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1.
Mar Pollut Bull ; 200: 116096, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340372

RESUMO

Coastal sprawl is among the main drivers of global degradation of shallow marine ecosystems. Among artificial substrates, quarry rock can have faster recruitment of benthic organisms compared to traditional concrete, which is more versatile for construction. However, the factors driving these differences are poorly understood. In this context, this study was designed to compare the intertidal and subtidal benthic and epibenthic assemblages on concrete and artificial basalt boulders in six locations of Madeira Island (northeastern Atlantic, Portugal). To assess the size of the habitat, the shorelines in the study area were quantified using satellite images, resulting in >34 % of the south coast of Madeira being artificial. Benthic assemblages differed primarily between locations and secondarily substrates. Generally, assemblages differed between substrates in the subtidal, with lower biomass and abundance in concrete than basalt. We conclude that these differences are not related to chemical effects (e.g., heavy metals) but instead to a higher detachment rate of calcareous biocrusts from concrete, as surface abrasion is faster in concrete than basalt. Consequently, surface integrity emerges as a factor of ecological significance in coastal constructions. This study advances knowledge on the impact and ecology of artificial shorelines, providing a baseline for future research towards ecological criteria for coastal protection and management.


Assuntos
Ecossistema , Silicatos , Biomassa , Portugal
2.
Mar Pollut Bull ; 198: 115871, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38086107

RESUMO

Non-indigenous species (NIS) spread from marinas to natural environments is influenced by niche availability, habitat suitability, and local biotic resistance. This study explores the effect of indigenous fish feeding behaviour on NIS proliferation using fouling communities, pre-grown on settlement plates, as two distinct, representative models: one from NIS-rich marinas and the other from areas outside marinas with fewer NIS. These plates were mounted on a Remote Video Foraging System (RVFS) near three marinas on Madeira Island. After 24-h, NIS abundance was reduced by 3.5 %. Canthigaster capistrata's preference for marinas plates suggests potential biotic resistance. However, Sparisoma cretense showed equal biting frequencies for both plate types. The cryptogenic ascidian Trididemnum cereum was the preferred target for the fish. Our study introduces a global framework using RVFS for in-situ experiments, replicable across divers contexts (e.g., feeding behaviour, biotic resistance), which can be complemented by metabarcoding and isotopic analysis to confirm consumption patterns.


Assuntos
Espécies Introduzidas , Tetraodontiformes , Animais , Ecossistema , Comportamento Alimentar , Portugal
3.
Mar Pollut Bull ; 187: 114522, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36623468

RESUMO

Marinas are hubs for non-indigenous species (NIS) and constitute the nodes of a network of highly modified water bodies (HMWB) connected by recreational maritime traffic. Floating structures, such as pontoons, are often the surfaces with higher NIS abundance inside marinas and lead the risk for NIS introduction, establishment and spread. However, there is still little information on how the location within the marina and the substratum type can influence the recruitment of fouling assemblages depending on water parameters and substratum chemical composition. In this study, fouling recruitment was studied using an experimental approach with three materials (basalt, concrete and HDPE plastic) in two sites (close and far to the entrance) in two marinas of Madeira Island (NE Atlantic, Portugal). The structure of benthic assemblages after 6- and 12-months colonization, as well as biotic abundance, NIS abundance, richness, diversity, assemblages' volume, biomass and assemblages' morphology were explored. Differences between marinas were the main source of variation for both 6- and 12-month assemblages, with both marinas having different species composition and biomass. The inner and outer sites of both marinas varied in terms of structure and heterogeneity of assemblages and heterogeneity of morphological traits, but assemblages did not differ among substrata. However, basalt had a higher species richness and diversity while concrete showed a higher bioreceptivity in terms of total biotic coverage than the rest of materials. Overall, differences between and within marinas could be related to their structural morphology. This study can be valuable for management of urban ecosystems, towards an increase in the environmental and ecological status of existing marinas and their HMWB and mitigation coastal ecosystems degradation.


