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Histological and biochemical studies elucidated the protective mechanism adopted by four species of Polybranchioidea molluscs of ascoglossan species to prevent predation. Normal and regenerated dorso-lateral appendages, called cerata, present in the species Cyerce cristallina and Ercolania funerea, facilitated autotomic processes. Caliphylla mediterranea and Placida dendritica do not exhibit autotomic processess and avail themselves of large quantities of chloroplasts which function as camouflaging materials. This enables the species to escape predation.

In a previous work, we have presented an innovative theoretical model to describe the evolution of the life cycle of a new technology. We have proposed a mathematical approach based on a rate equation, similar to that used to describe quantum level transitions. The model is able to describe the hype curve evolution in many relevant conditions, which can be associated with various external parameters. In this article, we apply this model to describe the evolution of the number of publications in some different research fields that are very current and extremely advanced in terms of social impact. The applications have been chosen in the fields of biomolecular chemistry, genetics and superconducting nanoelectronics. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than Δ(9) -tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival.Experimental Approach: We tested pure cannabinoids and extracts from Cannabis strains enriched in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU-145 cells.Key Results: Cannabidiol (CBD) significantly inhibited cell viability. Other compounds became effective in cells deprived of serum for 24 h. Several BDS were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca(2+)). In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis.Conclusions and Implications: These data support the clinical testing of CBD against prostate carcinoma. [ABSTRACT FROM AUTHOR]

Background and Purpose: Two oxidation products of linoleic acid, 9- and 13-hydroxy-octadecadienoic acids (HODEs), have recently been suggested to act as endovanilloids, that is, endogenous agonists of transient receptor potential vanilloid-1 (TRPV1) channels, thereby contributing to inflammatory hyperalgesia in rats. However, HODE activity at rat TRPV1 in comparison with the best established endovanilloid, anandamide, and its enantioselectivity and selectivity towards other TRP channels that are also abundant in sensory neurons have never been investigated.Experimental Approach: We studied the effect of 9(R)-HODE, 9(S)-HODE, (+/-)13-HODE, 15(S)-hydroxyanandamide and anandamide on [Ca(2+) ](i) in HEK-293 cells stably expressing the rat or human recombinant TRPV1, or rat recombinant TRPV2, TRPA1 or TRPM8, and also the effect of 9(S)-HODE in rat dorsal root ganglion (DRG) neurons by calcium imaging.Key Results: Anandamide and 15(S)-hydroxyanandamide were the most potent endovanilloids at human TRPV1, whereas 9(S)-HODE was approximately threefold less efficacious and 75- and 3-fold less potent, respectively, and did not perform much better at rat TRPV1. The 9(R)-HODE and (+/-)13-HODE were almost inactive at TRPV1. Unlike anandamide and 15(S)-hydroxyanandamide, all HODEs were very weak at desensitizing TRPV1 to the action of capsaicin, but activated rat TRPV2 [only (+/-)13-HODE] and rat TRPA1, and antagonized rat TRPM8, at concentrations higher than those required to activate TRPV1. Finally, 9(S)-HODE elevated [Ca(2+) ](i) in DRG neurons almost exclusively in capsaicin-sensitive cells but only at concentrations between 25 and 100 μM.Conclusions and Implications: The present data suggest that HODEs are less important endovanilloids than anandamide.Linked Articles: This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8. [ABSTRACT FROM AUTHOR]

Background and Purpose: Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.Experimental Approach: Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC-induced elevation of intracellular Ca(2+) [Ca(2+)](i) was assessed in HEK293 cells transfected with rat TRPA1 channels.Key Results: AITC increased [Ca(2+)](i) in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS-induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC-030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects in HEK293 cells but not in the ileum or colon. AITC-induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC-030031.Conclusion and Implications: AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised. [ABSTRACT FROM AUTHOR]

