Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin

Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance

Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes

The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system

The CARMENES search for exoplanets around M dwarfs High-resolution optical and near-infrared spectroscopy of 324 survey stars

The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M dwarf. These spectra cover the wavelength range 520–1710 nm at a resolution of at least R >80 000, and we measure its RV, Hα emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content, Q, and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700–900 nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1 m s−1 in very low mass M dwarfs at longer wavelengths likely requires the use of a 10 m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4 m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3–4 m s−1

A giant exoplanet orbiting a very-low-mass star challenges planet formation models

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought

CARMENES: high-resolution spectra and precise radial velocities in the red and infrared

SPIE Astronomical Telescopes + Instrumentation (2018, Austin, Texas, United States

Avaliação do risco nutricional em idosos atendidos por Equipes de Saúde da Família Evaluación del riesgo nutricional en ancianos atendidos por Equipos de Salud de Familia Evaluation of the nutritional risk in elderly assisted by Family Health Teams

Alterações do estado nutricional contribuem para o aumento da morbi-mortalidade em idosos. O instrumento The Nutrition Screening Initiative (NSI) foi desenvolvido para identificar riscos nutricionais nesse grupo populacional. Este estudo tem por objetivos descrever o perfil sociodemográfico e avaliar o risco nutricional de idosos atendidos por equipes da Estratégia Saúde da Família. O estudo é transversal, com amostra de 503 idosos residentes em Dourados (MS). Instrumentos: NSI e questionário estruturado para as variáveis sociodemográficas de saúde. Verificou-se o predomínio de idosos do sexo feminino, entre 60 a 69 anos, viúvos, analfabetos, de renda per capita de até um salário mínimo, com hipertensão e auto-avaliação regular de saúde. O NSI permitiu identificar 33,2% de idosos com alto risco nutricional, o que se mostrou significativamente associado ao baixo nível de escolaridade, à baixa renda per capita e às doenças crônicas. Como método de rastreio, o NSI mostrou-se útil para identificar os determinantes sociais e de saúde que contribuem para o risco nutricional.<br>Las alteraciones del estado nutricional contribuyen en aumentar la morbimortalidad en ancianos. El instrumento The Nutririon Screening Inititative (NSI) fue desarrollado para identificar riesgos nutricionales en dicho grupo poblacional. Este estudio tiene como objetivos describir el perfil socio-demográfico y evaluar el riesgo nutricional de ancianos atendidos por equipos de la Estrategia Salud de la Familia. Estudio transversal, con muestra de 503 ancianos residentes en Dourados - MS - Brasil. Instrumentos: NSI y cuestionario estructurado para las variables socio-demográficas y de salud. Se verificó el predominio de ancianos del sexo femenino, de 60 a 69 años, viudos, analfabetos, con ingresos per cápita de hasta un salario mínimo, con hipertensión y autoevaluación regular de salud. El NSI permitió identificar un 33,2% de ancianos con alto riesgo nutricional, que se mostró significativamente asociado a: bajo nivel de escolaridad, bajos ingresos per cápita de hasta un salario mínimo y enfermedades crónicas. Como método de rastreo, el NSI se mostró útil para identificar los determinantes sociales y sanitarios que contribuyen al riesgo nutricional.<br>Changes in the nutritional state contribute to an increase of morbi-mortality among the elderly. The instrument Nutrition Screening Initiative (NSI) was developed in order to identify nutritional risks in this population group. This study aims to describe the socio-demographic profile and evaluate the nutritional risk of the elderly assisted by Family Health Strategy teams. It is a cross-sectional study with a sample of 503 older people living in Dourados (MS). Instruments: NSI and structured questionnaire for the health socio-demographic variables. There was a prevalence of female people, aged between 60 and 69 years old, widowers, illiterate, with a per capita income up to one minimum salary, with hypertension and regular health self-evaluation. The NSI allowed to identify 33.2% of the elderly with high nutritional risk, which was significantly associated to the low level of education, low per capita income and chronic diseases. As a tracking method, the NSI was useful to identify the social and health determinants that contribute to the nutritional risk

Envelhecimento, estratégias de enfrentamento do idoso e repercussões na família Envejecimiento, estrategias de afrontamiento de los ancianos y impactos en la familia Aging, facing strategies of the aged and the consequences for family

Trata-se de estudo qualitativo para conhecer a percepção de idosos, usuários de Unidade Básica de Saúde de São Paulo, sobre envelhecimento, estratégias de enfrentamento e repercussões na família. Foram realizadas, de setembro de 2007 a julho de 2008, entrevistas com três idosos, de 71 a 90 anos. Os participantes responderam às perguntas da Escala de Depressão Geriátrica, Ecomapa, Genograma e modelo Calgary. Com análise de conteúdo de Bardin, encontramos três categorias percebendo o momento do ciclo vital; sofrendo as repercussões deste momento; enfrentando o envelhecimento e a velhice. Acreditamos na continuidade de estudos que busquem estratégias com idosos e famílias na tentativa de melhorar a qualidade de vida e dinâmica familiar com inclusão de entretenimento, segundo possibilidade da comunidade.<br>El siguiente estudio cualitativo busca comprender la percepción de las personas de edad avanzada, usuarios de la Unidad Básica de Salud de São Paulo, en cuanto al envejecimiento, estrategias de afrontamiento y el impacto en la familia. Se hicieron entrevistas desde Septiembre del 2007 hacia Julio del 2008 con tres personas mayores, de los 71 a 90 años. Los participantes contestaron a las preguntas de la Escala de Depresión Geriátrica, Ecomapa, Genograma y modelo Calgary. A través del análisis de Bardin, hemos descubierto tres categorías - el momento de darse cuenta del ciclo de la vida; se sufren las consecuencias de ese momento; se enfrentan el proceso de envejecimiento y la vejez. Creemos en la continuidad de los estudios que buscan estrategias con las personas mayores y sus familias para mejorar la calidad de vida y la dinámica familiar a través de la inclusión del entretenimiento, acuerdo a las posibilidades ofrecidas a la comunidad.<br>This qualitative study seeks the understanding of the perception of the elderly, users of Basic Health Unit of São Paulo, on aging, coping strategies and impact on family. Interviews with three elderly people, from 71 to 90 years-old, were held from September 2007 to July'2008. Participants responded to questions under the Geriatric Depression Scale, Ecomapa, Genogram and Calgary model. From the Bardin analysis, we could determine three categories - the moment of realizing the life cycle; suffering the consequences of this time; facing the aging and old age. We believe in the continuity of studies that search for strategies with older people and their families in an attempt to improve life quality and family dynamics by the inclusion of entertainment, according to the possibilities offered to their communities