualquier componente de la exi na. Se discu ten nuestros resultados en relaci ón con los de otros autoresIn t he stage of the young microspore of Olea eur opaea, the endexine presents a differentiation in the zone of the three apertures which is lens- shaped in form, with lamellated structure with i n. The basal zone of the ex ine becomes thinner until i t di sappears, and similarly t he sculptured part al so becomes minimal in the central zone of the aperture . During microspore vacuolation t he fo r mation of intine starts. In the apertur es the i nti ne takes the form of a bag 1 l oaded wi th tubul es 1 which are m a de out o f plasmal ema evaginations. The number of these tubules increases during the formation of the bicellular pollen grain whose contents are a l ways non dense . The biconvex l ens on the endexine disappears as such be cause of the increase in grain size and as a consequence of t he extension in the area of t he aperture . At the outer surface of the pollen apertures fi brillar el ectron dense material can be observed. In the mature grain the tubules of the apertura! intine lose contact wi th the plasmal enma and t heir contents be come dense to electrons. Prior to the dehiscence of the anther, thP. zone of the apertures is very bul ky and no component of the exine is present in t he aperture apex. Our resul ts are discussed i n relation to those or other author s

Ultraestructura y desarrollo de la pared celular del grano de polen del olivo (Olea europaea): I. Zona interapertural

Se hace un estudio ultraestructural de la pared del grano de polen del olivo (Olea europaea), relacionando su desa rrol l o can la evolución de l grano , desde el estado de microspora j oven hasta l a dehiscencia de l a a ntera . Cuando la microspora se encuentra libre en el 16cul o de la antera ya es tá totalmente definida la exi na . Durante la vacuolación de la microspora se consol ida la exina estructurada por un aporte de e sporopolenina . En este tiempo también se i nicia la deposición de la i ntina. Durante la f ormación del gr ano bicelular se deposita entre l as arcadas de l a exina, una cubierta externa de materi al fi brilar densa a los electrones , procedente del t a pe tum, y presum i blemente de naturaleza proteica . Finalmente, c uando la a ntera ya está preparada para l a deh i scencia, se comple t a l a pared del g r ano con un mater ial de apar i encia l ipídica. La presencia de est e material e n el lócul o de la antera coincide con la degeneración del tapetum.The sequen ti al development of the wall of t he pollen gr ain of the olive (Olea europaea) from young microspore stage t o anther dechiscence i s descri bed. When the microspore i s released from t he tetrad and t he cal lase spec i al wall is degr aded , the exine is clearly establ ished. At t he time of vacuolation of the microspore cytoplasm the exine structur e i s consol idated wi th new sporopollenin from t he tapetum and this coi ncider wi t h t he o nset of intine development . Dur i ng t he formation of the bicel l ular g r ain, a fibril lar e l ectron dense coating material i s found i n t he i nterbacul at" s pac es . This coating probably has a protein nature produced f r om tapetum . Final l y , when the anther is r eady for deh iscence , t he pollen grain wal l is completed wi th a weak grey- stained dense mass which i s pro bably lipoida l in nature , located between t he exi ne arcade . The appear a nce ol these l i p idic globul es coinc ides •Ni th t he degeneration of tapetum ce l l

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