The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. Thus, we hypothesized that umbellulone stimulates the transient receptor potential ankyrin 1 channel in a subset of peptidergic, nocioceptive neurons, activating the trigeminovascular system via this mechanism. Umbellulone, from µM to sub-mM concentrations, selectively stimulated transient receptor potential ankyrin 1-expressing HEK293 cells and rat trigeminal ganglion neurons, but not untransfected cells or neurons in the presence of the selective transient receptor potential ankyrin 1 antagonist, HC-030031. Umbellulone evoked a calcium-dependent release of calcitonin gene-related peptide from rodent trigeminal nerve terminals in the dura mater. In wild-type mice, umbellulone elicited excitation of trigeminal neurons and released calcitonin gene-related peptide from sensory nerve terminals. These two responses were absent in transient receptor potential ankyrin 1 deficient mice. Umbellulone caused nocioceptive behaviour after stimulation of trigeminal nerve terminals in wild-type, but not transient receptor potential ankyrin 1 deficient mice. Intranasal application or intravenous injection of umbellulone increased rat meningeal blood flow in a dose-dependent manner; a response selectively inhibited by systemic administration of transient receptor potential ankyrin 1 or calcitonin gene-related peptide receptor antagonists. These data indicate that umbellulone activates, through a transient receptor potential ankyrin 1-dependent mechanism, the trigeminovascular system, thereby causing nocioceptive responses and calcitonin gene-related peptide release. Pharmacokinetics of umbellulone, given by either intravenous or intranasal administration, suggest that transient receptor potential ankyrin 1 stimulation, which eventually results in meningeal vasodilatation, may be produced via two different pathways, depending on the dose. Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain. [ABSTRACT FROM AUTHOR]

Objective: Preparation and characterization of anandamide (N-arachidonoyl-ethanolamine, AEA) loaded polycaprolactone nanoparticles (PCL NP) as a research tool to clarify the presence of an AEA transporter in cell membranes and to avoid AEA plastic adsorption and instability. Materials and methods: High performance liquid chromatography and light scattering were used to determine encapsulation efficiency, particle size, drug release, permeability and stability. Results: A high encapsulation efficiency 96.05 ±± 1.77%% and a particle size of 83.52 ±± 21.38 nm were obtained. Nearly 40%% of AEA remained in the NP after a 99.9%% dilution and only 50%% was released after 24 h at 37°°C with a 99%% dilution. PCL NP prevented the adsorption of the drug to polypropylene or polystyrene, but not to acrylic multiwell plates. Drug permeability through artificial membranes was low (10−−7 to 10−−8 cm/s) and was affected by the presence of NP. NP increased AEA stability in suspension (drug half-life 431 h vs. 12 h) and freeze-dried with 5%% sucrose. Conclusion: This article presents the first study where stable AEA-loaded NP with high encapsulation efficiencies have been obtained. [ABSTRACT FROM AUTHOR]

Highly fluorescent Au/polystyrene nanocomposite films have been prepared by thermal decomposition at 250°C of gold mercaptide molecules (dodecyl-mercaptide of gold(I), C12H25SAu) dissolved in polystyrene. Owing to a continuous nucleation of metallic phase generated by the thermolysis reaction, molecular gold clusters, which are characterized by fluorescence properties because of the very small size, can be obtained by this very simple technique. [ABSTRACT FROM AUTHOR]

Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and dorsal root ganglia. In this study, we over-expressed both receptor types in human embryonic kidney (HEK)-293 cells and investigated the effect of the CB1 agonist HU-210 on the VR1-mediated increase in intracellular Ca2+ ([Ca2+]i), a well-known response of the prototypical VR1 agonist capsaicin. After a 5-min pre-treatment, HU-210 (0.1 μM) significantly enhanced the effect of several concentrations of capsaicin on [Ca2+]i in HEK-293 cells over-expressing both rat CB1 and human VR1 (CB1-VR1-HEK cells), but not in cells over-expressing only human VR1 (VR1-HEK cells). This effect was blocked by the CB1 receptor antagonist SR141716A (0.5 μM), and by phosphoinositide-3-kinase and phospholipase C inhibitors. The endogenous agonist of CB1 and VR1 receptors, anandamide, was more efficacious in inducing a VR1-mediated stimulation of [Ca2+]i in CB1-VR1-HEK cells than in VR1-HEK cells, and part of its effect on the former cells was blocked by SR141716A (0.5 μM). Pre-treatment of CB1-VR1-HEK cells with forskolin, an adenylate cyclase activator, enhanced the capsaicin effect on [Ca2+]i. HU-210, which in the same cells inhibits forskolin-induced enhancement of cAMP levels, blocked the stimulatory effect of forskolin on capsaicin. Our data suggest that in cells co-expressing both CB1 and VR1 receptors, pre-treatment with CB1 agonists inhibits or stimulates VR1 gating by capsaicin depending on whether or not cAMP-mediated signalling has been concomitantly activated. [ABSTRACT FROM AUTHOR]

The endogenous cannabinoid receptor ligand, anandamide (AEA), is a full agonist of the vanilloid receptor type 1 (VR1) for capsaicin. Here, we demonstrate that the potency and efficacy of AEA at VR1 receptors can be significantly increased by the concomitant activation of protein kinase A (PKA). In human embryonic kidney (HEK) cells over-expressing human VR1, AEA induces a rise in cytosolic Ca[sup 2+] concentration that is mediated by this receptor. The EC[sub 50] for this effect was decreased five-fold in the presence of forskolin (FRSK, 1–5 µm) or the cAMP analogue, 8-Br-cAMP (10–100 µm). The effects of 8-Br-cAMP and FRSK were blocked by a selective PKA inhibitor. The FRSK (10 nm) also potently enhanced the sensory neurone- and VR1-mediated constriction by AEA of isolated guinea-pig bronchi, and this effect was abolished by a PKA inhibitor. In rat dorsal root ganglia slices, AEA-induced release of substance P, an effect mediated by VR1 activation, was enhanced three-fold by FRSK (10 nm). Thus, the ability of AEA to stimulate sensory VR1, with subsequent neuropeptide release, appears to be regulated by the state of activation of PKA. This observation supports the hypothesis that endogenous AEA might stimulate VR1 under certain pathophysiological conditions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We have recently reported the occurrence of 9( R)-hydroxy-, 9( R)-hydroperoxy- and 9-keto-octadeca-10 E,12 Z,15 Z-trienoic acids (9-HOTrE, 9-HPOTrE and 9-KOTrE) in Hydra vulgaris, and their biosynthesis from α-linolenic acid (α-LA) through the action of an enantioselective ω 10( R)-lipoxygenase (ω10-LO). Here we describe the finding of these α-LA metabolites as esters to the 2-position of phosphatidylcholine, phosphatidylethanolamine and, in trace amounts, phosphatidylinositol. Small amounts of a compound co-eluting with an authentic standard of 9( R)-hydroxy-octadeca-10 E,12 Z-dienoic acid, a metabolite potentially derived from the action of ω 10-LO on linoleic acid, were also found esterified with phospholipids. Since direct peroxidation of membrane lipids has been described, experiments were aimed at establishing whether α-LA metabolite-containing phospholipids could originate, in H. vulgaris, from either spontaneous or ω 10-LO-catalyzed oxidation of phospholipid-bound α-LA. Incubation of either unlabelled or radiolabelled PUFA-containing phosphoglycerides with H. vulgaris ω 10-LO did not result in their peroxidation. This suggests that α-LA and LA metabolites are incorporated into glycerophospholipids after their formation by ω 10-LO, and that, as in mamals, membrane phospholipids may serve as a reservoir for these bioactive compounds. This is the first example in an invertebrate species of lipoxygenase products esterified to phosphoglycerides. [ABSTRACT FROM AUTHOR]

