Neurotrophins in Zebrafish Taste Buds

SIMPLE SUMMARY: Zebrafish is a powerful vertebrate model organism, whose similarities with mammals are fundamental to validate its use for experimental purposes. In this study, the authors demonstrate the presence of neurotrophic factors, namely neurotrophins, in numerous taste bud cells of this fish. The reported results suggest an essential role of these factors in taste bud function. Interestingly, the results described in this study are in accordance with those reported in some mammalian species. Therefore, despite the different anatomical characteristics of the anterior digestive tract in mammals and fish, the taste buds maintain similarities in both shape and functional mechanisms in the two classes. ABSTRACT: The neurotrophin family is composed of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), Neurotrophin 3 (NT3) and NT4. These neurotrophins regulate several crucial functions through the activation of two types of transmembrane receptors, namely p75, which binds all neurotrophins with a similar affinity, and tyrosine kinase (Trk) receptors. Neurotrophins, besides their well-known pivotal role in the development and maintenance of the nervous system, also display the ability to regulate the development of taste buds in mammals. Therefore, the aim of this study is to investigate if NGF, BDNF, NT3 and NT4 are also present in the taste buds of zebrafish (Danio rerio), a powerful vertebrate model organism. Morphological analyses carried out on adult zebrafish showed the presence of neurotrophins in taste bud cells of the oropharyngeal cavity, also suggesting that BDNF positive cells are the prevalent cell population in the posterior part of the oropharyngeal region. In conclusion, by suggesting that all tested neurotrophins are present in zebrafish sensory cells, our results lead to the assumption that taste bud cells in this fish species contain the same homologous neurotrophins reported in mammals, further confirming the high impact of the zebrafish model in translational research

An Alkaloid from a Highly Invasive Seaweed Increases the Voracity and Reproductive Output of a Model Fish Species

The invasive macroalga Caulerpa cylindracea has spread widely in the Mediterranean Sea, becoming a favorite food item for native fish for reasons yet unknown. By using a combination of behavioral, morphological, and molecular approaches, herein we provide evidence that the bisindole alkaloid caulerpin, a major secondary metabolite of C. cylindracea, significantly increases food intake in the model fish Danio rerio, influencing the regulation of genes involved in the orexigenic pathway. In addition, we found that the compound improves fish reproductive performance by affecting the hypothalamus-pituitary-gonadal axis. The obtained results pave the way for the possible valorization of C. cylindracea as a sustainable source of a functional feed additive of interest to face critical challenges both in aquaculture and in human nutrition

Inhibitory effect of positively charged triazine antagonists of prokinecitin receptors on the transient receptor vanilloid type-1 (TRPV1) channel

Four positively charged compounds, previously shown to produce analgesic activity by interacting with prokinecitin receptor or T-type calcium channels, were tested for their ability to inhibit capsaicin-induced elevation of intracellular Ca(2+) elevation in HEK-293 cells stably transfected with the human recombinant TRPV1, with the goal of identifying novel TRPV1 open-pore inhibitors. KYS-05090 showed the highest potency as a TRPV1 antagonist, even higher than that of the open-pore triazine 8aA inhibitor. The latter showed quite remarkable agonist/desensitizer activity at the rat recombinant TRPM8 channel. The activity of KYS-05090 and the other compounds was selective because none of these compounds was able to modulate the rat TRPA1 channel. Open-pore inhibitors of TRPV1 may be a new class of multi-target analgesics with lesser side effects, such as loss of acute pain sensitivity and hyperthermia, than most TRPV1 antagonists developed so far

Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid

Objective: To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). Methods: The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. Results: When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. Conclusions: These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs

Evolution of the business models for contemporary art galleries. Current situation and future challenges

Purpose – This paper aims at investigating the possible evolution of the business model of contemporary art galleries in the current international scenario. In the context of global crisis that has seriously affected cultural organizations, especially in Europe, the contemporary art market shows countertrend results. The art market, measured by auction results, has realized and is still realizing good and increasing performance, in terms of general sales and revenues. In particular, contemporary art represents a big business for auction operators, becoming one of the most profitable sectors in the art market. Despite this positive trend, contemporary art galleries are facing a difficult situation. With the exception of a handful of big galleries, many galleries generate only small profits and often they are compelled to close down their business. This apparently contradictory situation is strictly connected to the current business model of contemporary art galleries and underlines the need to rethink them in accordance with innovative ways of creation of social and economic value and fulfilment of a durable financial sustainability. Design/methodology/approach – The methodological approach combines the analysis of the literature with an empirical case study analysis. The goal is to explore the possibility of application of a successful business model in the field of contemporary art galleries. Consistently with this methodological approach, our paper is divided into three parts. In the first part we analyze the contemporary art market and the concept of business model in general, focusing on the current prevailing framework and the analysis of the literature on these subjects. In the second part we analyze a case of one of the most important Italian galleries: Galleria Continua. The in-depth examination of this case study leads to some evidence on the application of business strategy and management tools in the art galleries. More specifically the analysis of the business model of this art gallery is useful to identify a set of best practices . In the third and final part, in the light of what we have developed in the previous parts, we suggest some elements that could form the basis for innovation in the business model for contemporary art galleries. Originality/value – This paper aims at describing the present business model of contemporary art galleries and at proposing a new, sustainable one. In this sense, we think that this paper presents characteristics of originality. Moreover, another aspect of originality lies in the study of the role of an important reality of the cultural and creative sector, the contemporary art galleries. Especially in the Italian national context, the studies on contemporary art galleries are often considered secondary to those on "traditional" cultural organizations (like museums, theatres or heritage sites). Practical implications – The outcomes of the application are linked to the proposal of practical remarks for the evolution and development of business models for contemporary art galleries, as a new tool of creation of economic and social value in the cultural and creative sectors

