Dopamine D2 receptor signaling via the arachidonic acid cascade: modulation by cAMP-dependent protein kinase A and prostaglandin E2

Recent studies have shown that, in Chinese hamster ovary cells transfected with D2-receptor cDNA, CHO(D2) cells, D2 agonists are potent in enhancing the release of [3H]arachidonic acid (AA) induced by stimulation of constitutive purinergic receptors or by application of Ca2+ ionophores. This facilitatory action is further amplified by the concomitant activation of D1 receptors, which per se have no effect on evoked [3H]AA release. Here, we review a series of experiments aimed at examining the molecular mechanism of this synergistic interaction. The results show that, in CHO(D2) cells: (a) application of 8-Br-cAMP or stimulation of constitutive prostaglandin (PG)E2 receptors augment the AA response produced by D2 agonists; (b) in CHO(D2) cells transfected with human beta 2-receptor cDNA, the beta-agonist, isoproterenol, produces a similar effect; (c) the potentiation of [3H]AA release produced by PGE2 and 8-Br-cAMP is prevented by overexpressing either a protein inhibitor of cAMP-dependent protein kinase (PKA) or a mutated form of pKA regulatory subunit incapable of binding cAMP; (d) mock-synergism is obtained in CHO(D2) cells overexpressing the catalytic subunit of PKA; (e) PGE2 is a major AA metabolite in stimulated CHO(D2) cells and its formation may contribute to the effect of D2 agonists on AA release. The results indicate that cAMP-induced activation of PKA represents a likely molecular basis for D1/D2 receptor synergism on AA release. They also suggest that additional membrane receptors, colocalized with D2 and positively linked to adenylyl cyclase, may exert a similar action. Furthermore, stimulation of PGE2 receptors by endogenously produced prostaglandin may participate in AA signaling at the D2 receptor, by providing a paracrine positive feedback loop.     

Novel diterpenoid diacylglycerols from marine molluscs: potent morphogens and protein kinase C activators

Five novel 1,2-sn-diacylglycerols with diterpenoid acyl moieties in the sn-1 position were isolated and characterized, together with the corresponding 1,3-sn-diacylglycerols, from three species of dorid nudibranchs molluscs. Their potent activity as morphogens in vivo in the Hydra tentacle regeneration assay and their parallel activity as activators of rat brain protein kinase C (PKC) in vitro are reported here. Our findings promote the use of these compounds as useful molecular probes for both in vivo and in vitro studies on the participation of PKC in cell development.     

Maximum Likelihood Sound Source Localization and Beamforming for Directional Microphone Arrays in Distributed Meetings

In distributed meeting applications, microphone arrays have been widely used to capture superior speech sound and perform speaker localization through sound source localization (SSL) and beamforming. This paper presents a unified maximum likelihood framework of these two techniques, and demonstrates how such a framework can be adapted to create efficient SSL and beamforming algorithms for reverberant rooms and unknown directional patterns of microphones. The proposed method is closely related to steered response power-based algorithms, which are known to work extremely well in real-world environments. We demonstrate the effectiveness of the proposed method on challenging synthetic and real-world datasets, including over six hours of recorded meetings.     

Description and composition of bio-inspired design patterns: a complete overview

In the last decade, bio-inspired self-organising mechanisms have been applied to different domains, achieving results beyond traditional approaches. However, researchers usually use these mechanisms in an ad-hoc manner. In this way, their interpretation, definition, boundary (i.e. when one mechanism stops, and when another starts), and implementation typically vary in the existing literature, thus preventing these mechanisms from being applied clearly and systematically to solve recurrent problems. To ease engineering of artificial bio-inspired systems, this paper describes a catalogue of bio-inspired mechanisms in terms of modular and reusable design patterns organised into different layers. This catalogue uniformly frames and classifies a variety of different patterns. Additionally, this paper places the design patterns inside existing self-organising methodologies and hints for selecting and using a design pattern.     