Assuntos
Materiais de Construção , Ecossistema , Biomassa , Portugal , Incrustação Biológica , Plásticos
4.
Angew Chem Int Ed Engl ; 61(41): e202210798, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-35943860

RESUMO

Chiral quinacridines react up to four times, step-by-step, with α-diazomalonates under RuII and RhII catalysis. By selecting the catalyst, [CpRu(CH3 CN)3 ][PF6 ] (Cp=cyclopentadienyl) or Rh2 (oct)4 , chemo and regioselective insertions of derived metal carbenes are achieved in favor of mono- or bis-functionalized malonate derivatives, respectively, (r.r.>49 : 1, up to 77 % yield, 12 examples). This multi-introduction of malonate groups is particularly useful to tune optical and chemical properties such as absorption, emission or Brønsted acidity but also cellular bioimaging. Density-functional theory further elucidates the origin of the carbene insertion selectivity and also showcases the importance of conformations in the optical response.


Assuntos
Metano , Ródio , Malonatos , Metano/análogos & derivados , Metano/química , Estrutura Molecular , Ródio/química
5.
Animals (Basel) ; 12(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35565568

RESUMO

Parasitism is among the most common forms of coexistence of organisms of different species. Hemoparasites live in the bloodstream of the host where they complete different life-cycle stages. Members of the phylum Apicomplexa constitute a large portion of all hemoparasites infecting reptiles and their parasite transmitting vectors, including arthropods. In this study, we carried out a survey and molecular identification of hemoparasites in blood samples of the iconic Galápagos marine iguana (Amblyrhynchus cristatus). Major island populations of marine iguanas were sampled to examine large-scale biogeographic patterns of parasite diversity and prevalence. Nested PCRs were used to amplify segments of the 18S rRNA-gene of hemoparasites. Furthermore, ticks attached to marine iguanas were collected and analyzed in the same way to assess their potential use as a non-invasive method for the detection of hemoparasites in vertebrate host species. PCR products were sequenced and a phylogenetic analysis was carried out showing the presence of two genetically distinct clusters of hemoparasites, one more commonly distributed than the other one, belonging to the genera Hepatozoon and/or Hemolivia (Apicomplexa: Eucoccidiorida). Overall, 25% of marine iguanas were infected by hemoparasites. However, infection rates varied strongly among particular island populations (from 3.45% to 50%). Although marine iguanas are an extremely mobile species that has colonized all islands in the Galápagos archipelago, parasite occurrence was not related to geographical distance, suggesting that dispersal behavior has a minor role in parasite transmission. On most islands, females tended to have higher infection rates than males, but this relationship was only significant on one island. Overall, ticks and marine iguanas had similar prevalence and diversity of parasites. However, the infection profiles of ticks and their corresponding hosts (marine iguanas) did not mirror one another, indicating that this method cannot be used reliably to assess marine iguana infection status. Interestingly, we found that hemoparasite prevalence in marine iguanas and ticks tended to be positively correlated across islands. Our results indicate that certain populations of marine iguanas may have special mechanisms and adaptations to cope with parasite infection. In addition, other factors such as vector density, anthropogenic-related activities or the immunological state of marine iguanas could potentially affect the striking variation in hemoparasite prevalence across island populations.

6.
Molecules ; 27(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35408771

RESUMO

Proteins are ubiquitous macromolecules that display a vast repertoire of chemical and enzymatic functions, making them suitable candidates for chemosignals, used in intraspecific communication. Proteins are present in the skin gland secretions of vertebrates but their identity, and especially, their functions, remain largely unknown. Many lizard species possess femoral glands, i.e., epidermal organs primarily involved in the production and secretion of chemosignals, playing a pivotal role in mate choice and intrasexual communication. The lipophilic fraction of femoral glands has been well studied in lizards. In contrast, proteins have been the focus of only a handful of investigations. Here, we identify and describe inter-individual expression patterns and the functionality of proteins present in femoral glands of male sand lizards (Lacerta agilis) by applying mass spectrometry-based proteomics. Our results show that the total number of proteins varied substantially among individuals. None of the identified femoral gland proteins could be directly linked to chemical communication in lizards, although this result hinges on protein annotation in databases in which squamate semiochemicals are poorly represented. In contrast to our expectations, the proteins consistently expressed across individuals were related to the immune system, antioxidant activity and lipid metabolism as their main functions, showing that proteins in reptilian epidermal glands may have other functions besides chemical communication. Interestingly, we found expression of the Major Histocompatibility Complex (MHC) among the multiple and diverse biological processes enriched in FGs, tentatively supporting a previous hypothesis that MHC was coopted for semiochemical function in sand lizards, specifically in mate recognition. Our study shows that mass spectrometry-based proteomics are a powerful tool for characterizing and deciphering the role of proteins secreted by skin glands in non-model vertebrates.


