Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia

Inflammatory proteases (mast cell tryptase and trypsins) cleave protease-activated receptor 2 (PAR2) on spinal afferent neurons and cause persistent inflammation and hyperalgesia by unknown mechanisms. We determined whether transient receptor potential vanilloid receptor 1 (TRPV1), a cation channel activated by capsaicin, protons, and noxious heat, mediates PAR2-induced hyperalgesia. PAR2 was coexpressed with TRPV1 in small- to medium-diameter neurons of the dorsal root ganglia (DRG), as determined by immunofluorescence. PAR2 agonists increased intracellular [Ca2+] ([Ca2+]i) in these neurons in culture, and PAR2-responsive neurons also responded to the TRPV1 agonist capsaicin, confirming coexpression of PAR2 and TRPV1. PAR2 agonists potentiated capsaicin-induced increases in [Ca2+]i in TRPV1-transfected human embryonic kidney (HEK) cells and DRG neurons and potentiated capsaicin-induced currents in DRG neurons. Inhibitors of phospholipase C and protein kinase C (PKC) suppressed PAR2-induced sensitization of TRPV1-mediated changes in [Ca2+]i and TRPV1 currents. Activation of PAR2 or PKC induced phosphorylation of TRPV1 in HEK cells, suggesting a direct regulation of the channel. Intraplantar injection of a PAR2 agonist caused persistent thermal hyperalgesia that was prevented by antagonism or deletion of TRPV1. Coinjection of nonhyperalgesic doses of PAR2 agonist and capsaicin induced hyperalgesia that was inhibited by deletion of TRPV1 or antagonism of PKC. PAR2 activation also potentiated capsaicin-induced release of substance P and calcitonin gene-related peptide from superfused segments of the dorsal horn of the spinal cord, where they mediate hyperalgesia. We have identified a novel mechanism by which proteases that activate PAR2 sensitize TRPV1 through PKC. Antagonism of PAR2, TRPV1, or PKC may abrogate protease-induced thermal hyperalgesia

Translating clinical training into practice in complex mental health systems: Toward opening the 'Black Box' of implementation

<p>Abstract</p> <p>Background</p> <p>Implementing clinical training in a complex health care system is challenging. This report describes two successive trainings programs in one Veterans Affairs healthcare network and the lessons we drew from their success and failures. The first training experience led us to appreciate the value of careful implementation planning while the second suggested that use of an external facilitator might be an especially effective implementation component. We also describe a third training intervention in which we expect to more rigorously test our hypothesis regarding the value of external facilitation.</p> <p>Results</p> <p>Our experiences appear to be consonant with the implementation model proposed by Fixsen. In this paper we offer a modified version of the Fixsen model with separate components related to training and implementation.</p> <p>Conclusion</p> <p>This report further reinforces what others have noted, namely that educational interventions intended to change clinical practice should employ a multilevel approach if patients are to truly benefit from new skills gained by clinicians. We utilize an implementation research model to illustrate how the aims of the second intervention were realized and sustained over the 12-month follow-up period, and to suggest directions for future implementation research. The present report attests to the validity of, and contributes to, the emerging literature on implementation research.</p

Species-specific, pan-European diameter increment models based on data of 2.3 million trees