Evolution of the business models for contemporary art galleries. Current situation and future challenges

Purpose – This paper aims at investigating the possible evolution of the business model of contemporary art galleries in the current international scenario. In the context of global crisis that has seriously affected cultural organizations, especially in Europe, the contemporary art market shows countertrend results. The art market, measured by auction results, has realized and is still realizing good and increasing performance, in terms of general sales and revenues. In particular, contemporary art represents a big business for auction operators, becoming one of the most profitable sectors in the art market. Despite this positive trend, contemporary art galleries are facing a difficult situation. With the exception of a handful of big galleries, many galleries generate only small profits and often they are compelled to close down their business. This apparently contradictory situation is strictly connected to the current business model of contemporary art galleries and underlines the need to rethink them in accordance with innovative ways of creation of social and economic value and fulfilment of a durable financial sustainability. Design/methodology/approach – The methodological approach combines the analysis of the literature with an empirical case study analysis. The goal is to explore the possibility of application of a successful business model in the field of contemporary art galleries. Consistently with this methodological approach, our paper is divided into three parts. In the first part we analyze the contemporary art market and the concept of business model in general, focusing on the current prevailing framework and the analysis of the literature on these subjects. In the second part we analyze a case of one of the most important Italian galleries: Galleria Continua. The in-depth examination of this case study leads to some evidence on the application of business strategy and management tools in the art galleries. More specifically the analysis of the business model of this art gallery is useful to identify a set of best practices . In the third and final part, in the light of what we have developed in the previous parts, we suggest some elements that could form the basis for innovation in the business model for contemporary art galleries. Originality/value – This paper aims at describing the present business model of contemporary art galleries and at proposing a new, sustainable one. In this sense, we think that this paper presents characteristics of originality. Moreover, another aspect of originality lies in the study of the role of an important reality of the cultural and creative sector, the contemporary art galleries. Especially in the Italian national context, the studies on contemporary art galleries are often considered secondary to those on "traditional" cultural organizations (like museums, theatres or heritage sites). Practical implications – The outcomes of the application are linked to the proposal of practical remarks for the evolution and development of business models for contemporary art galleries, as a new tool of creation of economic and social value in the cultural and creative sectors

Neurodegeneration in zebrafish embryos and adults after cadmium exposure

Cadmium is a biologically non-essential metal. It is also toxic to many organs including the brain. The aim of this study was to analyse the neurodegenerative effects of this metal in embryos and adults of zebrafish exposed to sub-lethal concentrations of cadmium. The study was performed by cytochemical stainings. Six hours post fertilisation (hpf) zebrafish embryos were treated for 24 hours with 9 μM of cadmium and subsequently stained with Acridine orange in whole mount to detect apoptosis in the brain. Adult zebrafish were treated for 16 days with the same concentration of cadmium, and cell death in the brain was detected by Fluoro-Jade B staining at 2, 7 and 16 days of treatment. An increase in cell death was observed only at 16 days of treatment in adults, while an increase in apoptotic events was revealed in the brain of embryos after 24 h of treatment. This evidence is indicative that cadmium, even at a sub-lethal concentration, induces cell death in the brain of embryos but also in adults of zebrafish in which the phenomenon appears time dependent

SMART DISTRICTS AS A CLIMATE RESPONSIVE STRATEGY FOR URBAN REGENERATION

In the near future, the influence of climate change on the living conditions, on indoor and outdoor comfort as well as on energy demand will assume a more increasingly importance in defining adequate and effective strategies to regenerate and renovate the built environment while supporting the transition process to a low carbon society. In this general framework, the integration of dedicated approaches in the design phases as well as the adoption of useful ICT tools to manage the complex interaction of the interrelated factors investing the urban environment represent a specific challenge. After providing a picture of the main challenges and progresses in this field, the paper describes the methodological outcomes of complementary research activities focused on the development of Smart District as a core strategy to improve the adoption of climate responsive design option both at building and district scale. This means the adoption of sustainable renovation option and energy savings measures while facilitating the integration of smart devices, sensor and controller to collect data and monitor the behaviour of buildings as well as of the shared spaces between them with the goal to increase urban quality. The paper includes some examples of how design options can be implemented into a comprehensive interactive platform, of expected impacts (energy consumption, emissions, efficiency, urban quality and environmental sustainability), of key indicators taking into account technical and non-technical barriers

