90 research outputs found

    5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice

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    <p>Abstract</p> <p>Background</p> <p>The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds.</p> <p>Results</p> <p>In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat thereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p-CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wild-type mice.</p> <p>Conclusion</p> <p>Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.</p

    FAIR Metadata Standards for Low Carbon Energy Research—A Review of Practices and How to Advance

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    The principles of Findability, Accessibility, Interoperability, and Reusability (FAIR) have been put forward to guide optimal sharing of data. The potential for industrial and social innovation is vast. Domain-specific metadata standards are crucial in this context, but are widely missing in the energy sector. This report provides a collaborative response from the low carbon energy research community for addressing the necessity of advancing FAIR metadata standards. We review and test existing metadata practices in the domain based on a series of community workshops. We reflect the perspectives of energy data stakeholders. The outcome is reported in terms of challenges and elicits recommendations for advancing FAIR metadata standards in the energy domain across a broad spectrum of stakeholders

    5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

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    oai:ojs.pkp.sfu.ca:article/31555-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [194] and subsequently revised [176]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [463, 382])

    5-Hydroxytryptamine receptors in GtoPdb v.2023.1

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    5-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [198] and subsequently revised [180]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 491]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [471, 387])

    Evolution of pathogenicity and sexual reproduction in eight Candida genomes

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    Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.publishe

    Connecting photometric and spectroscopic granulation signals with CHEOPS and ESPRESSO

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    Context. Stellar granulation generates fluctuations in photometric and spectroscopic data whose properties depend on the stellar type, composition, and evolutionary state. Characterizing granulation is key for understanding stellar atmospheres and detecting planets. Aims. We aim to detect the signatures of stellar granulation, link spectroscopic and photometric signatures of convection for main-sequence stars, and test predictions from 3D hydrodynamic models. Methods. For the first time, we observed two bright stars (Teff = 5833 and 6205 K) with high-precision observations taken simultaneously with CHEOPS and ESPRESSO. We analyzed the properties of the stellar granulation signal in each individual dataset. We compared them to Kepler observations and 3D hydrodynamic models. While isolating the granulation-induced changes by attenuating and filtering the p-mode oscillation signals, we studied the relationship between photometric and spectroscopic observables. Results. The signature of stellar granulation is detected and precisely characterized for the hotter F star in the CHEOPS and ESPRESSO observations. For the cooler G star, we obtain a clear detection in the CHEOPS dataset only. The TESS observations are blind to this stellar signal. Based on CHEOPS observations, we show that the inferred properties of stellar granulation are in agreement with both Kepler observations and hydrodynamic models. Comparing their periodograms, we observe a strong link between spectroscopic and photometric observables. Correlations of this stellar signal in the time domain (flux versus radial velocities, RV) and with specific spectroscopic observables (shape of the cross-correlation functions) are however difficult to isolate due to S/N dependent variations. Conclusions. In the context of the upcoming PLATO mission and the extreme precision RV surveys, a thorough understanding of the properties of the stellar granulation signal is needed. The CHEOPS and ESPRESSO observations pave the way for detailed analyses of this stellar process

    Examining the orbital decay targets KELT-9 b, KELT-16 b, and WASP-4 b, and the transit-timing variations of HD 97658 b,

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    Context. Tidal orbital decay is suspected to occur for hot Jupiters in particular, with the only observationally confirmed case of this being WASP-12 b. By examining this effect, information on the properties of the host star can be obtained using the so-called stellar modified tidal quality factor Q′∗, which describes the efficiency with which the kinetic energy of the planet is dissipated within the star. This can provide information about the interior of the star. Aims. In this study, we aim to improve constraints on the tidal decay of the KELT-9, KELT-16, and WASP-4 systems in order to find evidence for or against the presence of tidal orbital decay. With this, we want to constrain the Q′∗ value for each star. In addition, we aim to test the existence of the transit timing variations (TTVs) in the HD 97658 system, which previously favoured a quadratic trend with increasing orbital period. Methods. Making use of newly acquired photometric observations from CHEOPS (CHaracterising ExOplanet Satellite) and TESS (Transiting Exoplanet Survey Satellite), combined with archival transit and occultation data, we use Markov chain Monte Carlo (MCMC) algorithms to fit three models to the data, namely a constant-period model, an orbital-decay model, and an apsidal-precession model. Results. We find that the KELT-9 system is best described by an apsidal-precession model for now, with an orbital decay trend at over 2 σ being a possible solution as well. A Keplerian orbit model with a constant orbital period provides the best fit to the transit timings of KELT-16 b because of the scatter and scale of their error bars. The WASP-4 system is best represented by an orbital decay model at a 5 σ significance, although apsidal precession cannot be ruled out with the present data. For HD 97658 b, using recently acquired transit observations, we find no conclusive evidence for a previously suspected strong quadratic trend in the data

    TOI-1055 b: Neptunian planet characterised with HARPS, TESS, and CHEOPS

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    Context. TOI-1055 is a Sun-like star known to host a transiting Neptune-sized planet on a 17.5-day orbit (TOI-1055 b). Radial velocity (RV) analyses carried out by two independent groups using nearly the same set of HARPS spectra have provided measurements of planetary masses that differ by ∼2σ. Aims. Our aim in this work is to solve the inconsistency in the published planetary masses by significantly extending the set of HARPS RV measurements and employing a new analysis tool that is able to account and correct for stellar activity. Our further aim was to improve the precision on measurements of the planetary radius by observing two transits of the planet with the CHEOPS space telescope. Methods. We fit a skew normal function to each cross correlation function extracted from the HARPS spectra to obtain RV measurements and hyperparameters to be used for the detrending. We evaluated the correlation changes of the hyperparameters along the RV time series using the breakpoint technique. We performed a joint photometric and RV analysis using a Markov chain Monte Carlo scheme to simultaneously detrend the light curves and the RV time series. Results. We firmly detected the Keplerian signal of TOI-1055 b, deriving a planetary mass of Mb = 20.4-2.5+2.6 MO (∼12%). This value is in agreement with one of the two estimates in the literature, but it is significantly more precise. Thanks to the TESS transit light curves combined with exquisite CHEOPS photometry, we also derived a planetary radius of Rb = 3.490-0.064+0.070 RO (∼1.9%). Our mass and radius measurements imply a mean density of ρb = 2.65-0.35+0.37 g cm-3 (∼14%). We further inferred the planetary structure and found that TOI-1055 b is very likely to host a substantial gas envelope with a mass of 0.41-0.20+0.34 MO and a thickness of 1.05-0.29+0.30 RO. Conclusions. Our RV extraction combined with the breakpoint technique has played a key role in the optimal removal of stellar activity from the HARPS time series, enabling us to solve the tension in the planetary mass values published so far for TOI-1055 b
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