Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume

Ependymal cell cilia help move cerebrospinal fluid through the cerebral ventricles, but the regulation of their beat frequency remains unclear. Using in vitro, high-speed video microscopy and in vivo magnetic resonance imaging in mice, we found that the metabolic peptide melanin-concentrating hormone (MCH) positively controlled cilia beat frequency, specifically in the ventral third ventricle, whereas a lack of MCH receptor provoked a ventricular size increase.

Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior

BACKGROUND There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. Using a pharmacogenetic approach, we investigated how variation in this gene modulates the impact of dopaminergic stimulation on gambling behavior in healthy subjects. METHODS We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration. RESULTS Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individual's DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation. CONCLUSIONS These findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinson's disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.

DAT1 polymorphism determines L-DOPA effects on learning about others' prosociality.

Despite that a wealth of evidence links striatal dopamine to individualś reward learning performance in non-social environments, the neurochemical underpinnings of such learning during social interaction are unknown. Here, we show that the administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male subjects influences learning about a partners' prosocial preferences in a novel social interaction task, which is akin to a repeated trust game. We found learning to be modulated by a well-established genetic marker of striatal dopamine levels, the 40-bp variable number tandem repeats polymorphism of the dopamine transporter (DAT1 polymorphism). In particular, we found that L-DOPA improves learning in 10/10R genoype subjects, who are assumed to have lower endogenous striatal dopamine levels and impairs learning in 9/10R genotype subjects, who are assumed to have higher endogenous dopamine levels. These findings provide first evidence for a critical role of dopamine in learning whether an interaction partner has a prosocial or a selfish personality. The applied pharmacogenetic approach may open doors to new ways of studying psychiatric disorders such as psychosis, which is characterized by distorted perceptions of others' prosocial attitudes.

Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R

Melanin-concentrating hormone (MCH) is a 19-aa cyclic neuropeptide originally isolated from chum salmon pituitaries. Besides its effects on the aggregation of melanophores in fish several lines of evidence suggest that in mammals MCH functions as a regulator of energy homeostasis. Recently, several groups reported the identification of an orphan G protein-coupled receptor as a receptor for MCH (MCH-1R). We hereby report the identification of a second human MCH receptor termed MCH-2R, which shares about 38% amino acid identity with MCH-1R. MCH-2R displayed high-affinity MCH binding, resulting in inositol phosphate turnover and release of intracellular calcium in mammalian cells. In contrast to MCH-1R, MCH-2R signaling is not sensitive to pertussis toxin and MCH-2R cannot reduce forskolin-stimulated cAMP production, suggesting an exclusive Gαq coupling of the MCH-2R in cell-based systems. Northern blot and in situ hybridization analysis of human and monkey tissue shows that expression of MCH-2R mRNA is restricted to several regions of the brain, including the arcuate nucleus and the ventral medial hypothalamus, areas implicated in regulation of body weight. In addition, the human MCH-2R gene was mapped to the long arm of chromosome 6 at band 6q16.2–16.3, a region reported to be associated with cytogenetic abnormalities of obese patients. The characterization of a second mammalian G protein-coupled receptor for MCH potentially indicates that the control of energy homeostasis in mammals by the MCH neuropeptide system may be more complex than initially anticipated.

Identification and characterization of a melanin-concentrating hormone receptor

Melanin-concentrating hormone (MCH), a neuropeptide expressed in central and peripheral nervous systems, plays an important role in the control of feeding behaviors and energy metabolism. An orphan G protein-coupled receptor (SLC-1/GPR24) has recently been identified as a receptor for MCH (MCHR1). We report here the identification and characterization of a G protein-coupled receptor as the MCH receptor subtype 2 (MCHR2). MCHR2 has higher protein sequence homology to MCHR1 than any other G protein-coupled receptor. The expression of MCHR2 has been detected in many regions of the brain. In contrast to MCHR1, which is intronless in the coding region and is located at the chromosomal locus 22q13.3, the MCHR2 gene has multiple exons and is mapped to locus 6q21. MCHR2 is specifically activated by nanomolar concentrations of MCH, binds to MCH with high affinity, and signals through Gq protein. This discovery is important for a full understanding of MCH biology and the development of potential therapeutics for diseases involving MCH, including obesity.

Study of optical properties of electropolymerized melanin films by photopyroelectric spectroscopy

Photopyroelectric (PPE) spectroscopy, in the 350-1,075 nm wavelength range, was used to study the optical properties of electropolymerized melanin films on indium tin oxide (ITO) coated glass. The PPE intensity signal as a function of the wavelength lambda, V (n)(lambda) and its phase F (n)(lambda) were independently measured. Using the PPE signal intensity and the thermal and optical properties of the pyroelectric detector, we were able to calculate the optical absorption coefficient beta of melanin in the solid-state. We believe this to be the first such measurement of its kind on this material. Additionally, we found an optical gap in these melanin films at 1.70 eV.

Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin

Cultured human melanocytes differ tremendously in visual pigmentation, and recapitulate the pigmentary phenotype of the donor's skin. This diversity arises from variation in type as well as quantity of melanin produced. Here, we measured contents of eumelanin (EM) and pheomelanin (PM) in 60 primary human melanocyte cultures (51 neonatal and nine adults), and correlated some of these values with the respective activity and protein levels of tyrosinase, and the melanocortin-1 receptor (MC1R) genotype. Melanocytes were classified into four phenotypes (L, L+, D, D+) as depicted by visual pigmentation using light microscopy, and by the pigmentary phenotype of the donor's skin. There were large differences in total melanin (TM) and EM, which increased progressively for L, L+, D and D+ melanocytes. TM content, the sum of EM and PM, showed a good correlation with TM measured spectrophotometrically, and with the activity and protein levels of tyrosinase. Log EM/PM ratio did not correlate with MC1R genotype. We conclude that: (i) EM consistently correlates with the visual phenotype; (ii) lighter melanocytes tend to be more pheomelanic in composition than darker melanocytes; (iii) in adult melanocyte cultures, EM correlates with the ethnic background of the donors (African-American > Indian > Caucasian); and (iv) MC1R loss-of-function mutations do not necessarily alter the phenotype of cultured melanocytes.

Quantitative scattering of melanin solutions

The optical scattering coefficient of a dilute, well-solubilized eumelanin solution has been accurately measured as a function of incident wavelength, and found to contribute < 6% of the total optical attenuation between 210 and 325 nm. At longer wavelengths (325-800 nm), the scattering was less than the minimum sensitivity of our instrument. This indicates that ultraviolet and visible optical density spectra can be interpreted as true absorption with a high degree of confidence. The scattering coefficient versus wavelength was found to be consistent with Rayleigh theory for a particle radius of 38 6 1 nm. Our results shed important light on the role of melanins as photoprotectants.

Complexation in composite solutions of melanin with 2,4,7-trinitrofluorenone

A feasibility of formation of donor-acceptor charge-transfer (CT) complexes between melanin and 2,4,7-trinitrofluorenone (TNF) being good electron acceptor has been studied in solutions by means of the absorption and photoluminescence (PL) spectra. The model of electronic transitions in a melanin-TNF composite solution has been proposed. © 2014 Copyright Taylor & Francis Group, LLC.

The Digital Observatory for Protected Areas (DOPA) Explorer 1.0

The Digital Observatory for Protected Areas (DOPA) has been developed to support the European Union’s efforts in strengthening our capacity to mobilize and use biodiversity data, information and forecasts so that they are readily accessible to policymakers, managers, experts and other users. Conceived as a set of web based services, DOPA provides a broad set of free and open source tools to assess, monitor and even forecast the state of and pressure on protected areas at local, regional and global scale. DOPA Explorer 1.0 is a web based interface available in four languages (EN, FR, ES, PT) providing simple means to explore the nearly 16,000 protected areas that are at least as large as 100 km2. Distinguishing between terrestrial, marine and mixed protected areas, DOPA Explorer 1.0 can help end users to identify those with most unique ecosystems and species, and assess the pressures they are exposed to because of human development. Recognized by the UN Convention on Biological Diversity (CBD) as a reference information system, DOPA Explorer is based on the best global data sets available and provides means to rank protected areas at the country and ecoregion levels. Inversely, DOPA Explorer indirectly highlights the protected areas for which information is incomplete. We finally invite the end-users of DOPA to engage with us through the proposed communication platforms to help improve our work to support the safeguarding of biodiversity.

The Digital Observatory for Protected Areas (DOPA) as a support tool for protected area planning, financing and reporting

The Joint Research Centre (JRC) of the European Commission has developed, in consultation with many partners, the DOPA as a global reference information system to support decision making on protected areas (PAs) and biodiversity conservation. The DOPA brings together the World Database on Protected Areas with other reference datasets on species, habitats, ecoregions, threats and pressures, to deliver critical indicators at country level and PA level that can inform gap analyses, PA planning and reporting. These indicators are especially relevant to Aichi Targets 11 and 12, and have recently contributed to CBD country dossiers and capacity building on these targets. DOPA also includes eConservation, a new module that provides a means to share and search information on conservation projects, and thus allows users to see “who is doing what where”. So far over 5000 projects from the World Bank, GEF, CEPF, EU LIFE Programme, CBD LifeWeb Initiative and others have been included, and these projects can be searched in an interactive mapping interface based on criteria such as location, objectives, timeframe, budget, the organizations involved, target species etc. This seminar will provide an introduction to DOPA and eConservation, highlight how these services are used by the CBD and others, and include ample time for discussion.