Assuntos
Lagartos , Animais , Humanos , Sistema Imunitário/metabolismo , Metabolismo dos Lipídeos , Lagartos/metabolismo , Masculino , Feromônios/metabolismo , Proteômica
7.
Biochim Biophys Acta Gen Subj ; 1866(5): 130098, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35104623

RESUMO

Our objective was to examine the effects of N-methylacetazolamide (NMA), a non­carbonic anhydrase inhibitor, on ischemia-reperfusion injury. Isolated rat hearts were assigned to the following groups: 1) Non-ischemic control (NIC):110 min of perfusion and 2) Ischemic control (IC): 30 min of global ischemia and 60 min of reperfusion (R). Both groups were repeated in presence of NMA (5 µM), administered during the first 10 min of R. Infarct size (IS) was measured by TTC staining. Developed pressure (LVDP) and end-diastolic pressure (LVEDP) of the left ventricle were used to assess systolic and diastolic function, respectively. The content of P-Akt, P-PKCε, P-Drp1 and calcineurin Aß were measured. In cardiomyocytes the L-type Ca2+ current (ICaL) was recorded with the whole-cell configuration of patch-clamp technique. The addition of NMA to non-ischemic hearts decreased 15% the contractility. In ischemic hearts (IC group), NMA decreased IS (22 ± 2% vs 32 ± 2%, p < 0.05) and improved the post-ischemic recovery of myocardial function. At the end of R, LVDP was 54 ± 7% vs 18 ± 3% and LVEDP was 23 ± 8 vs. 55 ± 7 mmHg ¨p < 0.05¨. The level of P-Akt, P-PKCε and P-Drp1 increased and the expression of calcineurin Aß decreased in NMA treated hearts. Peak ICaL density recorded at 0 mV was smaller in myocytes treated with NMA than in non-treated cells (-1.91 ± 0.15 pA/pF vs -2.32 ± 0.17 pA/pF, p < 0.05). These data suggest that NMA protects the myocardium against ischemia-reperfusion injury through an attenuation of mitochondrial fission by calcineurin/Akt/PKCε-dependent pathways associated to the decrease of ICaL current.


Assuntos
Bloqueadores dos Canais de Cálcio , Cardiotônicos , Metazolamida , Traumatismo por Reperfusão Miocárdica , Animais , Calcineurina , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Cardiotônicos/farmacologia , Metazolamida/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
8.
ACS Org Inorg Au ; 2(1): 53-58, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36855401

RESUMO

An original and straightforward entry to polysubstituted indenes from readily available ynamides is reported. Upon reaction with a N-heterocyclic carbene-gold complex under mild conditions, activated keteniminium ions are generated whose unique electrophilicity triggers a [1,5]-hydride shift and a subsequent cyclization. The presence of an endocyclic enamide in the densely functionalized resulting indenes was shown to be especially useful and versatile, offering a range of opportunities for their further postfunctionalization.

9.
Biochim Biophys Acta Gen Subj ; 1866(2): 130060, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34822923

RESUMO

During menopause women are exposed to an increase in cardiovascular risk. G protein-coupled estrogen receptor (GPER) is known to mediate several of the protective effects of such hormones. G1 was described as a selective and synthetic agonist for GPER. The aim of the present research is to evaluate the effect of a chronic treatment with G1 in ovariectomized (OVX) rats exposed to ischemia/reperfusion (I/R). Considering the hypothesis that an impaired mitochondrial state could be involved in the alterations produced in OVX rats, other objective of this study was to investigate it in an isolated preparation. Three months old rats were assigned to undergo either bilateral ovariectomy or sham operation. The OVX rats were randomly treated during one month with either G1 or vehicle. Cardiac mitochondria from OVX rats showed a depolarized membrane potential and a decreased calcium retention capacity in comparison with Sham rats, which were prevented by chronic G1 treatment. I/R caused a higher decrease of left ventricular developed pressure and a higher increase of left ventricular end diastolic pressure in OVX compared to Sham hearts. These altered mechanical parameters were prevented by G1. The induced infarct size was significantly higher in OVX, which was reduced by G1 treatment. These results indicate that the mitochondrial state in OVX rats is impaired, accompanied by an altered mechanical response after ischemia and reperfusion injury, which was effectively prevented with chronic treatment with G1. The present study may provide further insights for the potential development of a therapy based on the GPER modulation.


