RESUMO
Leukocyte rolling adhesion, facilitated by selectin-mediated interactions, is a highly dynamic process in which cells roll along the endothelial surface of blood vessel walls to reach the site of infection. The most common approach to investigate cell-substrate adhesion is to analyze the cell rolling velocity in response to shear stress changes. It is assumed that changes in rolling velocity indicate changes in adhesion strength. In general, cell rolling velocity is studied at the population level as an average velocity corresponding to given shear stress. However, no statistical investigation has been performed on the instantaneous velocity distribution. In this study, we first developed a method to remove systematic noise and revealed the true velocity distribution to exhibit a log-normal profile. We then demonstrated that the log-normal distribution describes the instantaneous velocity at both the population and single-cell levels across the physiological flow rates. The log-normal parameters capture the cell motion more accurately than the mean and median velocities, which are prone to systematic error. Lastly, we connected the velocity distribution to the molecular adhesion force distribution and showed that the slip-bond regime of the catch-slip behavior of the P-selectin/PSGL-1 interaction is responsible for the variation of cell velocity.
Assuntos
Selectina L , Selectina-P , Adesão Celular , Migração e Rolagem de Leucócitos , Neutrófilos , Estresse MecânicoRESUMO
Considerable uncertainty remains over how increasing atmospheric CO2 and anthropogenic climate changes are affecting open-ocean marine ecosystems from phytoplankton to top predators. Biological time series data are thus urgently needed for the world's oceans. Here, we use the carbon stable isotope composition of tuna to provide a first insight into the existence of global trends in complex ecosystem dynamics and changes in the oceanic carbon cycle. From 2000 to 2015, considerable declines in δ13 C values of 0.8-2.5 were observed across three tuna species sampled globally, with more substantial changes in the Pacific Ocean compared to the Atlantic and Indian Oceans. Tuna recorded not only the Suess effect, that is, fossil fuel-derived and isotopically light carbon being incorporated into marine ecosystems, but also recorded profound changes at the base of marine food webs. We suggest a global shift in phytoplankton community structure, for example, a reduction in 13 C-rich phytoplankton such as diatoms, and/or a change in phytoplankton physiology during this period, although this does not rule out other concomitant changes at higher levels in the food webs. Our study establishes tuna δ13 C values as a candidate essential ocean variable to assess complex ecosystem responses to climate change at regional to global scales and over decadal timescales. Finally, this time series will be invaluable in calibrating and validating global earth system models to project changes in marine biota.
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Fitoplâncton , Atum , Animais , Isótopos de Carbono , Ecossistema , Oceano Índico , Oceanos e Mares , Oceano PacíficoRESUMO
The excitatory neurotransmitter glutamate evokes physiological responses within the astrocytic network that lead to fine morphological changes. However, the mechanism by which astrocytes couple glutamate sensing with cellular calcium rise remains unclear. We tested a possible connection between L-type voltage-gated calcium channels (Cav) and glutamate-induced response in U118-MG astrocytoma cells. While astrocytoma cells differ from primary astrocytes, they demonstrate the same response to glutamate. In this study, the extension of U118-MG processes upon glutamate exposure was shown to depend on extracellular calcium entry via L-type Cav's. Drugs known to bind to the pore-forming subunit of Cav's decreased the astrocytic filopodia extension caused by glutamate, and ligands of the α2δ auxiliary subunit inhibited all process growth (e.g., gabapentinoids). The observed phenotypic responses suggest that α2δ is a main contributor to the role of Cavs in glutamate-dependent filopodiagenesis, thereby opening new avenues of research on the role of α2δ in astrocytic neurochemical signaling.
Assuntos
Astrócitos/metabolismo , Astrocitoma/metabolismo , Canais de Cálcio Tipo L/metabolismo , Cálcio/metabolismo , Astrocitoma/patologia , Ácido Glutâmico/metabolismo , Humanos , Subunidades Proteicas/metabolismo , Transdução de Sinais/fisiologia , Transmissão Sináptica/fisiologiaRESUMO
A unified stereoselective synthesis of 4-substituted kainoids is reported. Four kainic acid analogues were obtained in 8-11 steps with up to 54% overall yields. Starting from trans-4-hydroxy-l-proline, the sequence enables a late-stage modification of C4 substituents with sp2 nucleophiles. Stereoselective steps include a cerium-promoted nucleophilic addition and a palladium-catalyzed reduction. A 10-step route to acid 21a was also established to enable ready functionalization of the C4 position.
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This study examined the fatty acid composition of three sympatric tropical tuna species (bigeye Thunnus obesus, yellowfin T. albacares and skipjack tuna Kastuwonus pelamis) sampled in the Western Indian Ocean in 2013. The fatty acid compositions of neutral and polar lipids, respectively involved in energy storage and cell membrane structure, were explored and compared in four tissues (red and white muscles, liver and gonads), according to biological (size, sex and maturity) and environmental (season and area) factors. The liver and the red muscle were the fattest tissues (i.e., higher levels of storage lipids) in all species and polar lipids were the lowest in the white muscle. Species and tissue types explained most differences in fatty acid compositions, while environmental factors had limited effects, except in the hepatic cell membrane where fatty acid composition varied with monsoons. Docosahexaenoic acid (22:6n-3) was the major fatty acid in both polar and neutral lipid fractions, especially in muscles. Eicosapentaenoic acid (20:5n-3) and oleic acid (18:1n-9) were in higher proportion in neutral than in polar lipids. Arachidonic acid (20:4n-6) and 22:6n-3, together with docosapentaenoic acid (22:5n-6) and stearic acid (18:0), showed preferential accumulation in polar lipids. 20:4n-6 was particularly involved in cell membranes of ovary and white muscle. Overall, an important inter-individual variability in fatty acid compositions of structural lipids was found within tissue types despite considering biological factors that are most likely to influence this type of lipids. It suggests that fatty acid profiles are influenced by individual-specific behaviors.
Assuntos
Ácidos Graxos/metabolismo , Atum/metabolismo , Animais , Cromatografia GasosaRESUMO
RATIONALE: The bias associated with lipid contents in fish tissues is a recalcitrant topic for trophic studies using stable isotopes. Lipids are depleted in the heavy carbon isotope ((13)C) and the lipid content varies considerably among species, tissues and in both time and space. We have applied and assessed different correction methods for tropical tuna tissues. METHODS: We tested two types of normalization methods to deal with variable lipid content in liver, gonads, and white and red muscles of yellowfin, bigeye and skipjack tuna: a chemical extraction using dichloromethane and a mathematical correction based on three modeling approaches (linear, non-linear and mass balance models). We measured isotopic ratios of bulk and lipid-free tissues and assessed the predictive ability of the correction models with the lipid-free measurements. The parameters of the models were estimated from our dataset and from results from published studies on other species. RESULTS: Comparison between bulk, lipid-free and lipid-corrected isotopic ratios demonstrated that (1) chemical extraction using dichloromethane did not affect δ(15)N values; (2) the change in δ(13)C values after extraction was tissue-specific; (3) lipid-normalization models using published parameter estimates failed to predict lipid-corrected δ(13)C values; and (4) linear and non-linear models using parameters estimated for each tissue from our dataset provided accurate δ(13)C predictions for all tissues, and mass balance model for white muscle only. CONCLUSIONS: Models using published estimates for parameters from other species cannot be used. Based on a range of lipid content that do not exceed 45%, we recommend the linear model to correct the bulk δ(13)C values in the investigated tissues but the parameters have to be estimated from a proportion of the original data for which chemical extraction is required and the isotopic values of bulk and lipid-free tissues are measured.
Assuntos
Isótopos de Carbono/análise , Lipídeos/análise , Isótopos de Nitrogênio/análise , Atum , Animais , Fracionamento Químico , Feminino , Proteínas de Peixes/análise , Oceano Índico , Lipídeos/isolamento & purificação , Fígado/química , Masculino , Espectrometria de Massas/métodos , Modelos Teóricos , Músculo Esquelético/química , Clima TropicalRESUMO
Since 2011, the Caribbean coasts have been subject to episodic influxes of floating Sargassum seaweed of unprecedented magnitude originating from a new area "the Great Atlantic Sargassum Belt" (GASB), leading in episodic influxes and mass strandings of floating Sargassum. For the biofilm of both holopelagic and benthic Sargassum as well as in the surrounding waters, we characterized the main functional groups involved in the microbial nitrogen cycle. The abundance of genes representing nitrogen fixation (nifH), nitrification (amoA), and denitrification (nosZ) showed the predominance of diazotrophs, particularly within the GASB and the Sargasso Sea. In both location, the biofilm associated with holopelagic Sargassum harboured a more abundant proportion of diazotrophs than the surrounding water. The mean δ15N value of the GASB seaweed was very negative (-2.04), and lower than previously reported, reinforcing the hypothesis that the source of nitrogen comes from the nitrogen-fixing activity of diazotrophs within this new area of proliferation. Analysis of the diversity of diazotrophic communities revealed for the first time the predominance of heterotrophic diazotrophic bacteria belonging to the phylum Proteobacteria in holopelagic Sargassum biofilms. The nifH sequences belonging to Vibrio genus (Gammaproteobacteria) and Filomicrobium sp. (Alphaproteobacteria) were the most abundant and reached, respectively, up to 46.0% and 33.2% of the community. We highlighted the atmospheric origin of the nitrogen used during the growth of holopelagic Sargassum within the GASB and a contribution of heterotrophic nitrogen-fixing bacteria to a part of the Sargassum proliferation.
Assuntos
Sargassum , Bactérias/genética , Fixação de Nitrogênio/genética , Nitrogênio , Proliferação de CélulasRESUMO
Plastic debris is ubiquitous in the hydrosphere. Yet, we lack an understanding of contamination among deep-sea species and primarily how each trait can influence microplastic intake. We investigated microplastic contamination in the digestive tract of hyper-abundant mesopelagic lanternfishes (n = 364 individuals) from the Southwestern Tropical Atlantic, captured from 90 to 1000 m depth. Overall, microplastics were detected in most individuals analysed (frequency of occurrence = 68 %). Large microplastics, mostly of a filamentous shape were the most frequent, followed by smaller fragments and foams. Microplastics made of high-density polymers (PET, PVC, PA, SBR rubber) were more prevalent than low-density ones (PE, EVA and PBD rubber), especially under deeper layers. Larger microplastics were detected in lanternfishes captured off the northeastern Brazilian coast (mean 0.88 ± SE 0.06 mm) compared to those from around the Rocas Atoll and Fernando de Noronha Archipelago (0.70 ± 0.07 mm; p≤ 0.05), â¼350 km from the continent. Moreover, lanternfishes that migrate from the upper mesopelagic (200-500 m) to the epipelagic layers (<200 m) had simultaneously the highest intake and the smallest particles (1.65 ± 0.17 particles individual-1 and 0.55 ± 0.07 mm; p≤ 0.05). Biological mediated transport of microplastics from the epipelagic to the mesopelagic waters was evinced, but fishes foraging in shallower layers had the lowest intake (1.11 ± 0.10 part. ind.-1; p≤ 0.05). Furthermore, the jaw length was positively associated with an increment in microplastic intake (Incidence Rate Ratio = 1.1; p≤ 0.05). The lanternfishes that preferably prey upon fish larvae are more prone to microplastic intake than their counterparts, which forage mostly on crustaceans and gelatinous zooplankton (p≤ 0.05).
Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Plásticos , Borracha , Peixes , Polímeros , Monitoramento Ambiental , Poluentes Químicos da Água/análiseRESUMO
The connection between epipelagic and deep-sea mesopelagic realms controls a variety of ecosystem processes including oceanic carbon storage and the provision of harvestable fish stocks. So far, these two layers have been mostly addressed in isolation and the ways they connect remain poorly understood. Furthermore, both systems are affected by climate change, exploitation of resources, and increasing pervasion of pollutants. Here we use bulk isotopes of δ13C and δ15N of 60 ecosystem components to evaluate the trophic linkage between epipelagic and mesopelagic ecosystems in warm oligotrophic waters. Additionally, we we conducted a comparison of isotopic niche sizes and overlaps across multiple species to evaluate how environmental gradients between epipelagic and mesopelagic ecosystems shape ecological patterns of resource use and competition between species. Our database comprises siphonophores, crustaceans, cephalopods, salpas, fishes, and seabirds. It also includes five zooplankton size classes, two groups of fish larvae, and particulate organic matter collected at different depths. Through this wide taxonomic and trophic variety of epipelagic and mesopelagic species, we show that pelagic species access resources originating from different food sources, mostly autotrophic-based (epipelagics) and microbial heterotrophic-based (mesopelagics). This leads to a sharp trophic dissimilarity between vertical layers. Additionally, we show that trophic specialization increases in deep-sea species and argue that food availability and environmental stability are among the main drivers of this pattern. Finally, we discuss how the ecological traits of pelagic species highlighted in this study can respond to human impacts and increase their vulnerability in the Anthropocene.
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Ecossistema , Peixes , Animais , Humanos , Oceanos e Mares , Zooplâncton , Estado Nutricional , Cadeia AlimentarRESUMO
Astrocytes are non-excitable cells in the CNS that can cause life-threatening astrocytoma tumors when they transform to cancerous cells. Perturbed homeostasis of the neurotransmitter glutamate is associated with astrocytoma tumor onset and progression, but the factors that govern this phenomenon are less known. Herein, we review possible mechanisms by which glutamate may act in facilitating the growth of projections in astrocytic cells. This review discusses the similarities and differences between the morphology of astrocytes and astrocytoma cells, and the role that dysregulation in glutamate and calcium signaling plays in the aberrant morphology of astrocytoma cells. Converging reports suggest that ionotropic glutamate receptors and voltage-gated calcium channels expressed in astrocytes may be responsible for the abnormal filopodiagenesis or process extension leading to astrocytoma cells' infiltration throughout the brain.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Astrócitos/patologia , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Ácido Glutâmico , Humanos , Transdução de SinaisRESUMO
PURPOSE: In the brain, astrocytes are non-excitable cells that undergo rapid morphological changes when stimulated by the excitatory neurotransmitter glutamate. We developed a chemical probe to monitor how glutamate affects the density and distribution of astrocytic L-type voltage-gated calcium channels (LTCC). PROCEDURES: The imaging probe FluoBar1 was created from a barbiturate ligand modified with a fluorescent coumarin moiety. The probe selectivity was examined with colocalization analyses of confocal fluorescence imaging in U118-MG and transfected COS-7 cells. Living cells treated with 50 nM FluoBar1 were imaged in real time to reveal changes in density and distribution of astrocytic LTCCs upon exposure to glutamate. RESULTS: FluoBar1 was synthesized in ten steps. The selectivity of the probe was demonstrated with immunoblotting and confocal imaging of immunostained cells expressing the CaV1.2 isoform of LTCCs proteins. Applying FluoBar1 to astrocyte model cells U118-MG allowed us to measure a fivefold increase in fluorescence density of LTCCs upon glutamate exposure. CONCLUSIONS: Imaging probe FluoBar1 allows the real-time monitoring of LTCCs in living cells, revealing for first time that glutamate causes a rapid increase of LTCC membranar density in astrocyte model cells. FluoBar1 may help tackle previously intractable questions about LTCC dynamics in cellular events.
Assuntos
Astrócitos/citologia , Astrócitos/metabolismo , Encéfalo/metabolismo , Canais de Cálcio Tipo L/química , Ácido Glutâmico/metabolismo , Sondas Moleculares/química , Animais , Células COS , Cálcio/metabolismo , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Imuno-Histoquímica , Ligantes , Microscopia Confocal , Neurotransmissores , Transdução de Sinais , TransfecçãoRESUMO
Hyaluronic acid is a native extra-cellular matrix derivative that promises unique properties, such as anti-inflammatory response and cell-signaling with tissue-specific applications under its bioactive properties. Here, we investigate the importance of the duration of synthesis to obtain photocrosslinkable methacrylated hyaluronic acid (MeHA) with high degree of substitution. MeHA with high degree of substitution can result in rapid photocrosslinking and can be used as a bioink for stereolithographic (SLA) three dimensional 3D bioprinting. Increased degree of substitution results Our findings show that a ten-day synthesis results in an 88% degree of methacrylation (DM), whereas three-day and five-day syntheses result in 32% and 42% DM, respectively. The rheological characterization revealed an increased rate of photopolymerization with increasing DM. Further, we developed a hybrid bioink to overcome the non-cell-adhesive nature of MeHA by combining it with gelatin methacryloyl (GelMA) to fabricate 3D cell-laden hydrogel scaffolds. The hybrid bioink exhibited a 55% enhancement in stiffness compared to MeHA only and enabled cell-adhesion while maintaining high cell viability. Investigations also revealed that the hybrid bioink was a more suitable candidate for stereolithography (SLA) 3D bioprinting than MeHA because of its mechanical strength, printability, and cell-adhesive nature. This research lays out a firm foundation for the development of a stable hybrid bioink with MeHA and GelMA for first-ever use with SLA 3D bioprinting.
Assuntos
Bioimpressão , Gelatina , Ácido Hialurônico , Hidrogéis , Impressão Tridimensional , Estereolitografia , Engenharia Tecidual , Alicerces TeciduaisRESUMO
We used complementary stable isotope (SIA) and stomach content (SCA) analyses to investigate feeding relationships among species of the nektobenthic communities and the potential ecological effects of the bottom trawling of a coastal ecosystem in northeastern Brazil. Carbon (δ13C) and nitrogen (δ15N) compositions were determined for five basal sources and 28 consumers, from zooplankton to shrimp and fish species. Fishes and basal sources showed a broad range of δ15N (fishes: 6.49-14.94; sources: 2.58-6.79) and δ13C values (fishes: -23.86 to -13.71; sources: -24.32 to -13.53), while shrimps and crabs exhibited similar nitrogen and carbon ratios. Six trophic consumer groups were determined among zooplankton, crustaceans and fishes by SIA, with trophic pathways associated mostly with benthic sources. SCA results indicated a preference for benthic invertebrates, mainly worms, crabs and shrimps, as prey for the fish fauna, highlighting their importance in the food web. In overall, differences between SCA and the SIA approaches were observed, except for groups composed mainly for shrimps and some species of high δ15N values, mostly piscivorous and zoobenthivores. Given the absence of regulation for bottom trawling activities in the area, the cumulative effects of trawling on population parameters, species composition, potentially decreasing the abundance of benthic preys (e.g., shrimps, worms and crabs) may lead to changes in the trophic structure potentially affect the food web and the sustainability of the fishery.
Assuntos
Pesqueiros/estatística & dados numéricos , Animais , Brasil , Isótopos de Carbono/análise , Peixes , Cadeia Alimentar , Invertebrados , Isótopos de Nitrogênio/análise , ZooplânctonRESUMO
Nitrogen and carbon stable isotope data sets are commonly used to assess complex population to ecosystem responses to natural or anthropogenic changes at regional to global spatial scales, and monthly to decadal timescales. Measured in the tissues of consumers, nitrogen isotopes (δ15 N) are primarily used to estimate trophic position while carbon isotopes (δ13 C) describe habitat associations and feeding pathways. Models of both δ15 N and δ13 C values and their associated variance can be used to estimate likely dietary contributions and niche width and provide inferences about consumer movement and migration. Stable isotope data have added utility when used in combination with other empirical data sets (e.g., stomach content, movement tracking, bioregionalization, contaminant, or fisheries data) and are increasingly relied upon in food web and ecosystem models. While numerous regional studies publish tables of mean δ15 N and δ13 C values, limited individual records have been made available for wider use. Such a deficiency has impeded full utility of the data, which otherwise would facilitate identification of macroscale patterns. The data provided here consist of 4,498 records of individuals of three tuna species, Thunnus alalunga, T. obesus, and T. albacares sampled from all major ocean basins from 2000 to 2015. For each individual tuna, we provide a record of the following: species name, sampling date, sampling location, tuna length, muscle bulk and baseline corrected δ15 N values, and muscle bulk and, where available, lipid corrected δ13 C values. We provide these individual records to support comparative studies and more robust modeling projects seeking to improve understanding of complex marine ecosystem dynamics and their responses to a changing environment. There are no copyright restrictions for research and/or teaching purposes. Users are requested to acknowledge their use of the data in publications, research proposals, websites, and other outlets following the citation instructions in Class III, Section B.
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A highly enantioselective desymmetrization of meso cyclopent-2-ene-1,4-diethyl dicarbonates has been developed using a Rh-catalyzed asymmetric allylic substitution. Depending on the type of ligand used, each of two regioisomeric products can be obtained in good yield and excellent enantioselectivity. Under rhodium(I) catalysis, bisphosphine P-Phos ligands form trans-1,2-arylcyclopentenols as the major product, whereas Segphos ligands lead predominantly to trans-1,4-arylcyclopentenols.
Assuntos
Ácidos Borônicos/química , Ródio/química , Catálise , Ciclização , Ligantes , Estrutura Molecular , EstereoisomerismoRESUMO
Mesopelagic fishes are numerically the most important vertebrate group of all world's oceans. While these species are increasingly threatened by anthropogenic activities, basic biological knowledge is still lacking. For instance, major uncertainties remain on the behaviour, ecology, and thus functional roles of mesopelagic micronektivores, particularly regarding their interactions with physicochemical features. Here, we examine the trophic ecology, habitat, and migratory behaviour of the viperfish (Chauliodus sloani)-a poorly known and abundant deep-sea species-to further understand the ecology and thus functional role of mesopelagic micronektivores. Moreover, we explore how physical drivers may affect these features and how these relationships are likely to change over large oceanic areas. The viperfish heavily preys on epipelagic migrant species, especially myctophids, and presents spatial and trophic ontogenetic shifts. Temperature restricts its vertical distribution. Therefore, its trophodynamics, migratory behaviour, and functional roles are expected to be modulated by the latitudinal change in temperature. For instance, in most tropical regions the viperfish stay full-time feeding, excreting, and serving as prey (e.g. for bathypelagic predators) at deep layers. On the contrary, in temperate regions, the viperfish ascend to superficial waters where they trophically interact with epipelagic predators and may release carbon where its remineralization is the greatest.
Assuntos
Migração Animal , Peixes , Animais , Ecologia , Ecossistema , Peixes/fisiologia , Oceanos e Mares , Dinâmica PopulacionalRESUMO
Since 2011, huge amounts of Sargassum algae are detected in the equatorial Atlantic, causing large strandings events on the coasts of the West Indies, Brazil and West Africa. The distribution of this stock shows strong annual and interannual variability, whose drivers are not settled yet. Here we use satellite Sargassum observations from MODIS and currents from an ocean reanalysis to simulate the passive transport of algae in 2017. Wind effect was necessary to fit the observed distribution. Simulations reasonably reproduce the satellite monthly distribution for up to seven months, confirming the prominent role of transport in the distribution cycle. Annual cycle appears as a zonal exchange between eastern (EAR) and western accumulation regions (WAR). EAR is well explained by advection alone, with sharp meridional distribution controlled by converging currents below the inter-tropical Convergence Zone. Instead, WAR is not explained by advection alone, suggesting local growth.
Assuntos
Sargassum , Oceano Atlântico , Brasil , Índias Ocidentais , VentoRESUMO
Historically, pelagic Sargassum were only found in the Sargasso Sea. Since 2011, blooms were regularly observed in warmer water, further south. Their developments in Central Atlantic are associated with mass strandings on the coasts, causing important damages and potentially dispersion of new bacteria. Microbiomes associated with pelagic Sargassum were analysed at large scale in Central Atlantic and near Caribbean Islands with a focus on pathogenic bacteria. Vibrio appeared widely distributed among pelagic Sargassum microbiome of our samples with higher occurrence than previously found in Mexico Gulf. Six out the 16 Vibrio-OTUs (Operational Taxonomic Unit), representing 81.2 ± 13.1% of the sequences, felt in cluster containing pathogens. Among the four different microbial profiles of pelagic Sargassum microbiome, Vibrio attained about 2% in two profiles whereas it peaked, in the two others, at 6.5 and 26.8% respectively, largely above the concentrations found in seawater surrounding raft (0.5%). In addition to sampling and measurements, we performed backward Lagrangian modelling of trajectories of rafts, and rebuilt the sampled rafts environmental history allowing us to estimate Sargassum growth rates along raft displacements. We found that Vibrio was favoured by high Sargassum growth rate and in situ ammonium and nitrite, modelled phosphate and nitrate concentrations, whereas zooplankters, benthic copepods, and calm wind (proxy of raft buoyancy near the sea surface) were less favourable for them. Relations between Vibrio and other main bacterial groups identified a competition with Alteromonas. According to forward Lagrangian tracking, part of rafts containing Vibrio could strand on the Caribbean coasts, however the strong decreases of modelled Sargassum growth rates along this displacement suggest unfavourable environment for Vibrio. For the conditions and areas observed, the sanitary risk seemed in consequence minor, but in other areas or conditions where high Sargassum growth rate occurred near coasts, it could be more important.
Assuntos
Microbiota , Sargassum , Vibrio , Animais , Região do Caribe , México , Água do Mar , Índias OcidentaisRESUMO
Alzheimer's disease (AD) is characterized by abnormal accumulation of extracellular amyloid beta protein (Aß) plaques and intracellular neurofibrillary tangles, as well as by a state of chronic inflammation in the central nervous system (CNS). Adverse activation of microglia, the brain immune cells, is believed to contribute to AD pathology including excessive neuronal death. Thus, normalizing immune functions of microglia could slow neurodegeneration, and identification of novel compounds capable of modifying microglial functions is an important goal. Since kainic acid (KA) has been shown to modulate microglial morphology and immune functions, we synthesized six new KA analogs (KAAs) and tested their effects on select microglial functions by using three different cell types as microglia models. Four of the KAAs at low micromolar concentrations inhibited secretion of cytotoxins, monocyte chemoattractant protein (MCP)-1, reactive oxygen species and nitric oxide (NO) by immune-stimulated microglia-like cells. We hypothesize that the effects of the novel KAAs on microglia-like cells are not mediated by KA receptors since their biological activity was distinct from that of KA in all assays performed. A structural similarity search identified aldose reductase (AR) as a potential target for the novel KAAs. This hypothesis was supported by use of AR inhibitor zopolrestat, which abolished the inhibitory effects of two KAAs on microglial secretion of NO. Since the newly developed KAAs inhibited pro-inflammatory and cytotoxic functions of microglia, they should be further investigated for their potential beneficial effect on neuroinflammation and neurodegeneration in AD animal models.
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Ácido Caínico/análogos & derivados , Ácido Caínico/farmacologia , Microglia/efeitos dos fármacos , Benzotiazóis/farmacologia , Células HL-60 , Humanos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Óxido Nítrico/metabolismo , Ftalazinas/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
A comprehensive survey of kainic acid analogs that have been tested for their biological activity is presented. Specifically, this review (1) gathers and compares over 100 kainoids according to a relative activity scale, (2) exposes structural features required to optimize affinity for kainate receptors, and (3) suggests design rules to create next-generation KA analogs. Literature SAR data are analyzed systematically and combined with the most recent crystallographic studies. In view of the renewed interest in neuroactive molecules, this review aims to help guide the efforts of organic synthesis laboratories, as well as to inform newcomers to KA/GluK research.