Ferroelectric-like behaviour of melanin:humidity effect on current-voltage characteristics

The influence of low vacuum on quasistatic current-voltage (I–V) dependences and the impact of wet air pulse on dynamic bipolar I-V-loops and unipolar I-V-curves of fungal melanin thin layers have been studied for the first time. The threshold hysteresis voltages of I–V dependences are near to the standard electrode potentials of anodic water decomposition. Short wet air pulse impact leads to sharp increase of the current and appearance of “hump”-like and “knee”-like features of I-V-loops and I-V-curves, respectively. By treatment of I-V-loop allowing for I-V-curve shape the maxima of displacement current are revealed. The peculiarities of I-V-characteristics were modelled by series-parallel RC-circuit with Zener diodes as nonlinear elements. As a reason of appearance of temporal polar media with reversible ferroelectric-like polarization and ionic space charge transfer is considered the water-assisted dissociation of some ionic groups of melanin monomers that significantly influences electrophysical parameters of melanin nanostructures.

Síntese e caracterização de complexos de Co(II) e Ni(II) com l-dopa, carbidopa e benzimidazol

Were synthesized in this work in the following aqueous solution coordination compounds: [Ni(LDP)(H2O)2Cl2].2H2O, [Co(LDP)Cl2].3H2O, [Ni(CDP)Cl2].4H2O, [Co(CDP)Cl2].4H2O, [Ni(BDZ)2Cl2].4H2O and [Co(BDZ)2Cl2(H2O)2]. These complexes were synthesized by stoichiometric addition of the binder in the respective metal chloride solutions. Precipitation occurred after drying the solvent at room temperature. The characterization and proposed structures were made using conventional analysis methods such as elemental analysis (CHN), absorption spectroscopy in the infrared Fourier transform spectroscopy (FTIR), X-ray diffraction by the powder method and Technical thermoanalytical TG / DTG (thermogravimetry / derivative thermogravimetry) and DSC (differential scanning calorimetry). These techniques provided information on dehydration, coordination modes, thermal performance, composition and structure of the synthesized compounds. The results of the TG curve, it was possible to establish the general formula of each compound synthesized. The analysis of X-ray diffraction was observed that four of the synthesized complex crystal structure which does not exhibit the complex was obtained from Ldopa and carbidopa and the complex obtained from benzimidazole was obtained crystal structures. The observations of the spectra in the infrared region suggested a monodentate ligand coordination to metal centers through its amine group for all complexes. The TG-DTG and DSC curves provide important information and on the behavior and thermal decomposition of the synthesized compounds. The molar conductivity data indicated that the solutions of the complexes formed behave as a nonelectrolyte, which implies that chlorine is coordinated to the central atom in the complex.

Síntese e caracterização de complexos de Co(II) e Ni(II) com l-dopa, carbidopa e benzimidazol

Were synthesized in this work in the following aqueous solution coordination compounds: [Ni(LDP)(H2O)2Cl2].2H2O, [Co(LDP)Cl2].3H2O, [Ni(CDP)Cl2].4H2O, [Co(CDP)Cl2].4H2O, [Ni(BDZ)2Cl2].4H2O and [Co(BDZ)2Cl2(H2O)2]. These complexes were synthesized by stoichiometric addition of the binder in the respective metal chloride solutions. Precipitation occurred after drying the solvent at room temperature. The characterization and proposed structures were made using conventional analysis methods such as elemental analysis (CHN), absorption spectroscopy in the infrared Fourier transform spectroscopy (FTIR), X-ray diffraction by the powder method and Technical thermoanalytical TG / DTG (thermogravimetry / derivative thermogravimetry) and DSC (differential scanning calorimetry). These techniques provided information on dehydration, coordination modes, thermal performance, composition and structure of the synthesized compounds. The results of the TG curve, it was possible to establish the general formula of each compound synthesized. The analysis of X-ray diffraction was observed that four of the synthesized complex crystal structure which does not exhibit the complex was obtained from Ldopa and carbidopa and the complex obtained from benzimidazole was obtained crystal structures. The observations of the spectra in the infrared region suggested a monodentate ligand coordination to metal centers through its amine group for all complexes. The TG-DTG and DSC curves provide important information and on the behavior and thermal decomposition of the synthesized compounds. The molar conductivity data indicated that the solutions of the complexes formed behave as a nonelectrolyte, which implies that chlorine is coordinated to the central atom in the complex.