Synthesis and evaluation of new pyrazole-based carboxamides as modulators of the TrPv1 channel

Since the cloning of the vanilloid receptor protein (TRPV1) by Caterina et al.,[1] this ligand gated nonselective cation channel has attracted growing interest due to its function associated with nociception signaling pathway. TRPV1 is activated by vanilloid ligands such as capsaicin and resiniferatoxin, noxious heat (> 42 °C), protons (extracellular pH < 6), and modulated by a variety of endogenous ligands including cannabinoid anandamide and arachidonic acid metabolites. TRPV1 activation enhances Ca2+ permeability that leads to an increase in intracellular Ca2+, resulting in excitation of primary sensory neurons and the central perception of pain. Activation is followed by the desensitization making the C-fiber sensory neurons unresponsive to TRPV1 agonists and other inflammatory mediators. In addition, capsazepine, the first reported antagonist of TRPV1, blocks the capsaicin-induced uptake of Ca2+ in cell-based assays. In vivo, capsazepine demonstrates species-dependent efficacies in various models of inflammatory hyperalgesia and chronic pain. [2] Therefore, both desensitization by an agonist and the direct blockade by an antagonist of TRPV1 might have therapeutic utility in the management of acute and chronic nociceptive pain. [3] Recently, a variety of TRPV1 ligands bearing a heterocyclic linker has been reported to show very interesting both in vitro and in vivo biological profiles. Based on these findings, we designed a series of pyrazole-based carboxamide analogues (Figure 1), assuming that the rigid heterocyclic linkage can induce more appropriate conformation for TRPV1 binding. figure 1 In this communication, we describe the synthesis and activities of a series of these ligands, which were screened by a cell-based assay utilizing the Ca2+ permeability of the TRPV1 channel. references 1. Caterina, M. J.; Schumacher, M. A.; Tominaga, M.; Rosen, T. A.; Levine, J. D.; Julius, D. Nature 1997, 387, 816–824. 2. Walker, K. M.; Urban, L.; Medhurst, S. J.; Patel, S.; Panesar, M.; Fox, A. J. J. Pharmacol. Exp. Ther. 2003, 304, 56-62. 3. De Petrocellis, L.; Schiano-Moriello A. Recent Pat. CNS Drug Discov. 2013, 8, 180-204 Synthesis and evaluation of new pyrazole-based carboxamides as modulators of the TRPV1 channel Cenzo Congiu,1* Valentina Onnis,1 Marco Allarà,2 Aniello Schiano-Moriello,2 Vincenzo Di Marzo,2 and Luciano De Petrocellis.2 1University of Cagliari, Department of Life and Environment Sciences, Via Ospedale 72, I-09124 – Cagliari, Italy; 2Endocannabinoid Research Group (ERG), Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, I-80078-Pozzuoli (NA), Italy Since the cloning of the vanilloid receptor protein (TRPV1) by Caterina et al.,[1] this ligand gated nonselective cation channel has attracted growing interest due to its function associated with nociception signaling pathway. TRPV1 is activated by vanilloid ligands such as capsaicin and resiniferatoxin, noxious heat (> 42 °C), protons (extracellular pH < 6), and modulated by a variety of endogenous ligands including cannabinoid anandamide and arachidonic acid metabolites. TRPV1 activation enhances Ca2+ permeability that leads to an increase in intracellular Ca2+, resulting in excitation of primary sensory neurons and the central perception of pain. Activation is followed by the desensitization making the C-fiber sensory neurons unresponsive to TRPV1 agonists and other inflammatory mediators. In addition, capsazepine, the first reported antagonist of TRPV1, blocks the capsaicin-induced uptake of Ca2+ in cell-based assays. In vivo, capsazepine demonstrates species-dependent efficacies in various models of inflammatory hyperalgesia and chronic pain.[2] Therefore, both desensitization by an agonist and the direct blockade by an antagonist of TRPV1 might have therapeutic utility in the management of acute and chronic nociceptive pain.[3] Recently, a variety of TRPV1 ligands bearing a heterocyclic linker has been reported to show very interesting both in vitro and in vivo biological profiles. Based on these findings, we designed a series of pyrazole-based carboxamide analogues (Figure 1), assuming that the rigid heterocyclic linkage can induce more appropriate conformation fo