ResearchBackground: Over the last decades, many forest simulators have been developed for the forests of individual European countries. The underlying growth models are usually based on national datasets of varying size, obtained from National Forest Inventories or from long-term research plots. Many of these models include country- and location-specific predictors, such as site quality indices that may aggregate climate, soil properties and topography effects. Consequently, it is not sensible to compare such models among countries, and it is often impossible to apply models outside the region or country they were developed for. However, there is a clear need for more generically applicable but still locally accurate and climate sensitive simulators at the European scale, which requires the development of models that are applicable across the European continent. The purpose of this study is to develop tree diameter increment models that are applicable at the European scale, but still locally accurate. We compiled and used a dataset of diameter increment observations of over 2.3 million trees from 10 National Forest Inventories in Europe and a set of 99 potential explanatory variables covering forest structure, weather, climate, soil and nutrient deposition. Results: Diameter increment models are presented for 20 species/species groups. Selection of explanatory variables was done using a combination of forward and backward selection methods. The explained variance ranged from 10% to 53% depending on the species. Variables related to forest structure (basal area of the stand and relative size of the tree) contributed most to the explained variance, but environmental variables were important to account for spatial patterns. The type of environmental variables included differed greatly among species. Conclusions: The presented diameter increment models are the first of their kind that are applicable at the European scale. This is an important step towards the development of a new generation of forest development simulators that can be applied at the European scale, but that are sensitive to variations in growing conditions and applicable to a wider range of management systems than before. This allows European scale but detailed analyses concerning topics like CO2 sequestration, wood mobilisation, long term impact of management, etcinfo:eu-repo/semantics/publishedVersio

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

A Synoptical Classification of the Bivalvia (Mollusca)

