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We have previously identified several members of the Wnt/ [beta]-catenin pathway that are differentially expressed in a mouse model with deficient coronary vessel formation. Systemic ablation of [beta]-catenin expression affects mouse development at gastrulation with failure of both mesoderm development and axis formation. To circumvent this early embryonic lethality and study the specific role of [beta]-catenin in coronary arteriogenesis, we have generated conditional [beta]-catenin-deletion mutant animals in the proepicardium by interbreeding with a Cre-expressing mouse that targets coronary progenitor cells in the proepicardium and its derivatives. Ablation of [beta]-catenin in the proepicardium results in lethality between embryonic day 15 and birth. Mutant mice display impaired coronary artery formation, whereas the venous system and microvasculature are normal. Analysis of proepicardial [beta]-catenin mutant cells in the context of an epicardial tracer mouse reveals that the formation of the proepicardium, the migration of proepicardial cells to the heart, and the formation of the primitive epicardium are unaffected. However, subsequent processes of epicardial development are dramatically impaired in epicardial-[beta]-catenin mutant mice, including failed expansion of the sub-epicardial space, blunted invasion of the myocardium, and impaired differentiation of epicardium-derived mesenchymal cells into coronary smooth muscle cells. Our data demonstrate a functional role of the epicardial [beta]-catenin pathway in coronary arteriogenesis. cardiovascular development | smooth muscle | proepicardium | Wnt signaling

El objetivo de esta investigación fue describir la interacción entre Salvia bogotensis (Lamiaceae) y las moscas de las flores (Diptera: Syrphidae) en un ambiente urbano, el jardín botánico "José Celestino Mutis" (Bogotá D.C.). Una vez comprobada la existencia del síndrome de entomofilia, se caracterizó la morfología floral, la composición taxonómica, la riqueza y la abundancia de las especies de sírfidos identificadas como visitantes florales, así como la morfometría cefálica y bucal. S. bogotensis presenta el síndrome de la entomofilia con ausencia de autofecundación. La comunidad de sírfidos asociada con esta comprende nueve especies, agrupadas en cinco géneros. Las especies son Allograpta neotropica Curran, 1936, Allograpta exotica Wiedermann, 1830, Allograpta annulipes Macquart, 1850, Allograpta aenea Hull, 1937, Lejops mexicana Macquart, 1842, Platycheirus ecuadoriensis Fluke, 1945, Platycheirus fenestrata Macquart, 1842, Syrphus shoree Fluke, 1950 y Toxomerus sp. 1. Las especies de moscas identificadas presentan en su conjunto características conductuales y morfológicas asociadas a polinizadores de baja eficiencia, con una baja tasa de visitas, incapacidad de activación de los balancines y un mínimo contacto corporal del insecto con las anteras y el estigma de la flor. Adicionalmente, las moscas presentan una carga muy baja de granos de polen de S. bogotensis sobre el cuerpo y alta inversión de tiempo en la limpieza de su cuerpo (acicalamiento). Las flores visitadas por estos insectos no dieron origen a frutos. Todo lo anterior permite concluir que dichas moscas no son polinizadores efectivos de S. bogotensis. Además de dípteros, se observaron varias especies de insectos visitantes florales de S. bogotensis pertenecientes a las familias Apidae, Halictidae y Megachilidae. Los sírfidos se benefician por el consumo de polen de S. bogotensis, pero no interfieren en el crecimiento y el desarrollo de la planta, por lo cual se infiere que la interacción entre las moscas de las flores y S. bogotensis es de tipo comensalismo.

The role of HF-1b gene from ventricular and neural crest cells lineages in the development of cardiac conduction system in vertebrate embryos is studied.

Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor [alpha] (RXR [alpha]), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and cellular mechanisms controlled by RXR [alpha] signaling in this process are unclear, because a myocardium-restricted RXR [alpha] mutation does not perturb heart morphogenesis. Here, we analyze a series of tissue-restricted mutations of the RXR [alpha] gene in the cardiac neural crest, endothelial, and epicardial lineages, and we show that RXR [alpha] signaling in the epicardium is required for proper cardiac morphogenesis. Moreover, we detect an additional phenotype of defective coronary arteriogenesis associated with RXR [alpha] deficiency and identify a retinoid-dependent Wnt signaling pathway that cooperates in epicardial epithelial-to-mesenchymal transformation. coronary vessels | epicardium | retinoids | wnt | FGF

Alcoholic cardiomyopathy (ACM) resulting from chronic alcohol misuse is one of the main contributors leading to heart failure and cardiovascular mortality. Fibroblast growth factor 21 (FGF21) is a well‐established cardioprotective factor. We aimed to study the role of FGF21 in experimentally induced models and clinical affected patients with cardiac damage due to chronic alcohol consumption. We found that circulating FGF21 levels and cardiac FGF21 and β‐klotho protein levels were increased in subjects with chronic alcohol consumption. As an experimental model of ACM, we fed wild‐type and Fgf21 knockout (Fgf21−/−) mice with a 4% alcohol liquid diet for 4 and 12 weeks. FGF21 circulating levels and FGF21 expression in the myocardium were also increased in wild‐type mice after chronic alcohol intake. Fgf21−/− mice develop a higher degree of cardiac hypertrophy, fibrosis, and cardiac dysfunction after chronic alcohol consumption than wild‐type mice. Moreover, the myocardium of Fgf21−/− mice showed signs of metabolic deregulation, oxidative stress, and mitochondrial dysfunction after alcohol intake. Finally, human cardiac biopsies from patients with chronic alcohol consumption developing ACM presented a higher degree of oxidative stress which positively correlated with the FGF21 protein levels in the myocardium. We conclude that plasma levels and cardiac myocyte FGF21 expression were induced in response to chronic alcohol consumption. The lack of FGF21 aggravated cardiac damage produced by ACM, in association with enhanced mitochondrial and oxidative stress, thus pointing to FGF21 as a protective agent against development of alcohol‐induced cardiomyopathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the risk of bronchopulmonary dysplasia. Continuous positive airway pressure (CPAP), a form of noninvasive ventilation, is commonly used in modern neonatology. Limited clinical data are available on the acute and long-term effect of neonatal exposure to CPAP on the lung. Given the restricted clinical data, newborn animal models have been used to study the influence of CPAP on lung structure and function. The findings of animal studies can guide neonatal care and improve the use of CPAP. Methods: A systematic review of electronic databases (Medline, Embase, and Cinahl) was performed using the medical subject heading terms, "CPAP" or "continuous positive airway pressure" and "animals" and "newborn." Abstracts were screened for inclusion using predetermined eligibility criteria. Results: In total, 235 abstracts were identified and screened for inclusion. Of these, 21 papers were included. Large (N = 18) and small (N = 3) animal models investigated the effects of CPAP. Pulmonary outcomes included gas exchange, lung structure and function, surfactant metabolism, lung inflammation and injury, and the effect of intrapulmonary therapy. Compared to mechanical ventilation, CPAP improves lung function, evokes less lung injury, and does not disrupt alveolar development. Surfactant administration combined with CPAP further improves respiratory outcomes. Of concern are findings that CPAP may increase airway reactivity. Discussion/Conclusion: CPAP offers numerous advantages over mechanical ventilation for the immature lung. The combination of CPAP and exogenous surfactant administration offers further pulmonary benefit. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of the Birmingham Vasculitis Activity Score (BVAS), version 3, and the Five Factor Score (FFS), version 1996 and version 2009, to assess survival in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods: A total of 550 patients with AAV (41.1% with granulomatosis with polyangiitis, 37.3% with microscopic polyangiitis, and 21.6% with eosinophilic granulomatosis with polyangiitis), diagnosed between 1990 and 2016, were analyzed. Receiver operating characteristic (ROC) curves and multivariable Cox analysis were used to assess the relationships between the outcome and the different scores.Results: Overall mortality was 33.1%. The mean ± SD BVAS at diagnosis was 17.96 ± 7.82 and was significantly higher in nonsurvivors than in survivors (mean ± SD 20.0 ± 8.14 versus 16.95 ± 7.47, respectively; P < 0.001). The mean ± SD 1996 FFS and 2009 FFS were 0.81 ± 0.94 and 1.47 ± 1.16, respectively, and were significantly higher in nonsurvivors than in survivors (mean ± SD 1996 FFS 1.17 ± 1.07 versus 0.63 ± 0.81 [P < 0.001] and 2009 FFS 2.13 ± 1.09 versus 1.15 ± 1.05 [P < 0.001], respectively). Mortality rates increased according to the different 1996 FFS and 2009 FFS categories. In multivariate analysis, BVAS, 1996 FFS, and 2009 FFS were significantly related to death (P = 0.007, P = 0.020, P < 0.001, respectively), but the stronger predictor was the 2009 FFS (hazard ratio 2.9 [95% confidence interval 2.4-3.6]). When the accuracy of BVAS, 1996 FFS, and 2009 FFS to predict survival was compared in the global cohort, ROC analysis yielded area under the curve values of 0.60, 0.65, and 0.74, respectively, indicating that 2009 FFS had the best performance. Similar results were obtained when comparing these scores in patients diagnosed before and after 2001 and when assessing the 1-year, 5-year, and long-term mortality. Correlation among BVAS and 1996 FFS was modest (r = 0.49; P < 0.001) but higher than between BVAS and the 2009 FFS (r = 0.28; P < 0.001).Conclusion: BVAS and FFS are useful to predict survival in AAV, but the 2009 FFS has the best prognostic accuracy at any point of the disease course. [ABSTRACT FROM AUTHOR]

