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

Is the bulbus arteriosus of fish homologous to the mamalian intrapericardial thoracic arteries?

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-089.Two major findings have significantly improved our understanding of the embryology and evolution of the arterial pole of the vertebrate heart (APVH): 1) a new embryonic presumptive cardiac tissue, named second heart field (SHF), forms the myocardium of the outflow tract, and the walls of the ascending aorta (AA) and the pulmonary trunk (PT) in mammals and birds; 2) the bulbus arteriosus (BA), previously thought to be an actinopterygian apomorphy, is present in all basal Vertebrates, and probably derives from the SHF. We hypothesized that the intrapericardial portions of the AA and the PT of mammals are homologous to the BA of basal vertebrates. To test this, we performed 1) a literature review of the anatomy and embryology of the APVH; 2) novel anatomical, histomorphological, and embryological analyses of the APVH, comparing basal (Galeus atlanticus), with apical (Mus musculus and Mesocricetus auratus) vertrebrates. Evidence obtained: 1) Anatomically, BA, AA, and PT are muscular tubes into the pericardial cavity, which connect the distal myocardial outflow tracts with the aortic arch system. Coronary arteries run through or originate at these anatomical structures; 2) Histologically, BA, AA, and PT show an inner layer of endothelium covered by circumferentially oriented smooth muscle cells, collagen fibers, and lamellar elastin. The histomorphological differences between the BA and the ventral aorta parallel those between intrapericardial and extrapericardial great arteries; 3) Embryologically, BA, AA, and PT are composed of smooth muscle cells derived from the SHF. They show a similar mechanism of development: incorporation of SHF‐derived cells into the pericardial cavity, and distal‐to‐proximal differentiation into an elastogenic cell linage. In conclusion, anatomical, histological and embryological evidence supports the hypothesis that SHF is a developmental unit responsible for the formation of the APVH. The BA and the intrapericardial portions of the great arteries must be considered homologous structures.Proyecto P10-CTS-6068 (Junta de Andalucía); proyecto CGL-16417 (Ministerio de Ciencia e Innovación); Fondos FEDER

Bozepinib: A Promising Selective Derivative Targeting Breast Cancer Stem Cells

Bozepinib is a potent antitumour compound that shows an IC50 of 0.166 μM against MDA-MB-231 human breast cancer cell line. It is also a very selective drug that presents a therapeutic index (TI) of 11.0 against MDA-MB-231 in relation to the normal MCF-10A. It is important to identify new cancer stem-like cells (CSCs) anticancer drugs to struggle against the resistance and the high risk of relapse in patients. In the present chapter, we show how bozepinib demonstrated selectivity on cancer cells and showed an inhibitory effect over kinases involved in carcinogenesis, proliferation and angiogenesis. Bozepinib inhibits HER-2 signaling pathway and JNK and ERK kinases. In addition, it has an inhibitory effect on AKT and VEGF together with anti-angiogenic and anti-migratory activities. Interestingly, bozepinib suppresses the formation of both mammo- and colonospheres and eliminated ALDH+ CSC subpopulations at a low micromolar range similar to salinomycin. It also induces the downregulation of SOX2, c-MYC and β-CATENIN and upregulation of the GLI-3 Hedgehog signaling repressor. Finally, bozepinib shows in vivo antitumor and anti-metastatic efficacy in xenotransplanted nude mice without presenting subacute toxicity. However, further studies in cancer patients are needed to confirm the therapeutic potential of bozepinib

Synthesis and complementary self-association of novel lipophilic π-conjugated nucleoside oligomers

The following article appeared in Organic and Biomolecular Chemistry 13.15 (2015): 4506-4513 and may be found at http://dx.doi.org/10.1039/c5ob00098j, reproduced by permission of The Royal Society of ChemistryA series of lipophilic nucleosides comprising natural and non-natural bases that are π-conjugated to a short oligophenylene-ethynylene fragment has been synthesized. These bases comprise guanosine, isoguanosine, and 2-aminoadenosine as purine heterocycles, and cytidine, isocytosine and uridine as complementary pyrimidine bases. The hydrogen-bonding dimerization and association processes between complementary bases were also studied by 1H NMR and absorption spectroscopy in order to obtain the relevant association constantsFunding from the European Research Council (ERC-StG 279548) and MINECO (CTQ2011-23659) is gratefully acknowledge

Requirement of Plasminogen Binding to Its Cell-Surface Receptor α-Enolase for Efficient Regeneration of Normal and Dystrophic Skeletal Muscle

Adult regenerative myogenesis is central for restoring normal tissue structure and function after muscle damage. In muscle repair after injury, as in severe myopathies, damaged and necrotic fibers are removed by infiltrating inflammatory cells and then replaced by muscle stem cells or satellite cells, which will fuse to form new myofibers. Extracellular proteolysis mediated by uPA-generated plasmin plays a critical role in controlling inflammation and satellite-cell-dependent myogenesis. alpha-enolase has been described as plasminogen receptor in several cell types, where it acts concentrating plasmin proteolytic activity on the cell surface. In this study, we investigated whether alpha-enolase plasminogen receptor plays a regulatory role during the muscular repair process. Inhibitors of alpha-enolase/plasminogen binding: MAb11G1 (a monoclonal antibody against alpha-enolase) and e-aminocaproic acid, EACA (a lysine analogue) inhibited the myogenic abilities of satellite cells-derived myoblasts. Furthermore, knockdown of alpha-enolase decreased myogenic fusion of myoblasts. Injured wild-type mice and dystrophic mdx mice were also treated with MAb11G1 and EACA. These treatments had negative impacts on muscle repair impairing satellite cell functions in vitro in agreement with blunted growth of new myofibers in vivo. Furthermore, both MAb11G1 and EACA treatments impaired adequate inflammatory cell infiltration and promoted extracellular matrix deposition in vivo, which resulted in persistent degeneration. These results demonstrate the novel requirement of alpha-enolase for restoring homeostasis of injured muscle tissue, by controlling the pericellular localization of plasmin activity