Assuntos
Traumatismo por Reperfusão
10.
Sci Rep ; 11(1): 10396, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001926

RESUMO

Despite the relevance of chemical communication in vertebrates, comparative examinations of macroevolutionary trends in chemical signaling systems are scarce. Many turtle and tortoise species are reliant on chemical signals to communicate in aquatic and terrestrial macrohabitats, and many of these species possess specialized integumentary organs, termed mental glands (MGs), involved in the production of chemosignals. We inferred the evolutionary history of MGs and tested the impact of macrohabitat on their evolution. Inference of ancestral states along a time-calibrated phylogeny revealed a single origin in the ancestor of the subclade Testudinoidea. Thus, MGs represent homologous structures in all descending lineages. We also inferred multiple independent losses of MGs in both terrestrial and aquatic clades. Although MGs first appeared in an aquatic turtle (the testudinoid ancestor), macrohabitat seems to have had little effect on MG presence or absence in descendants. Instead, we find clade-specific evolutionary trends, with some clades showing increased gland size and morphological complexity, whereas others exhibiting reduction or MG loss. In sister clades inhabiting similar ecological niches, contrasting patterns (loss vs. maintenance) may occur. We conclude that the multiple losses of MGs in turtle clades have not been influenced by macrohabitat and that other factors have affected MG evolution.


Assuntos
Evolução Biológica , Tegumento Comum/fisiologia , Feromônios/química , Tartarugas/fisiologia , Comunicação Animal , Animais , Fenômenos Biomecânicos , Ecossistema , Tegumento Comum/anatomia & histologia , Feromônios/biossíntese , Filogenia , Transdução de Sinais/genética , Tartarugas/anatomia & histologia
11.
Naturwissenschaften ; 108(1): 7, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528676

RESUMO

Gut microorganisms are crucial for many biological functions playing a pivotal role in the host's well-being. We studied gut bacterial community structure of marine iguana populations across the Galápagos archipelago. Marine iguanas depend heavily on their specialized gut microbiome for the digestion of dietary algae, a resource whose growth was strongly reduced by severe "El Niño"-related climatic fluctuations in 2015/2016. As a consequence, marine iguana populations showed signs of starvation as expressed by a poor body condition. Body condition indices (BCI) varied between island populations indicating that food resources (i.e., algae) are affected differently across the archipelago during 'El Niño' events. Though this event impacted food availability for marine iguanas, we found that reductions in body condition due to "El Niño"-related starvation did not result in differences in bacterial gut community structure. Species richness of gut microorganisms was instead correlated with levels of neutral genetic diversity in the distinct host populations. Our data suggest that marine iguana populations with a higher level of gene diversity and allelic richness may harbor a more diverse gut microbiome than those populations with lower genetic diversity. Since low values of these diversity parameters usually correlate with small census and effective population sizes, we use our results to propose a novel hypothesis according to which small and genetically less diverse host populations might be characterized by less diverse microbiomes. Whether such genetically depauperate populations may experience additional threats from reduced dietary flexibility due to a limited intestinal microbiome is currently unclear and calls for further investigation.


Assuntos
El Niño Oscilação Sul , Microbioma Gastrointestinal/fisiologia , Iguanas/microbiologia , Animais , Biodiversidade , Equador
12.
Arch Biochem Biophys ; 694: 108600, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33007282