The mammal mitochondrial adenine nucleotide translocase exhibits a six transmembrane segment model in the inner mitochondrial membrane. The hydrophilic loops M2 and M3 show matrix orientation as deduced by epitope analysis.

Abstract: Objectives: Here we address the capacity of bone marrow-derived cells (BMDCs) to trans-differentiate into mature myocytes under the physiological stimulus of exercise training. Methods: For this purpose, we have transplanted bone marrow from mice ubiquitously expressing enhanced green fluorescence protein (eGFP) into host mice that have been subjected to a prolonged program of exercise. Results: In all successful bone marrow reconstitutions (greater than 80%), we observed rare but consistent events of bone marrow-derived cardiomyocytes, the frequency of which was unchanged upon exercise training. We have further determined whether these recruited myocytes are a product of trans-differentiation or fusion by the use of a genetic system that distinguishes cell fusion from trans-differentiation in a single-cell assay. Conclusions: We concluded that both in the unchallenged mouse and in the trained specimens, fusion is the most prominent mechanism by which bone marrow-derived cells are observed in the myocyte compartment. [Copyright &y& Elsevier]

Overexpression of adenine nucleotide translocase-1 (ANT1) is known to induce apoptosis (Bauer, M. K., Schubert, A., Rocks, O., and Grimm, S. (1999) J. Cell Biol. 147, 1493-1501), but the mechanisms involved remain unclear. In this study we show that ANT1 overexpression results in a recruitment of the IkappaBalpha-NF-kappaB complex into mitochondria, with a coincident decrease in nuclear NF-kappaB DNA binding activity. In this situation, NF-kappaB transcriptionally regulated genes with antiapoptotic activity, such as Bcl-XL, MnSOD2, and c-IAP2, are down-regulated, and consequently, cells are sensitized to apoptosis. Accordingly, co-expression of p65 partially interferes with the proapoptotic effect of ANT1 overexpression. Despite the high identity of the two isoforms, overexpression of ANT2 does not exert an apoptotic effect; this lack of apoptotic activity is correlated with the absence of mitochondrial IkappaBalpha-NF-kappaB recruitment or changes in NF-kappaB activity. Thus, we propose that the mitochondrial recruitment of NF-kappaB observed following ANT1 overexpression has an important role in ANT1 proapoptotic activity.