Informe de seguimiento de la actividad de los Ministerios en relación con los Programas del Marco General para la Mejora de la Calidad de la Administración General del Estado durante 2011: Real Decreto 951/2005, de 29 de julio, por el que se establece el Marco General para la Mejora de la Calidad en la AGE

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El papel del voluntariado universitario en la creación de una comunidad de aprendizaje.

La comunicación que presentamos describe el proceso de participación del voluntariado universitario en la comunidad de aprendizaje CEIP Albolafia de Córdoba. Dado que el papel del voluntariado en este tipo de experiencias es clave para la puesta en práctica de las actuaciones transformadoras, nuestra tarea ha estado centrada en articular la presencia de un grupo de alumnos y alumnas en el centro educativo. Por ello consideramos de interés valorar sus conocimientos previos sobre el tema, sus deseos de transformación social y sus motivaciones para participar en este proyecto. La información obtenida ha permitido reformular las actuaciones en relación a la formación, el compromiso y la participación en la comunidad de aprendizaje

Land-use change and windstorms legacies drove the recolonization dynamics of laurel forests in Tenerife, Canary islands

Laurel forests are quite relevant for biodiversity conservation and are among the island ecosystems most severely damaged by human activities. In the past, Canary laurel forests have been greatly altered by logging, livestock and agriculture. The remains of laurel forests are currently protected in the Canary Islands (Spain). However, we miss basic information needed for their restoration and adaptive management, such as tree longevity, growth potential and responsiveness to natural and anthropogenic disturbances. Using dendrochronological methods, we studied how forest dynamic is related to land-use change and windstorms in two well-preserved laurel forests on Tenerife Island. Wood cores were collected from over 80 trees per stand at three stands per forest. We used ring-width series to estimate tree ages and calculate annual basal area increments (BAI), cumulative diameter increases, and changes indicative of released and suppressed growth. Twelve tree species were found in all stands, with Laurus novocanariensis, Ilex canariensis and Morella faya being the most common species. Although some individuals were over 100 years old, 61.8%–88.9% of the trees per stand established between 1940 and 1970, coinciding with a post-war period of land abandonment, rural exodus and the onset of a tourism economy. Some trees have shown growth rates larger than 1 ​cm diameter per year and most species have had increasing BAI trends over the past decades. Strong growth releases occurred after windstorms at both sites, but the effects of windstorms were site-dependent, with the 1958 storm affecting mainly the eastern tip of the island (Anaga massif) and the 1991 storm the western tip (Teno massif). Given the great ability of laurel forest trees to establish after land use cessation and to increase growth after local disturbances such as windstorms, passive restoration may be sufficient to regenerate this habitat in currently degraded areas.12 página

La enfermedad crónica infantil. Repercusiones emocionales en el paciente y en la familia.

La OMS define la salud como el estado de completo bienestar físico, mental y social. De este modo, se pasa de entender la salud únicamente como un concepto biológico, para entenderla como una dimensión biopsicosocial (Rubio et al., 2010). En general, la enfermedad, sobre todo cuando es crónica, altera en gran medida tanto la vida del paciente, como la de todas las personas de su entorno, y hace necesaria una adaptación a la situación de todas las partes implicadas (particularmente el niño y la familia). En el siguiente trabajo se pretenden analizar las distintas estrategias de afrontamiento emocional que, según la bibliografía relevante en este tema, tanto el paciente pediátrico como su círculo social más importante adoptan ante la nueva situación.Investigación realizada gracias al Proyecto I+D con ref.: EDU2009-11950 del Ministerio de Ciencia e Innovación.peerReviewe

α-Enolase, a Multifunctional Protein: Its Role on Pathophysiological Situations

α-Enolase is a key glycolytic enzyme in the cytoplasm of prokaryotic and eukaryotic cells and is considered a multifunctional protein. α-enolase is expressed on the surface of several cell types, where it acts as a plasminogen receptor, concentrating proteolytic plasmin activity on the cell surface. In addition to glycolytic enzyme and plasminogen receptor functions, α-Enolase appears to have other cellular functions and subcellular localizations that are distinct from its well-established function in glycolysis. Furthermore, differential expression of α-enolase has been related to several pathologies, such as cancer, Alzheimer’s disease, and rheumatoid arthritis, among others. We have identified α-enolase as a plasminogen receptor in several cell types. In particular, we have analyzed its role in myogenesis, as an example of extracellular remodelling process. We have shown that α-enolase is expressed on the cell surface of differentiating myocytes, and that inhibitors of α-enolase/plasminogen binding block myogenic fusion in vitro and skeletal muscle regeneration in mice. α-Enolase could be considered as a marker of pathological stress in a high number of diseases, performing several of its multiple functions, mainly as plasminogen receptor. This paper is focused on the multiple roles of the α-enolase/plasminogen axis, related to several pathologies