Beta2-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation

Autophagy is a physiological degradative process key to cell survival during nutrient deprivation, cell differentiation and development. It plays a major role in the turnover of damaged macromolecules and organelles, and it has been involved in the pathogenesis of different cardiovascular diseases. Activation of the adrenergic system is commonly associated with cardiac fibrosis and remodeling, and cardiac fibroblasts are key players in these processes. Whether adrenergic stimulation modulates cardiac fibroblast autophagy remains unexplored. In the present study, we aimed at this question and evaluated the effects of b₂-adrenergic stimulation upon autophagy. Cultured adult rat cardiac fibroblasts were treated with agonists or antagonists of beta-adrenergic receptors (b-AR), and autophagy was assessed by electron microscopy, GFP-LC3 subcellular distribution, and immunowesternblot of endogenous LC3. The predominant expression of b₂-ARs was determined and characterized by radioligand binding assays using [³H]dihydroalprenolol. Both, isoproterenol and norepinephrine (non-selective b-AR agonists), as well as salbutamol (selective b₂-AR agonist) increased autophagic flux, and these effects were blocked by propanolol (b-AR antagonist), ICI-118,551 (selective b₂-AR antagonist), 3-methyladenine but not by atenolol (selective b₁-AR antagonist). The increase in autophagy was correlated with an enhanced degradation of collagen, and this effect was abrogated by the inhibition of autophagic flux. Overall, our data suggest that b₂-adrenergic stimulation triggers autophagy in cardiac fibroblasts, and that this response could contribute to reduce the deleterious effects of high adrenergic stimulation upon cardiac fibrosis.     

Influence of electron transport proteins on the reactions catalyzed by Fusarium fujikuroi gibberellin monooxygenases

The multifunctional cytochrome P450 monooxygenases P450-1 and P450-2 from Fusarium fujikuroi catalyze the formation of GA14 and GA4, respectively, in the gibberellin (GA)-biosynthetic pathway. However, the activity of these enzymes is qualitatively and quantitatively different in mutants lacking the NADPH:cytochrome P450 oxidoreductase (CPR) compared to CPR-containing strains. 3beta-Hydroxylation, a major P450-1 activity in wild-type strains, was strongly decreased in the mutants relative to oxidation at C-6 and C-7, while synthesis of C19-GAs as a result of oxidative cleavage of C-20 by P450-2 was almost absent whereas the C-20 alcohol, aldehyde and carboxylic acid derivatives accumulated. Interaction of the monooxygenases with alternative electron transport proteins could account for these different product distributions. In the absence of CPR, P450-1 activities were NADH-dependent, and stimulated by cytochrome b5 or by added FAD. These properties as well as the decreased efficiency of P450-1 and P450-2 in the mutants are consistent with the participation of cytochrome b5:NADH cytochrome b5 reductase as redox partner of the gibberellin monooxygenases in the absence of CPR. We provide evidence, from either incubations of GA12 (C-20 methyl) with cultures of the mutant suspended in [18O]H2O or maintained under an atmosphere of [18O]O2:N2 (20:80), that GA15 (C-20 alcohol) and GA24 (C-20 aldehyde) are formed directly from dioxygen and not from hydrolysis of covalently enzyme-bound intermediates. Thus these partially oxidized GAs correspond to intermediates of the sequential oxidation of C-20 catalyzed by P450-2.     

The embryonic phase and its implication in the hatchling size and condition of Atlantic bobtail squid <Emphasis Type="Italic">Sepiola atlantica</Emphasis>

Early life stages of cephalopods are somewhat complex due to the life history strategy or species specificity of generalized ontogenetic patterns and processes. This work aimed to determine the time length of embryonic development at different temperatures, and if the egg size is a determinant of hatchling size in Sepiola atlantica d′Orbigny, 1839–1842. Successful hatching occurred in 98.5–100% of the eggs for each female. As seen in other coleoid cephalopods, temperature determines the amount of time for embryonic development in S. atlantica, and the obtained data were very similar to other coleoid cephalopods. Developmental times for temperatures at 13 ± 0.4°C, 18 ± 0.3°C and 16.4 ± 1.1°C were 61.8 ± 3.8, 22.6 ± 1.7 and 40.1 ± 4.8 days. The duration of embryonic development and hatchling mantle length was not strictly related. The egg volume was positively related to hatchling mantle length. Our results provide new records on the duration of embryogenesis and other information on reproductive patterns in this species. Some hatching and post-hatching behaviour are shown and discussed.     

