The embryonic epicardium: an essential element of cardiac development

The epicardium has recently been identified as an active and essential element of cardiac development. Recent reports have unveiled a variety of functions performed by the embryonic epicardium, as well as the cellular and molecular mechanisms regulating them. However, despite its developmental importance, a number of unsolved issues related to embryonic epicardial biology persist. In this review, we will summarize our current knowledge about (i) the ontogeny and evolution of the epicardium, including a discussion on the evolutionary origins of the proepicardium (the epicardial primordium), (ii) the nature of epicardial–myocardial interactions during development, known to be essential for myocardial growth and maturation, and (iii) the contribution of epicardially derived cells to the vascular and connective tissue of the heart. We will finish with a note on the relationships existing between the primordia of the viscera and their coelomic epithelial lining. We would like to suggest that at least a part of the properties of the embryonic epicardium are shared by many other coelomic cell types, such that the role of epicardium in cardiac development is a particular example of a more general mechanism for the contribution of coelomic and coelomic-derived cells to the morphogenesis of organs such as the liver, kidneys, gonads or spleen.This work was supported by grants BFU2008–02384, BFU2009–07929 and SAF2008–1883, (Ministerio de Ciencia e Innovación), RD06/0010/0015 (TerCel network, ISCIII), RD96/0014/1009 (RECAVA network, ISCIII), P08-CTS-03618 (Junta de AndalucÌa) and LSHM-CT-2005–018630 (VI framework, UE)

Optimization of α-tocopherol and ascorbyl palmitate addition for the stabilization of sardine oil

The purpose of the present work was to optimize the addition of natural antioxidants (α- tocopherol and ascorbyl palmitate) for the stabilization of sardine oil rich in omega-3 PUFA. The optimal values for peroxide value (PV), which minimizes primary oxidation products, were obtained at low concentrations of α-tocopherol (50–207 ppm), high content of ascorbyl palmitate (450 ppm) and 50 ppm citric acid. On the other hand, optimal values for <em>p</em>-anisidine value (AV), which minimizes secondary oxidation products, were found at medium concentrations of α-tocopherol (478–493 ppm), high contents of ascorbyl palmitate (390–450 ppm) and 50 ppm citric acid. The conflicting effect of α-tocopherol on the individual optimization of PV and AV motivated the generation of a Pareto front (set of non inferior solutions) employing the weighted-sum multi-objective optimization technique.<br><br>El objetivo de este trabajo fue optimizar la adición de antioxidantes naturales (α-tocoferol y palmitato de ascorbilo) para la estabilización de aceite de sardina rico en omega-3 PUFA. Bajas concentraciones de α-tocoferol (50–207 ppm) combinadas con la adicción de antioxidantes secundarios como palmitato de ascorbilo (450 ppm) y ácido cítrico (50 ppm), minimizaron la formación de hidroperóxidos en el aceite de sardina estudiado. Sin embargo, los productos secundarios de oxidación se redujeron para concentraciones medias de α-tocoferol (478–493 ppm), altas de palmitato de ascorbilo (390–450 ppm) y 50 ppm de ácido cítrico. El efecto contradictorio de la concentración de α-tocoferol en la optimización individual del índice de peróxidos e índice de <em>p</em>-anisidina motivó la realización de una optimización simultánea que permite satisfacer la optimización de cada una de las variables individuales en el grado deseado

Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations

Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24-/- mouse model of HGPS. Challenge of Zmpste24-/- mice with the ß-adrenergic agonist isoproterenol did not trigger ventricular arrhythmia but caused bradycardia-related premature ventricular complexes and slow-rate polymorphic ventricular rhythms during recovery. Patch-clamping in Zmpste24-/- cardiomyocytes revealed prolonged calcium-transient duration and reduced sarcoplasmic reticulum calcium loading and release, consistent with the absence of isoproterenol-induced ventricular arrhythmia. Zmpste24-/- progeroid mice also developed severe fibrosis-unrelated bradycardia and PQ interval and QRS complex prolongation. These conduction defects were accompanied by overt mislocalization of the gap junction protein connexin43 (Cx43). Remarkably, Cx43 mislocalization was also evident in autopsied left ventricle tissue from HGPS patients, suggesting intercellular connectivity alterations at late stages of the disease. The similarities between HGPS patients and progeroid mice reported here strongly suggest that defective cardiac repolarization and cardiomyocyte connectivity are important abnormalities in the HGPS pathogenesis that increase the risk of arrhythmia and premature death.Peer ReviewedPostprint (published version

Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development.

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.The authors thank Dr. A. Rojas (CABIMER, Sevilla, Spain) and Prof. Thalia Papayannopoulou (University of Washington, WA, USA) for sharing with us the G2- Gata4-Cre and Itga4-floxed mouse lines, respectively. We also thank Vanessa Benhamo (Institut Imagine) for her expert support with HREM. Finally, we thank all members of “DeCA” laboratory (University of Málaga, Málaga, Spain), and the “Heart Morphogenesis” laboratory (Institut Imagine and Institut Pasteur, Paris, France) for their help and fruitful discussions on this paper. This work was supported by the Spanish Ministry of Science, R+D+i National Programme [grants RTI2018-095410-RBI00 and PID2021-122626-OB-I00], Spanish Ministry of Science-ISCIII [grant number RD16/0011/0030], and University of Málaga [grant number UMA18-FEDERJA-146] to [JMPP]; Consejería de Salud y Familias, Junta de Andalucía [grant number PIER-0084- 2019] to [JAGD]; University of Málaga [grant number I Plan Propio-UMA-A.4] to [ARV]; Spanish Ministry of Science, Innovation, and Universities (MCIU) (CIBER CV) [grant numbers PID2019-104776RB-I00 and CB16/11/00399] to [JLDLP].S