RESUMO

Physical training stimulates the development of physiologic cardiac hypertrophy (CH), being a key event in this process the inhibition of the Na+/H+ exchanger. However, the role of the sodium bicarbonate cotransporter (NBC) has not been explored yet under this circumstance. C57/Bl6 mice were allowed to voluntary exercise (wheel running) for five weeks. Cardiac mass was evaluated by echocardiography and histomorphometry detecting that training promoted the development of physiological CH (heart weight/tibia length ratio, mg/mm: 6.54 ± 0.20 vs 8.81 ± 0.24; interstitial collagen content, %: 3.14 ± 0.63 vs. 1.57 ± 0.27; and cross-sectional area of cardiomyocytes, µm2: 200.6 ± 8.92 vs. 281.9 ± 24.05; sedentary (Sed) and exercised (Ex) mice, respectively). The activity of the electrogenic isoform of the cardiac NBC (NBCe1) was estimated by recording intracellular pH under high potassium concentration and by measuring action potential duration (APD). NBCe1 activity was significantly increased in isolated cardiomyocytes of trained mice. Additionally, the APD was shorter and the alkalization due to high extracellular potassium-induced depolarization was greater in this group, indicating that the NBCe1 was hyperactive. These results are online with the observed myocardial up-regulation of the NBCe1 (Western Blot, %: 100 ± 13.86 vs. 202 ± 29.98; Sed vs. Ex, n = 6 each group). In addition, we detected a reduction in H2O2 production in the myocardium of trained mice. These results support that voluntary training induces the development of physiologic CH with up-regulation of the cardiac NBCe1 in mice. Furthermore, the improvement in the antioxidant capacity contributes to the beneficial cardiovascular consequences of physical training.


Assuntos
Miocárdio/metabolismo , Condicionamento Físico Animal , Simportadores de Sódio-Bicarbonato/metabolismo , Animais , Cardiomegalia Induzida por Exercícios/fisiologia , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Isoformas de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
13.
Mol Cell Proteomics ; 19(9): 1523-1532, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32581039

RESUMO

Communication between individuals via molecules, termed chemosignaling, is widespread among animal and plant species. However, we lack knowledge on the specific functions of the substances involved for most systems. The femoral gland is an organ that secretes a waxy substance involved in chemical communication in lizards. Although the lipids and volatile substances secreted by the femoral glands have been investigated in several biochemical studies, the protein composition and functions of secretions remain completely unknown. Applying a proteomic approach, we provide the first attempt to comprehensively characterize the protein composition of femoral gland secretions from the Galápagos marine iguana. Using samples from several organs, the marine iguana proteome was assembled by next-generation sequencing and MS, resulting in 7513 proteins. Of these, 4305 proteins were present in the femoral gland, including keratins, small serum proteins, and fatty acid-binding proteins. Surprisingly, no proteins with discernible roles in partner recognition or inter-species communication could be identified. However, we did find several proteins with direct associations to the innate immune system, including lysozyme C, antileukoproteinase (ALP), pulmonary surfactant protein (SFTPD), and galectin (LGALS1) suggesting that the femoral glands function as an important barrier to infection. Furthermore, we report several novel anti-microbial peptides from the femoral glands that show similar action against Escherichia coli and Bacillus subtilis such as oncocin, a peptide known for its effectiveness against Gram-negative pathogens. This proteomics data set is a valuable resource for future functional protein analysis and demonstrates that femoral gland secretions also perform functions of the innate immune system.


Assuntos
Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Iguanas/metabolismo , Sistema Imunitário/metabolismo , Imunidade Inata , Proteoma/metabolismo , Transcriptoma , Animais , Apoproteínas/genética , Apoproteínas/metabolismo , Bacillus subtilis/efeitos dos fármacos , Encéfalo/metabolismo , Fatores Quimiotáticos/genética , Fatores Quimiotáticos/metabolismo , Equador , Endopeptidases/genética , Endopeptidases/metabolismo , Escherichia coli/efeitos dos fármacos , Galectinas/genética , Galectinas/metabolismo , Coração/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Iguanas/genética , Iguanas/imunologia , Imunidade Inata/genética , Pulmão/metabolismo , Muramidase/genética , Muramidase/metabolismo , Músculos/metabolismo , Miocárdio/metabolismo , Especificidade de Órgãos , Proteoma/genética , Proteoma/imunologia , Proteômica , Proteínas Associadas a Surfactantes Pulmonares/genética , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Pele/metabolismo , Espectrometria de Massas em Tandem , Transcriptoma/genética
14.
PeerJ ; 8: e9047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32461828