Spawning strategy in Atlantic bobtail squid <Emphasis Type="Italic">Sepiola atlantica</Emphasis> (Cephalopoda: Sepiolidae)

This study aimed to determine the spawning strategy in the Atlantic bobtail squid Sepiola atlantica, in order to add new information to the knowledge of its reproductive strategy. A total of 12 females that spawned in aquaria were examined. Characteristics of the reproductive traits and egg clutches were similar to those of other known Sepiolidae. Clutch size varied from 31 up to 115 eggs. Females of this species had incorporated up to 1.58 times of their body weight into laid eggs. The size of laid eggs showed a positive correlation with maternal body size, supporting the idea that female size is a determinant of egg size. Our data suggest that S. atlantica is an intermittent terminal spawner, and that its spawning strategy comprises group-synchronous ovary maturation, multiple egg laying, and deposition of egg clutches in different locations. The obtained data provide insights for future comparative studies on reproductive allocation.     

Cardiomyocyte death: mechanisms and translational implications

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications.     

Effects of macroalgal identity on epifaunal assemblages: native species versus the invasive species Sargassum muticum

Seaweeds are a refuge from stressful conditions associated with life on rocky intertidal shores, and there is evidence that different macrophytes support different assemblages of mobile epifauna. Introduction of non-indigenous macroalgae may have a great impact on associated epifaunal assemblages and ecosystem processes in coastal areas. Previous studies have reported conflicting evidences for the ability of epifauna to colonize non-indigenous species. Here, we analyzed epifaunal assemblages associated with three species of macroalgae that are very abundant on intertidal shores along the Galician coast: the two native species Bifurcaria bifurcata and Saccorhiza polyschides and the invasive species Sargassum muticum. We collected samples of each species from three different sites at three different times to test whether variability of epifaunal assemblages was consistent over space and time. Epifaunal assemblages differed between the three macroalgae. Results suggested that stability and morphology of habitat played an important role in shaping the structure of epifaunal assemblages. This study also showed that the invasive S. muticum offered a suitable habitat for many invertebrates.     

Chronology of Deep Nodes in the Neotropical Primate Phylogeny: Insights from Mitochondrial Genomes

The evolution of Neotropical Primates (NP) is permeated by factors associated with the pattern of diversification and the biogeography of the major lineages. These questions can be better understood by providing a robust estimate of the chronological scenario of NP evolution, a reason why molecular dating methods have been widely applied. One aspect of especial interest is the timing of diversification of the major NP lineages (pitheciids, atelids and cebids), which may have resulted from rapid episodes of adaptive radiation, a question that requires NP divergence time estimates with accurate statistical certainty. In this study, we evaluated the primate timescale focused on the age of nodes of NP radiation. We investigated the performance of complete primate mitochondrial genomes as traditional molecular markers of primate evolution and further including original mitochondrial data from the endangered muriqui, Brachyteles arachnoides (Accession No. {"type":"entrez-nucleotide","attrs":{"text":"JX262672","term_id":"403488686","term_text":"JX262672"}}JX262672). Comparisons of the age estimates at NP nodes based on mitochondrial genomes with those obtained from a nuclear supermatrix showed similar degrees of uncertainty. Further molecular data and more informative calibration priors are required for a more precise understanding of the early NP diversification.     

Reproduction of the Atlantic bobtail squid Sepiola atlantica (Cephalopoda: Sepiolidae) in northwest Spain

Atlantic bobtail squid (Sepiola atlantica) in northwest Spain show seasonal variation in population structure, with juvenile abundance peaking during summer and autumn. However, whether similar patterns exist for reproduction is unknown. Therefore, we describe the reproductive biology of 505 specimens of S. atlantica collected monthly during two consecutive years at two different sites off of Areamilla beach in the Ría de Vigo. Mature males displayed a type of sexual dimorphism previously unknown in members of this species, developing a muscular nodule in the base of each of the ventral arms over ontogeny. Reproductive output of both sexes was similar to that of other bobtail squids. Relative oocyte size (~10% mantle length) appeared to be similar to those of other bobtail squids. Females did not show evidence of having mated before complete maturity. Females of S. atlantica have group‐synchronous ovary maturation, with a positive correlation between female mantle length and ripe oocyte mass, suggesting a terminal investment strategy. Atlantic bobtail squids displayed the same seasonal patterns of reproductive traits at both sampling sites, with significant differences in reproductive activity between males and females. We consider reproductive traits in these small animals as adaptations to the coastal shelf lifestyle.     

Fixational Eye Movement Correction of Blink-Induced Gaze Position Errors

Our eyes move continuously. Even when we attempt to fix our gaze, we produce “fixational” eye movements including microsaccades, drift and tremor. The potential role of microsaccades versus drifts in the control of eye position has been debated for decades and remains in question today. Here we set out to determine the corrective functions of microsaccades and drifts on gaze-position errors due to blinks in non-human primates (Macaca mulatta) and humans. Our results show that blinks contribute to the instability of gaze during fixation, and that microsaccades, but not drifts, correct fixation errors introduced by blinks. These findings provide new insights about eye position control during fixation, and indicate a more general role of microsaccades in fixation correction than thought previously.