Science and technology parks as innovation intermediaries for green innovation

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Springer in Lecture Notes in Mechanical Engineering on 18/08/2020.Available online: https://link.springer.com/chapter/10.1007/978-3-030-48021-9_101This paper discusses how science and technology parks (STPs) act as intermediaries for projects regarding green innovation. The empirical evidence is gathered through a case study of the City of Knowledge in Panama. For the recent Panama channel’s expansion, local authorities faced the need to improve the water resource management to secure enough fresh water for the canal’s operation. We inductively analysed data from 24 interviews, documents and participant observer. Preliminary results show the intermediation of STPs in green innovation processes in three phases: a first intermediation process is the STP as a hub for knowledge generation, including training for entrepreneurship. A second stage of the park as an innovation intermediary regards to an arena for knowledge and technology transfer, including collaboration with universities. A third phase implies financing and brokerage of green innovation between local and global actors. Our results challenge the existing literature about STPs with a narrow focus on economic spillover effects, or as hubs for attracting and developing cutting-edge technological innovations.acceptedVersio

Psychometric evaluation of the nine-item problematic Internet use questionnaire (PIUQ-9) in nine European samples of internet users

Objectives: The nine-item Problematic Internet Use Questionnaire (PIUQ-9) is a brief self-report screening instrument for problematic internet use. The main objective of the present study was to explore the psychometric properties of the PIUQ-9 among nine different language-based samples of European internet users (Italian, German, French, Polish, Turkish, Hungarian, English, and Greek). Methods: The total sample comprised 5,593 internet users (38.1% men), aged between 18 and 87 years (M = 25.81; SD = 8.61). Via online recruitment, participants completed the PIUQ-9, the Brief Symptom Inventory (BSI) and items about time spent online. Results: Confirmatory factor analysis demonstrated that the bifactor model with one general factor (i.e., general problem) and two-specific factors (i.e., obsession and neglect + control disorder) yielded acceptable or good fit indices in all subsamples except for one. The common variance index in the bifactor model indicated that the general problem factor explained from 57.0 to 76.5% of common variance, which supports the presence of a strong global factor. According to the multiple indicators multiple causes (MIMIC) model, psychiatric symptoms had a moderate-to-strong direct effect on the general problem factor in all subsamples, ranging from β = 0.28 to β = 0.52 supporting the construct validity of the scale. Furthermore, in a majority of the subsamples, time spent online during the weekend had considerably higher effect sizes on the general problem factor than time spent online during weekdays. Conclusion: The present study highlights the appropriate psychometric properties of the PIUQ-9 across a number of European languages and cultures

Cardiovascular development: towards biomedical applicability: Epicardium-derived cells in cardiogenesis and cardiac regeneration

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium- derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular fibroblasts. Moreover, epicardium-derived cells are important regulators of formation of the compact myocardium, the coronary vasculature, and the Purkinje fiber network, thus being essential for proper cardiac development. The fibrous structures of the heart such as the fibrous heart skeleton and the semilunar and atrioventricular valves also depend on a contribution of these cells during development. We hypothesise that the essential properties of epicardium-derived cells can be recapitulated in adult diseased myocardium. These cells can therefore be considered as a novel source of adult stem cells useful in clinical cardiac regeneration therapy

Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin

Epicardial epithelial-mesenchymal transition (EMT) is hypothesized to generate cardiovascular progenitor cells that differentiate into various cell types, including coronary smooth muscle and endothelial cells, perivascular and cardiac interstitial fibroblasts and cardiomyocytes. Here we show that an epicardial-specific knockout of Wt1 leads to a reduction of mesenchymal progenitor cells and their derivatives. We demonstrate that Wt1 is essential for repression of the epithelial phenotype in epicardial cells and during Embryonic Stem (ES) cell differentiation, through direct transcriptional regulation of Snail (Snai1) and E-cadherin (Cdh1), two of the major mediators of EMT. Some mesodermal lineages fail to form in Wt1 null embryoid bodies but this effect is rescued by the expression of Snai1, underlining the importance of EMT in generating these differentiated cells. These new insights into the molecular mechanisms regulating cardiovascular progenitor cells and EMT will shed light on the pathogenesis of heart diseases and may help the development of cell based therapies

Review on catalytic cleavage of C-C inter-unit linkages in lignin model compounds: Towards lignin depolymerisation

Lignin depolymerisation has received considerable attention recently due to the pressing need to find sustainable alternatives to fossil fuel feedstock to produce chemicals and fuels. Two types of interunit linkages (C–C and C–O linkages) link several aromatic units in the structure of lignin. Between these two inter-unit linkages, the bond energies of C–C linkages are higher than that of C–O linkages, making them harder to break. However, for an efficient lignin depolymerisation, both types of inter-unit linkages have to be broken. This is more relevant because of the fact that many delignification processes tend to result in the formation of additional C–C inter-unit bonds. Here we review the strategies reported for the cleavage of C–C inter-unit linkages in lignin model compounds and lignin. Although a number of articles are available on the cleavage of C–O inter-unit linkages, reports on the selective cleavage of C–C inter-unit linkages are relatively less. Oxidative cleavage, hydrogenolysis, two-step redox-neutral process, microwave assisted cleavage, biocatalytic and photocatalytic methods have been reported for the breaking of C–C inter-unit linkages in lignin. Here we review all these methods in detail, focused only on the breaking of C–C linkages. The objective of this review is to motivate researchers to design new strategies to break this strong C–C inter-unit bonds to valorise lignins, technical lignins in particular