A developmental model for the pathogenenesis of cardiac arterio-ventricular fistulae

Coronary Artery Fistulae (CAF) are congenital coronary artery (CA) anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or a large cardiac vessel. Although their incidence in the Western population is low, CAF can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and cardiac failure. CAFs can appear as an isolated anomaly or linked to some other forms of congenital heart disease like Left Ventricular Non-Compaction (LVNC) and intrinsic CA anatomy anomalies, but their etiology remains unknown. In this work we have used two different experimental models (transgenic mice and avian embryos) to investigate on the developmental mechanics of CAF formation. In order to tackle this goal, we have manipulated epicardial development and ventricular wall compaction, two inextricably related developmental events during coronary embryogenesis. Conditional integrin α4 gene deletion in the septum transversum/proepicardial (ST/PE) region (G2-Gata4+) disrupts early epicardium development and reduces cardiomyocyte proliferation, leading to the thinning of the ventricular compact myocardial layer. Reduction in compact myocardium thickness associates to the presence of multiple ventricular myocardial discontinuities and focal endocardial extrusion. This same phenotype can be experimentally reproduced in chick embryos using a cryocauterization method (Palmquist-Gomes et al., 2016). Our results suggest that the partial absence of epicardium in α4integrin;G2-Gata4Cre mouse embryos and the cryoinjury in avian embryos generate myocardial discontinuities in the embryonic ventricular wall, which promote endocardial extrusion towards the pericardial cavity and the early contact of the endocardium with coronary progenitors at the epicardial surface of the heart. In the case of avian embryos, this phenomenon leads to precocious smooth muscle differentiation from epicardial mesenchymal cells, and the formation of pouch-like structures that closely resemble CAF. We conclude that anomalous compact myocardial embryonic growth can originate CAF.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A developmental model for the pathogenenesis of cardiac arterio-ventricular fistulae

Coronary Artery Fistulae (CAF) are congenital coronary artery (CA) anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or a large cardiac vessel. Although their incidence in the Western population is low, CAF can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and cardiac failure. CAFs can appear as an isolated anomaly or linked to some other forms of congenital heart disease like Left Ventricular Non-Compaction (LVNC) and intrinsic CA anatomy anomalies, but their etiology remains unknown. In this work we have used two different experimental models (transgenic mice and avian embryos) to investigate on the developmental mechanics of CAF formation. In order to tackle this goal, we have manipulated epicardial development and ventricular wall compaction, two inextricably related developmental events during coronary embryogenesis. Conditional integrin α4 gene deletion in the septum transversum/proepicardial (ST/PE) region (G2-Gata4+) disrupts early epicardium development and reduces cardiomyocyte proliferation, leading to the thinning of the ventricular compact myocardial layer. Reduction in compact myocardium thickness associates to the presence of multiple ventricular myocardial discontinuities and focal endocardial extrusion. This same phenotype can be experimentally reproduced in chick embryos using a cryocauterization method (Palmquist-Gomes et al., 2016). Our results suggest that the partial absence of epicardium in α4integrin;G2-Gata4Cre mouse embryos and the cryoinjury in avian embryos generate myocardial discontinuities in the embryonic ventricular wall, which promote endocardial extrusion towards the pericardial cavity and the early contact of the endocardium with coronary progenitors at the epicardial surface of the heart. In the case of avian embryos, this phenomenon leads to precocious smooth muscle differentiation from epicardial mesenchymal cells, and the formation of pouch-like structures that closely resemble CAF. We conclude that anomalous compact myocardial embryonic growth can originate CAF.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Anthropometric measures as predictive indicators of metabolic risk in a population of “holy week costaleros”