Analogues of perillaketone as highly potent agonists of TRPA1 channel

Transient receptor potential (TRP) channels represent interesting molecular target structures involved in a number of different physiological and pathophysiological systems. In particular, TRPA1 channel is involved in nociception and in sensory perception of many pungent chemesthetic compounds, which are widespread in spices and food plants, including Perilla frutescens. A natural compound from P. frutescens (isoegomaketone) and 16 synthetic derivatives of perillaketone have been prepared and tested in vitro on rTRPA1 expressed in HEK293 cells and their potency, efficacy and desensibilisation activity measured. Most derivatives proved to be high potency agonists of TRPA1, with a potency higher than most natural agonists reported in the literature. These furylketones derivatives, represent a new class of chemical structures active on TRPA1 with many potential applications in the agrifood and pharmaceutical industry.     

Dietary krill oil increases docosahexaenoic acid and reduces 2-arachidonoylglycerol but not N-acylethanolamine levels in the brain of obese Zucker rats

Evidence suggests that dietary long chain polyunsaturated fatty acids (LCPUFAs), and particularly those belonging to the n-3 family, may influence the brain fatty acid profile and, thereby, the biosynthesis of endocannabinoids in rodents. However, the doses used are usually quite high and not comparable with human intake. Recently, we have shown that relatively low doses of dietary n-3 LCPUFAs (4 weeks), in the form of either fish or krill oil, balanced for EPA and DHA content, and against a control diet with no EPA and DHA and similar contents of oleic, linoleic and α-linolenic acids, lower the concentrations of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in the visceral adipose tissue, and of AEA in the liver and heart, of obese Zucker rats. This, in turn, is associated with lower levels of arachidonic acid in membrane phospholipids and with amelioration of some metabolic syndrome parameters. We investigated here whether in Zucker rats, under the same conditions, fish and krill oil are also able to influence LCPUFA and endocannabinoid profiles in brain. Only krill oil was able to increase significantly DHA levels in brain phospholipids, with no changes in arachidonic acid. DHA increase was associated with lower levels of 2-AG in the brain, whereas AEA and its congeners, N-palmitoylethanolamine and N-oleoylethanolamine, were unchanged. We conclude that, despite the strong impact of dietary n-3 fatty acid on endocannabinoid levels previously observed in peripheral tissues, in the brain only 2-AG is affected by dietary krill oil, suggesting that the beneficial effect of the latter on the metabolic syndrome is mostly exerted by modifying peripheral endocannabinoids. Nevertheless, possible effects of dietary krill oil in the brain through modification of 2-AG levels deserve further investigation.     

Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action

The existence of an endogenous cannabinoid system was demonstrated conclusively with the discovery of endogenous brain constituents capable of activating the cannabinoid receptors functionally. These compounds are synthesized by neuronal cells and inactivated through re-uptake and enzymatic hydrolysis by both neurons and astrocytes. In analogy with the endorphins they can be referred to as endocannabinoids. Apart from the identification of their metabolic pathways, research carried out in the past six years has focused on the possible cellular and molecular targets for the actions of endocannabinoids. These studies have confirmed a similarity between the endocannabinoids and the psychoactive substance in marijuana, delta9(-)-tetrahydrocannabinol, and have suggested a role for endocannabinoids in the modulation of neurotransmitter action and release.     

Similarity of phylogenetic trees as indicator of protein-protein interaction

Deciphering the network of protein interactions that underlinescellular operations has become one of the main tasks of proteomicsand computational biology. Recently, a set of bioinformaticsapproaches has emerged for the prediction of possible interactionsby combining sequence and genomic information. Even though theinitial results are very promising, the current methods arestill far from perfect. We propose here a new way of discoveringpossible protein–protein interactions based on the comparisonof the evolutionary distances between the sequences of the associatedprotein families, an idea based on previous observations ofcorrespondence between the phylogenetic trees of associatedproteins in systems such as ligands and receptors. Here, weextend the approach to different test sets, including the statisticalevaluation of their capacity to predict protein interactions.To demonstrate the possibilities of the system to perform large-scalepredictions of interactions, we present the application to acollection of more than 67 000 pairs of E.coli proteins, ofwhich 2742 are predicted to correspond to interacting proteins.