RESUMO

Despite evidence from anatomy, behavior and genomics indicating that the sense of smell in turtles is important, our understanding of chemical communication in this group is still rudimentary. Our aim was to describe the microanatomy of mental glands (MGs) in a freshwater turtle, Mauremys leprosa (Geoemydidae), and to assess the chemical composition of their secretions with respect to variation among individuals and between sexes. MGs are paired sac-like organs on the gular region of the neck and are dimorphic in this species with males having fully functional holocrine glands while those of females appear non-secretory and vestigial. In adult males, the glandular epithelium of the inner portion of the gland provides exocytotic products as well as cellular debris into the lumen of the gland. The contents of the lumen can be secreted through the narrow duct portion of the gland ending in an orifice on the surface of the skin. Females have invaginated structures similar in general outline to male glands, but lack a glandular epithelium. Using gas chromatography coupled to mass spectrometry, we identified a total of 61 compounds in mental gland secretions, the most numerous being carboxylic acids, carbohydrates, alkanes, steroids and alcohols. The number of compounds per individual varied widely (mean (median) ± SD = 14.54 (13) ± 8.44; min = 3; max = 40), but only cholesterol was found in all samples. We found that the relative abundances of only six chemicals were different between the sexes, although males tended to have larger amounts of particular compounds. Although the lipid fraction of mental gland secretions is rich in chemical compounds, most occur in both sexes suggesting that they are metabolic byproducts with no role in chemical signaling. However, the relative amounts of some compounds tended to be higher in males, with significantly larger amounts of two carboxylic acids and one steroid, suggesting their putative involvement in chemical communication.

15.
Chem Sci ; 12(4): 1479-1485, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34163911

RESUMO

Hexahydropyrazinoindoles were prepared in a single step from N-sulfonyl triazoles and imidazolidines. Under dirhodium catalysis, α-imino carbenes were generated and formed nitrogen ylide intermediates that, after subsequent aminal opening, afforded the pyrazinoindoles predominantly via formal [1,2]-Stevens and tandem Friedel-Crafts cyclizations. Of mechanistic importance, a regiodivergent reactivity was engineered through the use of a specific unsymmetrically substituted imidazolidine that promoted the exclusive formation of 8-membered ring 1,3,6-triazocines. Based on DFT calculations, an original Curtin-Hammett-like situation was demonstrated for the mechanism. Further derivatizations led to functionalized tetrahydropyrazinoindoles in high yields.

16.
Pflugers Arch ; 472(1): 103-115, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31754830

RESUMO

The soluble adenylyl cyclase (sAC) was identified in the heart as another source of cyclic AMP (cAMP). However, its cardiac physiological function is unknown. On the other hand, the cardiac Na+/HCO3- cotransporter (NBC) promotes the cellular co-influx of HCO3- and Na+. Since sAC activity is regulated by HCO3-, our purpose was to investigate the potential functional relationship between NBC and sAC in the cardiomyocyte. Rat ventricular myocytes were loaded with Fura-2, Fluo-3, or BCECF to measure Ca2+ transient (Ca2+i) by epifluorescence, Ca2+ sparks frequency (CaSF) by confocal microscopy, or intracellular pH (pHi) by epifluorescence, respectively. Sarcomere or cell shortening was measured with a video camera as an index of contractility. The NBC blocker S0859 (10 µM), the selective inhibitor of sAC KH7 (1 µM), and the PKA inhibitor H89 (0.1 µM) induced a negative inotropic effect which was associated with a decrease in Ca2+i. Since PKA increases Ca2+ release through sarcoplasmic reticulum RyR channels, CaSF was measured as an index of RyR open probability. The generation of CaSF was prevented by KH7. Finally, we investigated the potential role of sAC activation on NBC activity. NBC-mediated recovery from acidosis was faster in the presence of KH7 or H89, suggesting that the pathway sAC-PKA is negatively regulating NBC function, consistent with a negative feedback modulation of the HCO3- influx that activates sAC. In summary, the results demonstrated that the complex NBC-sAC-PKA plays a relevant role in Ca2+ handling and basal cardiac contractility.