Preventive measures are a priority in those groups that perform intense physical efforts without physical preparation and that can also be overweight or obese. One of the groups that reflect these characteristics is the costaleros of the Holy Week of Andalusia, Spain. This paper aims to describe the effect of obesity on blood pressure. A descriptive cross-sectional study was conducted on 101 costaleros. The anthropometric measures were determined through segmental impedance. Cardiac recovery and anaerobic power were measured through the Ruffier–Dickson test and the Abalakov test, respectively. Blood pressure was measured when the individuals were at rest. The Kruskal–Wallis test was applied for of continuous parameters and the X2 test for dichotomous measures. Binary logistic regression models were used for the subsequent analysis with R-square and Receiver Operating Characteristic (ROC) curves. The average population was 28 years of age, 173.7 cm tall, and 82.59 Kg weigh. The excess of body fat was 11.27 Kg and Body Mass Index was 27.33 Kg/m2. 72.3% showed abnormal blood pressure and 68.2% were overweight. 32.7% had a waist-hip ratio higher than 0.94. The probability of presenting abnormal blood pressure was higher among the subjects whose fat content was higher and muscle content was lower

Thermally assisted hydrolysis and alkylation of lignins in the presence of tetra-alkylammonium hydroxides

Three different milled lignins isolated from bamboo, pine and beech, corresponding to the three different structural groups, have been subjected to pyrolysis in the presence of tetramethylammonium hydroxide (TMAH) and tetrabutylammonium hydroxide (TBAH). Pyrolysis of the lignins in the presence of TMAH releases the methyl esters and methyl ethers of the different lignin monomers. Several moieties bearing carboxylic acid groups, not previously detected using pyrolytic techniques, could be released from the three lignins, suggesting that the presence of these moieties in the lignin structure have been underestimated.The authors wish to thank the CICyT (Spanish Direction General de Investigation Cientifica y Tecnica; Project PB91-0074) for financial support.Peer Reviewe

Characterization of humic acids from low-rank coals by 13C-NMR and pyrolysis-methylation. Formation of benzenecarboxylic acid moieties during the coalification process

Instituto de Recursos Naturales y Agrobiologia de Sevilla, C.S.I.C., P.O. Box 1052, 41080-Seville, Spain; E-mail address: [email protected] acid (HA) fractions isolated from a peat and lignite deposit were studied by CP/MAS 13C-NMR and pyrolysis-methylation. Loss of carbohydrates, removal of methoxyls and formation of catechols during the coalification process was evident. Pyrolysis-methylation released a great variety of components, the lignin-derived monomers being the most prominent. A very striking feature was the release of benzenecarboxylic moieties after pyrolysis-methylation which have not been observed previously by pyrolytic techniques. These moieties were released in higher amounts from the lignite HA, suggesting that the content in carboxylic groups increase with coalification, at least up to the lignite stage. Oxidation of the C-3 side chain of the lignin structure would produce these benzenecarboxylic acids and benzylic ketones.We wish to thank the Comision Interministerial de Ciencia y Tecnologia (CICyT) for providing financial support (Project PB91-0074) and Professor H.-D. Lüdemann for recording NMR spectra.Peer reviewe

Cloning, tissue expression pattern and daily rhythms of Period1, Period2, and Clock transcripts in the XatWsh Senegalese sole, Solea senegalensis

An extensive network of endogenous oscillators governs vertebrate circadian rhythmicity. At the molecular level, they are composed of a set of clock genes that participate in transcriptional–translational feedback loops to control their own expression and that of downstream output genes. These clocks are synchronized with the environment, although entrainment by external periodic cues remains little explored in Wsh. In this work, partial cDNA sequences of clock genes representing both positive (Clock) and negative (Period1, Period2) elements of the molecular feedback loops were obtained from the nocturnal XatWsh Senegalese sole, a relevant species for aquaculture and chronobiology. All of the above genes exhibited high identities with their respective teleost clock genes, and Per– Arnt–Sim or basic helix–loop–helix binding domains were recognized in their primary structure. They showed a widespread distribution through the animal body and some of them displayed daily mRNA rhythms in central (retina, optic tectum, diencephalon, and cerebellum) and peripheral (liver) tissues. These rhythms were most robust in retina and liver, exhibiting marked Period1 and Clock daily oscillations in transcript levels as revealed by ANOVA and cosinor analysis. Interestingly, expression proWles were inverted in retina and optic tectum compared to liver. Such diVerences suggest the existence of tissue-dependent zeitgebers for clock gene expression in this species (i.e., light for retina and optic tectum and feeding time for liver). This study provides novel insight into the location of the molecular clocks (central vs. peripheral) and their diVerent phasing and synchronization pathways, which contributes to better understand the teleost circadian systems and its plasticity