The participation of protein kinase C (PKC) in the regeneration of tentacles of Hydra vulgaris was studied. Regeneration was induced by 1,2- sn-dioctanoyl-glycerol (diC) and the novel diterpenoidic diacylglycerol verrucosin B (VB), a potent PKC activator extracted from marine sources. VB substantially increased Hydra average tentacle number (ATN) at concentrations 10,000 times lower than those needed for diC to exert an analogous effect. When both synthetic and natural VB analogues were tested, the structure/activity relationship found in Hydra tentacle regeneration was identical to that known for DAG-induced activation of PKC in vitro. VB-induced increase of ATN was strongly counteracted by the PKC inhibitors sphingosine and A3, but was not synergic with a tenfold increase of extracellular Ca concentration or with an increase of intracellular Ca concentration obtained either with the ionophore A23187 or with thapsigargin. This suggested the involvement of a non-Ca-dependent PKC in VB-triggered Hydra tentacle regeneration. The involvement of phospholipase A (PLA) activation in Hydra regenerative processes was studied using the novel site-specific inhibitor of the enzyme, oleyloxyethylphosphorylcholine (OOPC), which brought about a striking inhibition of ATN in the low μmolar range. This effect was reversed by arachidonic acid (AA), while an enhancement of ATN was also observed with an inhibitor of AA uptake from membrane phospholipids, thus suggesting that PLA-catalysed liberation of AA is involved in Hydra tentacle regeneration. OOPC also blocked verrucosin B-induced PKC-mediated enhancement of ATN, thus suggesting that this effect is also mediated by PLA activation. ATN was increased also by compound 48/80, a direct activator of pertussis toxin-sensitive GTP-binding proteins, and this effect was counteracted by pertussis toxin pretreatment. None of the known AA cascade inhibitors exhibited an effect on ATN comparable to that exerted by OOPC, but, surprisingly, the cycloxygenase inhibitor indomethacin strongly enhanced ATN, thus suggesting that prostanoids might effect a negative control on Hydra regenerative processes. This represents the first attempt so far reported to study the implication of more than one biochemical pathway as a signalling event in the hydroid regenerative processes. [ABSTRACT FROM AUTHOR]

The extraordinary regenerative phenomena in the marine ascoglossan mollusc Cyerce cristallina are described here for the first time. The possible correlation between cyercenes, pyrones recently isolated from the mollusc regenerating dorsal appendages (cerata), and the processes of chemical defense and regeneration in the mollusc, was investigated by studying the tissue distribution, biological activity and biogenesis of cyercenes. Differences in distribution between the C. cristallina mantle, cerata and mucous secretion were found. Cyercenes showed activity in the Hydra vulgaris regeneration assay and the mosquito fish ichthyotoxicity assay. The de novo biosynthesis of cyercenes from propionic acid was demonstrated by means of in vivo adsorption experiments with radiolabeled propionate. [ABSTRACT FROM AUTHOR]

Aberrations and the distortions due to the imaging optics can be compensated in quantitative phase microscopy of thin phase objects by digital holography using a single hologram. The reconstructed quantitative phase microscopy phase distribution map can be directly corrected in the reconstructed image plane by a numerical method. To remove this unwanted aberration, in the special case of thin objects, the authors perform a two-dimensional fit with the Zernike polynomials of the reconstructed unwrapped phase. Subtraction of the fitted polynomial from the original phase map gives quantitative phase microscopy phase map free of aberrations. [ABSTRACT FROM AUTHOR]

Highlights: [•] Sixteen derivatives of perillaketone has been designed and synthesised. [•] Their potency, efficacy and desensibilisation activity have been measured (in vitro on rTRPA1). [•] Most derivatives proved to be high potency agonists of TRPA1. [•] Their potency is higher than most natural agonists reported in the literature. [•] These furylketones derivatives represent a new class of compounds active on TRPA1. [Copyright &y& Elsevier]