The following classification summarizes the suprageneric taxono-my of the Bivalvia for the upcoming revision of the Bivalvia volumes of the Treatise on Invertebrate Paleontology, Part N. The development of this classification began with Carter (1990a), Campbell, Hoeks-tra, and Carter (1995, 1998), Campbell (2000, 2003), and Carter, Campbell, and Campbell (2000, 2006), who, with assistance from the United States National Science Foundation, conducted large-scale morphological phylogenetic analyses of mostly Paleozoic bivalves, as well as molecular phylogenetic analyses of living bivalves. Dur-ing the past several years, their initial phylogenetic framework has been revised and greatly expanded through collaboration with many students of bivalve biology and paleontology, many of whom are coauthors. During this process, all available sources of phylogenetic information, including molecular, anatomical, shell morphological, shell microstructural, bio- and paleobiogeographic as well as strati-graphic, have been integrated into the classification. The more recent sources of phylogenetic information include, but are not limited to, Carter (1990a), Malchus (1990), J. Schneider (1995, 1998a, 1998b, 2002), T. Waller (1998), Hautmann (1999, 2001a, 2001b), Giribet and Wheeler (2002), Giribet and Distel (2003), Dreyer, Steiner, and Harper (2003), Matsumoto (2003), Harper, Dreyer, and Steiner (2006), Kappner and Bieler (2006), Mikkelsen and others (2006), Neulinger and others (2006), Taylor and Glover (2006), Kříž (2007), B. Morton (2007), Taylor, Williams, and Glover (2007), Taylor and others (2007), Giribet (2008), and Kirkendale (2009). This work has also benefited from the nomenclator of bivalve families by Bouchet and Rocroi (2010) and its accompanying classification by Bieler, Carter, and Coan (2010).This classification strives to indicate the most likely phylogenetic position for each taxon. Uncertainty is indicated by a question mark before the name of the taxon. Many of the higher taxa continue to undergo major taxonomic revision. This is especially true for the superfamilies Sphaerioidea and Veneroidea, and the orders Pectinida and Unionida. Because of this state of flux, some parts of the clas-sification represent a compromise between opposing points of view. Placement of the Trigonioidoidea is especially problematic. This Mesozoic superfamily has traditionally been placed in the order Unionida, as a possible derivative of the superfamily Unionoidea (see Cox, 1952; Sha, 1992, 1993; Gu, 1998; Guo, 1998; Bieler, Carter, & Coan, 2010). However, Chen Jin-hua (2009) summarized evi-dence that Trigonioidoidea was derived instead from the superfamily Trigonioidea. Arguments for these alternatives appear equally strong, so we presently list the Trigonioidoidea, with question, under both the Trigoniida and Unionida, with the contents of the superfamily indicated under the Trigoniida.Fil: Carter, Joseph G.. University of North Carolina; Estados UnidosFil: Altaba, Cristian R.. Universidad de las Islas Baleares; EspañaFil: Anderson, Laurie C.. South Dakota School of Mines and Technology; Estados UnidosFil: Araujo, Rafael. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; EspañaFil: Biakov, Alexander S.. Russian Academy of Sciences; RusiaFil: Bogan, Arthur E.. North Carolina State Museum of Natural Sciences; Estados UnidosFil: Campbell, David. Paleontological Research Institution; Estados UnidosFil: Campbell, Matthew. Charleston Southern University; Estados UnidosFil: Chen, Jin Hua. Chinese Academy of Sciences. Nanjing Institute of Geology and Palaeontology; República de ChinaFil: Cope, John C. W.. National Museum of Wales. Department of Geology; Reino UnidoFil: Delvene, Graciela. Instituto Geológico y Minero de España; EspañaFil: Dijkstra, Henk H.. Netherlands Centre for Biodiversity; Países BajosFil: Fang, Zong Jie. Chinese Academy of Sciences; República de ChinaFil: Gardner, Ronald N.. No especifica;Fil: Gavrilova, Vera A.. Russian Geological Research Institute; RusiaFil: Goncharova, Irina A.. Russian Academy of Sciences; RusiaFil: Harries, Peter J.. University of South Florida; Estados UnidosFil: Hartman, Joseph H.. University of North Dakota; Estados UnidosFil: Hautmann, Michael. Paläontologisches Institut und Museum; SuizaFil: Hoeh, Walter R.. Kent State University; Estados UnidosFil: Hylleberg, Jorgen. Institute of Biology; DinamarcaFil: Jiang, Bao Yu. Nanjing University; República de ChinaFil: Johnston, Paul. Mount Royal University; CanadáFil: Kirkendale, Lisa. University Of Wollongong; AustraliaFil: Kleemann, Karl. Universidad de Viena; AustriaFil: Koppka, Jens. Office de la Culture. Section d’Archéologie et Paléontologie; SuizaFil: Kříž, Jiří. Czech Geological Survey. Department of Sedimentary Formations. Lower Palaeozoic Section; República ChecaFil: Machado, Deusana. Universidade Federal do Rio de Janeiro; BrasilFil: Malchus, Nikolaus. Institut Català de Paleontologia; EspañaFil: Márquez Aliaga, Ana. Universidad de Valencia; EspañaFil: Masse, Jean Pierre. Universite de Provence; FranciaFil: McRoberts, Christopher A.. State University of New York at Cortland. Department of Geology; Estados UnidosFil: Middelfart, Peter U.. Australian Museum; AustraliaFil: Mitchell, Simon. The University of the West Indies at Mona; JamaicaFil: Nevesskaja, Lidiya A.. Russian Academy of Sciences; RusiaFil: Özer, Sacit. Dokuz Eylül University; TurquíaFil: Pojeta, John Jr.. National Museum of Natural History; Estados UnidosFil: Polubotko, Inga V.. Russian Geological Research Institute; RusiaFil: Pons, Jose Maria. Universitat Autònoma de Barcelona; EspañaFil: Popov, Sergey. Russian Academy of Sciences; RusiaFil: Sanchez, Teresa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Sartori, André F.. Field Museum of National History; Estados UnidosFil: Scott, Robert W.. Precision Stratigraphy Associates; Estados UnidosFil: Sey, Irina I.. Russian Geological Research Institute; RusiaFil: Signorelli, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Silantiev, Vladimir V.. Kazan Federal University; RusiaFil: Skelton, Peter W.. Open University. Department of Earth and Environmental Sciences; Reino UnidoFil: Steuber, Thomas. The Petroleum Institute; Emiratos Arabes UnidosFil: Waterhouse, J. Bruce. No especifica;Fil: Wingard, G. Lynn. United States Geological Survey; Estados UnidosFil: Yancey, Thomas. Texas A&M University; Estados Unido