Caring behaviours demonstrated to nursing students in the interpersonal relation with the faculty: A cross sectional study

Background: Nursing students need to experience caring in their educational environment in order to learn how to care for the patients. Objective: The present study describes the caring model demonstrated by the faculty to the nursing students through their behaviours, from the perspective of both students and faculty members. Design: A cross-sectional, descriptive, observational study was conducted. Participants: The sample included 286 students and faculty members. Methods: The Nursing Students’ Perceptions of Instructor Caring assessing tool was used to gather the data. Results: After analysing 676 questionnaires, it was revealed a moderately high level of caring perceived by the students. The most appreciated dimension was control versus flexibility, reporting a mean value of 82.29 and a confidence interval from 81.14 to 83.44, and the least valued was appreciation of life’s meanings, reporting a mean value of 63.90 and a confidence interval from 62.20 to 65.60. The students’ perception of the care demonstrated by the faculty was significantly lower than the care that the latter believed to transmit in all dimensions (p < 0.001). Conclusions: The caring perceived by the student was expressed through behaviours that inspired confidence in them, promoted a climate of learning and support, helped them to recognise the meaning of life, showed them flexibility and fostered their professional autonomy. The findings of this study can help to improve nursing education by providing a view of the interpersonal relations that the students established during their training with the faculty.info:eu-repo/semantics/publishedVersio

Evaluation of the accuracy of GHI and DNI forecasts by IFS and Harmonie models over Spain

Póster elaborado para la conferencia "SolarPaces 2016" celebrada los días 11-14 de octubre de 2016 en Abu Dhabi.This Project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 654984

Miro-1 links mitochondria and microtubule dynein motors to control lymphocyte migration and polarity

The recruitment of leukocytes to sites of inflammation is crucial for a functional immune response. In the present work, we explored the role of mitochondria in lymphocyte adhesion, polarity, and migration. We show that during adhesion to the activated endothelium under physiological flow conditions, lymphocyte mitochondria redistribute to the adhesion zone together with the microtubule-organizing center (MTOC) in an integrin-dependent manner. Mitochondrial redistribution and efficient lymphocyte adhesion to the endothelium require the function of Miro-1, an adaptor molecule that couples mitochondria to microtubules. Our data demonstrate that Miro-1 associates with the dynein complex. Moreover, mitochondria accumulate around the MTOC in response to the chemokine CXCL12/SDF-1α this redistribution is regulated by Miro-1. CXCL12-dependent cell polarization and migration are reduced in Miro-1-silenced cells, due to impaired myosin II activation at the cell uropod and diminished actin polymerization. These data point to a key role of Miro-1 in the control of lymphocyte adhesion and migration through the regulation of mitochondrial redistribution.This study was supported by SAF2011-25834 from the Spanish Ministry of Science and Innovation, INDISNET-S2011/BMD-2332 from the Comunidad de Madrid, Red Cardiovascular RD 12-0042-0056 from Instituto Salud Carlos III (ISCIII), and ERC-2011-AdG 294340- GENTRIS. J.M.G.-G. received salary support from the Miguel Servet (CP11/00145) ISCIII program. R.V.-B. was supported by a Juan de la Cierva postdoctoral contract from the Spanish Ministry of Economy and Competiveness (JCI-2011-09663

Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung

Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8+ T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy