Recent advances in understanding the molecular basis of taste physiology in fish could open new opportunities to optimize feeding performance in aquaculture. This is particularly relevant at a time ...when alternative ingredients are being increasingly used, often reducing the digestibility and acceptability of fish diets, even if they are nutritionally balanced. The molecular characterization of fish taste receptors T1Rs and T2Rs revealed common taste discrimination mechanisms among vertebrates. In addition, data so far appear to indicate that taste signaling elements are conserved from fish to mammals. Nevertheless, fundamental differences between ligand specificities of taste receptors, and the presence of multiple T1R2s in fish species, underlines evolutionary adaptations of the T1R2 receptor to sense metabolically important nutrients, with a shift from sugars in mammals to amino acids in teleosts. This fits well with electrophysiological and behavioral studies on ligand specificities and taste preferences in several fish species. On the other hand, synergistic responses between different attractants could result from additive effects of independent receptor sites and response mechanisms, and this knowledge can be of practical interest to specifically design stimulant mixtures to modulate feed intake in aquaculture. Mammalian taste receptors and signaling elements have also been identified in the gastrointestinal tract, where they trigger multiple endocrine and neuronal pathways regulating digestion, nutrient absorption, feeding, and metabolism. Evidence for the existence of these receptors and signaling pathways in fish guts have recently been uncovered, suggesting that sensory properties of the diet might also have functional effects beyond oral taste sensations and palatability.
This study aimed to characterize amino acid sensing systems in the gastrointestinal tract (GIT) of the carnivorous fish model species rainbow trout. We observed that the trout GIT expresses mRNAs ...encoding some amino acid receptors described in mammals calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), and taste receptors type 1 members 1 and 2 (T1r1, T1r2), while others taste receptor type 1 member 3 (T1r3) and metabotropic glutamate receptors 1 and 4 (mGlur1, mGlur4) could not be found. Then, we characterized the response of such receptors, as well as that of intracellular signaling mechanisms, to the intragastric administration of L-leucine, L-valine, L-proline or L-glutamate. Results demonstrated that casr, gprc6a, tas1r1 and tas1r2 mRNAs are modulated by amino acids in the stomach and proximal intestine, with important differences with respect to mammals. Likewise, gut amino acid receptors triggered signaling pathways likely mediated, at least partly, by phospholipase C β3 and β4. Finally, the luminal presence of amino acids led to important changes in ghrelin, cholecystokinin, peptide YY and proglucagon mRNAs and/or protein levels. Present results offer the first set of evidence in favor of the existence of amino acid sensing mechanisms within the fish GIT.
Theobromine is a caffeine metabolite most abundant in dark chocolate, of which consumption is linked with a lower risk of cognitive decline. However, the mechanisms through which theobromine affects ...neuronal function remain ill-defined. Using electrophysiological recordings in mouse hippocampal synapses, we now characterized the impact of a realistic concentration of theobromine on synaptic transmission and plasticity. Theobromine (30 μM) facilitated synaptic transmission while decreasing the magnitude of long-term potentiation (LTP), with both effects being blunted by adenosine deaminase (2 U/mL). The pharmacological blockade of A1R with DPCPX (100 nM) eliminated the theobromine-dependent facilitation of synaptic transmission, whereas the A2AR antagonist SCH58261 (50 nM), as well as the genetic deletion of A2AR, abrogated the theobromine-induced impairment of LTP. Furthermore, theobromine prevented LTP deficits and neuronal loss, respectively, in mouse hippocampal slices and neuronal cultures exposed to Aβ1–42 peptides, considered a culprit of Alzheimer’s disease. Overall, these results indicate that theobromine affects information flow via the antagonism of adenosine receptors, normalizing synaptic plasticity and affording neuroprotection in dementia-related conditions in a manner similar to caffeine.
Mapping the Structure of Semantic Memory Morais, Ana Sofia; Olsson, Henrik; Schooler, Lael J.
Cognitive science,
January/February 2013, Letnik:
37, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Aggregating snippets from the semantic memories of many individuals may not yield a good map of an individual’s semantic memory. The authors analyze the structure of semantic networks that they ...sampled from individuals through a new snowball sampling paradigm during approximately 6 weeks of 1‐hr daily sessions. The semantic networks of individuals have a small‐world structure with short distances between words and high clustering. The distribution of links follows a power law truncated by an exponential cutoff, meaning that most words are poorly connected and a minority of words has a high, although bounded, number of connections. Existing aggregate networks mirror the individual link distributions, and so they are not scale‐free, as has been previously assumed; still, there are properties of individual structure that the aggregate networks do not reflect. A simulation of the new sampling process suggests that it can uncover the true structure of an individual’s semantic memory.
During development, neural circuit formation requires the stabilization of active γ-aminobutyric acid–mediated (GABAergic) synapses and the elimination of inactive ones. Here, we demonstrate that, ...although the activation of postsynaptic GABA type A receptors (GABA
Rs) and adenosine A
receptors (A
Rs) stabilizes GABAergic synapses, only A
R activation is sufficient. Both GABA
R- and A
R-dependent signaling pathways act synergistically to produce adenosine 3′,5′-monophosphate through the recruitment of the calcium–calmodulin–adenylyl cyclase pathway. Protein kinase A, thus activated, phosphorylates gephyrin on serine residue 303, which is required for GABA
R stabilization. Finally, the stabilization of pre- and postsynaptic GABAergic elements involves the interaction between gephyrin and the synaptogenic membrane protein Slitrk3. We propose that A
Rs act as detectors of active GABAergic synapses releasing GABA, adenosine triphosphate, and adenosine to regulate their fate toward stabilization or elimination.
Endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which are key events in the initiation and/or progression of several diseases, are correlated with alterations at ER-mitochondria ...contact sites, the so-called "Mitochondria-Associated Membranes" (MAMs). These intracellular structures are also implicated in NLRP3 inflammasome activation which is an important driver of sterile inflammation, however, the underlying molecular basis remains unclear. This work aimed to investigate the role of ER-mitochondria communication during ER stress-induced NLRP3 inflammasome activation in both peripheral and central innate immune systems, by using THP-1 human monocytes and BV2 microglia cells, respectively, as in vitro models. Markers of ER stress, mitochondrial dynamics and mass, as well as NLRP3 inflammasome activation were evaluated by Western Blot, IL-1β secretion was measured by ELISA, and ER-mitochondria contacts were quantified by transmission electron microscopy. Mitochondrial Ca
2+
uptake and polarization were analyzed with fluorescent probes, and measurement of aconitase and SOD2 activities monitored mitochondrial ROS accumulation. ER stress was demonstrated to activate the NLRP3 inflammasome in both peripheral and central immune cells. Studies in monocytes indicate that ER stress-induced NLRP3 inflammasome activation occurs by a Ca
2+
-dependent and ROS-independent mechanism, which is coupled with upregulation of MAMs-resident chaperones, closer ER-mitochondria contacts, as well as mitochondrial depolarization and impaired dynamics. Moreover, enhanced ER stress-induced NLRP3 inflammasome activation in the immune system was found associated with pathological conditions since it was observed in monocytes derived from bipolar disorder (BD) patients, supporting a pro-inflammatory status in BD. In conclusion, by demonstrating that ER-mitochondria communication plays a key role in the response of the innate immune cells to ER stress, this work contributes to elucidate the molecular mechanisms underlying NLRP3 inflammasome activation under stress conditions, and to disclose novel potential therapeutic targets for diseases associated with sterile inflammation.
Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases ...and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature recorded a significantly increased feed intake, these results clearly suggested that at high, sub-optimal water temperature, fish metabolism attempted to increment its overall ARA status -the most bioactive LC-PUFA participating in the inflammatory response- by modulating the metabolic fate of dietary ARA (expressed as % of net intake), reducing its β-oxidation and favouring synthesis and deposition. This correlates also with results from other recent studies showing that both immune- and stress- responses in fish are up regulated in fish held at high temperatures. This is a novel and fundamental information that warrants industry and scientific attention, in consideration of the imminent increase in water temperatures, continuous expansion of aquaculture operations, resources utilisation in aquafeed and much needed seasonal/adaptive nutritional strategies.
The present study presents the first “in vivo” evidence of enzymatic activity and nutritional regulation of a Δ4-desaturase-dependent DHA synthesis pathway in the teleost Solea senegalensis. Juvenile ...fish were fed diets containing 2 lipid levels (8 and 18%, LL and HL) with either 100% fish oil (FO) or 75% of the FO replaced by vegetable oils (VOs). Fatty acyl elongation (Elovl5) and desaturation (Δ4Fad) activities were measured in isolated enterocytes and hepatocytes incubated with radiolabeled α-linolenic acid (ALA; 18:3n−3) and eicosapentaenoic acid (EPA; 20:5n−3). Tissue distributions of elovl5 and Δ4fad transcripts were also determined, and the transcriptional regulation of these genes in liver and intestine was assessed at fasting and postprandially. DHA biosynthesis from EPA occurred in both cell types, although Elovl5 and Δ4Fad activities tended to be higher in hepatocytes. In contrast, no Δ6Fad activity was detected on 14C-ALA, which was only elongated to 20:3n−3. Enzymatic activities and gene transcription were modulated by dietary lipid level (LL>HL) and fatty acid (FA) composition (VO>FO), more significantly in the liver than in the intestine, which was reflected in tissue FA compositions. Dietary VO induced a significant up-regulation of Δ4fad transcripts in the liver 6h after feeding, whereas in fasting conditions the effect of lipid level possibly prevailed over or interacted with FA composition in regulating the expression of elovl5 and Δ4fad, which were down-regulated in the liver of fish fed the HL diets. Results indicated functionality and biological relevance of the Δ4 LC-PUFA biosynthesis pathway in S. senegalensis.
•We present the first “in vivo” evidence of a Δ4Fad dependent DHA synthesis pathway.•No Δ6Fad activity was found.•DHA biosynthesis from EPA occurred in hepatocytes and enterocytes.•The pathway is modulated by dietary lipid level and fatty acid composition.•We highlight high plasticity and functional variability of the pathway in teleosts.
Objectives: To compare the bond strength of printed and conventionally produced denture base resins to reline resins after being submitted to a physical-chemical aging process. Methods: Sixty ...specimens (10×10×3.3 mm) of two printed (V-Print Dentbase and Denture 3D+) and one conventionally produced (Probase Hot) denture base resins were relined with two acrylic resins: Ufi Gel Hard C and Probase Cold (n=10). The specimens were submitted to 1000 cycles of thermal fluctuations (5-55ºC) and 28 days of pH cycles using pH=3 (8 h/day) and pH=7 (16 h/day). Then, the shear bond strength was evaluated (1 KN; 1 mm/min), and the failure mode was classified as adhesive, cohesive, or mixed type. Data were analyzed with Kruskal-Wallis and t-tests (=0.05). Results: Bond strength values ranged from 8.9 to 21.5 MPa. No statistically significant (p=0.07) differences were found between the bond strength of the three denture base acrylic resins. The reline resin did not significantly (p=0.07) affect the bond strength of the two printed resins. However, relining the Probase Hot with Probase Cold yielded a higher bond strength (p<0.001) than with Ufi Gel Hard C. Only the Probase Hot-Ufi Gel Hard C group revealed 100% of failures classified as adhesive type. Conclusions: The two printed denture base resins obtained similar bond strength to conventionally produced denture base resin after being submitted to thermal and chemical aging
Introdução: As perturbações do neurodesenvolvimento são caracterizadas pelo atraso ou alteração na aquisição de capacidades em vários domínios do desenvolvimento: motor, social, de linguagem e ...cognitivo. Deste modo, estas perturbações podem manifestar-se desde a infância até à vida adulta, exigindo a continuidade dos cuidados de saúde. Contudo, vários estudos mostram que existem limitações de acesso dos adultos aos cuidados de saúde nesta área clínica.Métodos: Foi realizado um estudo observacional descritivo transversal através da aplicação de um questionário anónimo a médicos de Psiquiatria, a nível nacional, no período compreendido entre 6 de outubro e 6 de dezembro de 2020.Resultados: Foram recolhidos dados de 83 médicos de Psiquiatria (43 internos de especialidade e 40 especialistas). A nível nacional, apenas 16,9% dos serviços de Psiquiatria tinham uma consulta diferenciada de neurodesenvolvimento. Os médicos respondentes reportaram ter observado poucos doentes com perturbações do neurodesenvolvimento: 72,3% observaram um ou nenhum por semana. Dos médicos que referiram ter consulta de neurodesenvolvimento no seu serviço, a maioria (64,3%) não dispunha de equipa multidisciplinar. A transição destes doentes da consulta de Pediatria do Neurodesenvolvimento/Pedopsiquiatria para a de Psiquiatria ocorria em 51,8% por transferência regular intra-hospitalar, contudo em apenas 15,7% ocorria através de protocolo específico ou com a realização de consulta de transição. Por fim, 88% dos médicos de Psiquiatria consideraram ser pertinente a existência de uma consulta de perturbações do neurodesenvolvimento no adulto e relataram não possuir formação especializada na área do neurodesenvolvimento.Conclusão: Este estudo possibilitou enumerar alguns obstáculos para que os doentes com perturbações do neurodesenvolvimento usufruam de uma transição de cuidados de saúde para a vida adulta favorável: carência de conhecimento na área, necessidade de melhor comunicação entre serviços, falta de protocolos específicos, escassez de equipas multidisciplinares e assimetria na distribuição de cuidados de saúde diferenciados.
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