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The year 2017 marks the 20th anniversary of the molecular cloning of the long sought-after capsaicin receptor, now known as TRPV1 (Transient Receptor Potential Vanilloid 1). This seminal discovery has opened up a "hot" new field of basic research and launched drug discovery efforts into the large family (by the latest count, 28 mammalian members and 27 in humans) of TRP ion channels. Indeed, it took less than a decade for the first potent, small molecule TRPV1 antagonists to enter phase 1 clinical trials, closely followed by TRPA1 and TRPM8 antagonists. The literature on TRP channels is immense. TRPV1 alone is a keyword in over 5000 publications searchable in PubMed. Clearly, it is not possible to capture the entire literature in a single thematic issue. Consequently, the selection of articles presented in this book represents a sampling of the literature, and is admittedly subjective. We tried to survey the wide range of human diseases in which TRP channels have been implicated, ranging from chronic pain through asthma and diabetes to cancer, and highlight the channels that appear to hold the greatest promise for therapeutic targeting. With this book, we hope to convince readers that TRP channels constitute a formidable family of potential therapeutic targets that will likely continue to demand attention.

TRP channels.

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TRP channels.

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"During the last two decades, there has been an explosion of research pertaining to the molecular mechanisms that allow for organisms to detect different stimuli that is an essential feature for their survival. Among these mechanisms, living beings need to be able to respond to different temperatures as well as chemical and physical stimuli. Thermally activated ion channels were proposed to be present in sensory neurons in the 1980s, but it was not until 1997 that a heat- and capsaicin- activated ion channel, TRPV1, was cloned and its function described in detail. This groundbreaking discovery led to the identification and characterization of several more proteins of the family of Transient Receptor Potential (TRP) ion channels. Intensive research has provided us with the atomic structures of some of these proteins, as well as understanding of their physiological roles, both in normal and pathological conditions. With chapters contributed by renowned experts in the field, Neurobiology of TRP Channels contains a state- of- the- art overview of our knowledge of TRP channels, ranging from structure to their functions in organismal physiology.? Features: Contains chapters on the roles of several TRP ion channels with a diversity of physiological functions, providing a complete picture of the widespread importance of these proteins. Presents an overview of the structure of TRP channels, including the roles of these proteins in different physiological processes. Discusses the roles of TRP channels in pathophysiological processes, further highlighting their importance. Features several full color illustrations to allow the reader better comprehension of TRP channels.A volume in the Frontiers in Neuroscience series"--Provided by publisher.

TRP channels. --- Membrane proteins. --- Ion channels. --- Neurobiology. --- Biochemistry.

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TRP channels play a key role in sensory physiology and have been the focus of intensive investigation in recent years. This book is a comprehensive, detailed overview of the ways in which TRP channels are involved in a wide variety of sensory modalities. Authors explore the involvement of TRP channels in phototransduction (sight), chemotransduction (taste and odor), mechanotransduction (touch and hearing), thermotransduction (the sensation of temperature), and pain perception. Furthermore, the book includes some grounding chapters such as one on the history of TRP channel research, one on the biophysical characteristics of the proteins, and one on trafficking and post-translational regulation.

Biomedicine. --- Neurosciences. --- Human Physiology. --- Neurobiology. --- Medicine. --- Human physiology. --- Médecine --- Physiologie humaine --- Neurosciences --- Neurobiologie --- Neurology --- Medicine --- Health & Biological Sciences --- TRP channels. --- Senses and sensation. --- Sensation --- Sensory biology --- Sensory systems --- Transient receptor potential channels --- TRP proteins --- Knowledge, Theory of --- Neurophysiology --- Psychophysiology --- Perception --- Ion channels --- Membrane proteins --- Human biology --- Medical sciences --- Physiology --- Human body --- Neural sciences --- Neurological sciences --- Neuroscience --- Nervous system

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Depuis quelques années un manque de puissance a été mis au jour dans divers domaines de recherche. Cela a abouti à de sérieux doutes quant à la reproductibilité de beaucoup de résultats scientifiques. À notre connaissance, aucune étude n’a évalué ce problème en psychopharmacologie expérimentale préclinique. Nous avons choisi d’étudier le sous-domaine de la préférence de lieu conditionné induite par la nicotine chez la souris (PLCNIC).
Nous avons identifié les articles le concernant sur PubMed et nous en avons extrait les tailles des échantillons, le type de tests statistiques (F ou t), leurs résultats, leurs degrés de liberté, et leurs p-valeurs. À partir de ces valeurs, nous avons calculé la puissance prospective médiane pour 6 tailles d’effets (classification de Sawilowsky, 2009). Le taux de vraies découvertes (True Report Probability : TRP) a été calculé à partir des puissances médianes, de l’erreur de type I fixée à 5 %, et de la plausibilité que nous avons fait varier de 0 à 1.
Des 139 articles trouvés sur PubMed, 48 ont rencontré nos critères d’inclusion. Ces 48 articles contenaient 109 tests statistiques utilisables pour notre projet. Dans cet échantillon de tests 77,57 % sont significatifs. Les puissances médianes pour les tests F pour les petites, moyennes, et grandes tailles d’effet sont respectivement de 9,5 %, 34,1 % et 70,4 %. Pour les tests t nous avons trouvé 6,8 %, 17 %, et 35,8 %. Aucun de ces chiffres n’atteint le seuil recommandé de 80 %. Pour une plausibilité de 10 %, nous trouvons des TRP pour les tests F pour une petite, moyenne et grande taille d’effet de 16 % 40,8 %, et 58,5 % soit des taux de fausses découvertes de 84 %, 59,2 %, et 41,5 %. Pour les tests t les TRP pour les mêmes tailles d’effets sont de 12 %, 25,3 %, et 41,7 % soit des taux de fausses découvertes de 88 %, 74,7 %, et 58,3 %, bien supérieurs aux 5 % maximum que l’on croit garantis par la probabilité alpha.
Nous retrouvons donc, dans le sous-domaine de la PLCNIC, le manque de puissance et l’augmentation de faux positif associée qui ont déjà été observés dans d’autres disciplines.
Nous avons aussi étendu les graphiques de Ioannidis (2005) pour représenter les TRP qu’on obtient avec des rapports de chance supérieurs à 1/1 qui pourrait donner des TRP plus favorables.

Mice --- Statistical power --- meta-research --- conditioned place preference --- nicotine --- FDR --- TRP --- false discovery rate --- true report probability --- souris --- puissance statistique --- méta-recherche --- préférence de lieu conditionné --- nicotine --- FDR --- TRP --- Taux de fausses découvertes --- taux de vraies découvertes --- Sciences sociales & comportementales, psychologie > Psychologie animale, éthologie & psychobiologie --- Sciences sociales & comportementales, psychologie > Neurosciences & comportement