Assuntos
Adenilil Ciclases/metabolismo , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Inibidores de Adenilil Ciclases/farmacologia , Animais , Benzamidas/farmacologia , Sinalização do Cálcio , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Ventrículos do Coração/citologia , Isoquinolinas/farmacologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Ratos , Ratos Wistar , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Simportadores de Sódio-Bicarbonato/antagonistas & inibidores , Sulfonamidas/farmacologia
17.
J Am Heart Assoc ; 8(7): e011066, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30917747

RESUMO

Background It is well known that after menopause women are exposed to a greater cardiovascular risk, but the intracellular modifications are not properly described. The sodium/proton exchanger (NHE) and the sodium/bicarbonate cotransporter (NBC) regulate the intracellular pH and, indirectly, the intracellular sodium concentration ([Na+]). There are 2 isoforms of NBC in the heart: the electrogenic (1Na+/2[Formula: see text]; NBCe1) and the electroneutral (1Na+/1[Formula: see text]; NBCn1). Because NHE and NBCn1 hyperactivity as well as the NBCe1 decreased activity have been associated with several cardiovascular pathologies, the aim of this study was to investigate the potential alterations of the alkalinizing transporters during the postmenopausal period. Methods and Results Three-month ovariectomized rats (OVX) were used. The NHE activity and protein expression are significantly increased in OVX. The NBCe1 activity is diminished, and the NBCn1 activity becomes predominant in OVX rats. p-Akt levels showed a significant diminution in OVX. Finally, NHE activity in platelets from OVX rats is also higher in comparison to sham rats, resulting in a potential biomarker of cardiovascular diseases. Conclusions Our results demonstrated for the first time that in the cardiac ventricular myocytes of OVX rats NHE and NBC isoforms are altered, probably because of the decreased level of p-Akt, compromising the ionic intracellular homeostasis.


Assuntos
Miócitos Cardíacos/fisiologia , Ovariectomia , Acidose/fisiopatologia , Animais , Feminino , Concentração de Íons de Hidrogênio , Hipertensão/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Simportadores de Sódio-Bicarbonato/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo
18.
Eur Heart J ; 40(7): 621-631, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30476079

RESUMO

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.


Assuntos
Algoritmos , Doenças Cardiovasculares/etiologia , Idoso , Calibragem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco
19.
Behav Processes ; 157: 142-147, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30157465

RESUMO

Animals respond to predation risk with antipredatory behaviours that may disclose the presence of different personality traits among individuals in a population, and how populations may differ for the expression of those traits. Variation among individuals is a necessary condition for the evolution through natural selection and inter-individual behavioural differences may be selected in different environmental situations. We tested whether individuals of two freshwater turtle species, Emys orbicularis and Mauremys leprosa, show consistent risk-taking behaviour when exposed to the presence of a potential predator. In an outdoor experimental setting, we simulated a predatory attack by overturning a turtle onto its carapace and recording three different behavioural response variables. Our results showed clear differences between species. The appearance time was highly consistent over the trials for both species, but was shorter for E. orbicularis and very long for M. leprosa. Waiting time was consistent only for females of E. orbicularis while M. leprosa did not show repeatability and had significantly longer waiting times. The number of failed righting attempts, likely being partially dependent on turtle individual performance, was highly consistent during the experiment for both species. The hiding behaviour in both species of freshwater turtles was consistent over time and, therefore, could be regarded as a personality trait. However, the differences in waiting times consistency suggested possible differences in defensive strategies between sexes and species.


Assuntos
Comportamento Predatório , Tartarugas , Animais , Feminino , Água Doce , Individualidade , Masculino , Personalidade , Especificidade da Espécie
20.
Angew Chem Int Ed Engl ; 57(24): 7151-7155, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29673027

RESUMO

Polycyclic indoline-benzodiazepines can be accessed through the intermolecular reaction of Tröger bases with N-sulfonyl-1,2,3-triazoles. Under RhII catalysis, α-imino carbenes are generated and a subsequent cascade of [1,2]-Stevens, Friedel-Crafts, Grob, and aminal formation reactions yield the polycyclic heterocycles as single isomers (d.r.>49:1, four stereocenters including two bridgehead N atoms). Further ring expansion by insertion of a second α-imino carbene leads to elaborated polycyclic 9-membered-ring triazonanes.


Assuntos
Benzodiazepinas/síntese química , Indóis/síntese química , Compostos Policíclicos/síntese química , Benzodiazepinas/química , Catálise , Iminas/química , Indóis/química , Metano/análogos & derivados , Metano/química , Modelos Moleculares , Compostos Policíclicos/química , Ródio/química , Estereoisomerismo , Triazóis/química
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