Selective inhibitors of cardiac ADPR cyclase as novel anti-arrhythmic compounds

ADP-ribosyl cyclases (ADPRCs) catalyse the conversion of nicotinamide adenine dinucleotide to cyclic adenosine diphosphoribose (cADPR) which is a second messenger involved in Ca2+ mobilisation from intracellular stores. Via its interaction with the ryanodine receptor Ca2+ channel in the heart, cADPR may exert arrhythmogenic activity. To test this hypothesis, we have studied the effect of novel cardiac ADPRC inhibitors in vitro and in vivo in models of ventricular arrhythmias. Using a high-throughput screening approach on cardiac sarcoplasmic reticulum membranes isolated from pig and rat and nicotinamide hypoxanthine dinuleotide as a surrogate substrate, we have identified potent and selective inhibitors of an intracellular, membrane-bound cardiac ADPRC that are different from the two known mammalian ADPRCs, CD38 and CD157/Bst1. We show that two structurally distinct cardiac ADPRC inhibitors, SAN2589 and SAN4825, prevent the formation of spontaneous action potentials in guinea pig papillary muscle in vitro and that compound SAN4825 is active in vivo in delaying ventricular fibrillation and cardiac arrest in a guinea pig model of Ca2+ overload-induced arrhythmia. Inhibition of cardiac ADPRC prevents Ca2+ overload-induced spontaneous depolarizations and ventricular fibrillation and may thus provide a novel therapeutic principle for the treatment of cardiac arrhythmias

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

A Ceratopsian Dinosaur from the Lower Cretaceous of Western North America, and the Biogeography of Neoceratopsia

Competing interests: Andrew A. Farke has read the journal's policy and the authors of this manuscript have the following competing interests: Andrew A. Farke is a volunteer section editor and academic editor for PLOS ONE. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.Acknowledgments It is a pleasure to offer our most heartfelt thanks to Scott K. Madsen, who found OMNH 34557 and prepared it with consummate skill. We are grateful to James Taylor, Jack Owen, the Keebler family, and the Montana Bureau of Land Management for access to outcrops of the Cloverly Formation. We thank Xu Xing (IVPP) and Hai-Lu You (formerly CAGS-IG) for facilitating access to specimens, Mark Loewen, Joseph Frederickson, Darren Naish, and Leonardo Maiorino for productive discussion and comments, and Roger Burkhalter for assistance in photography. Gary Wisser, from the scientific visualization center at Western University of Health Sciences, is gratefully acknowledged for the high resolution scan of the cranium. Reviews by Peter Makovicky, Hai-Lu You, and editor Peter Wilf improved the manuscript.Author Contributions Conceived and designed the experiments: AAF WDM RLC. Performed the experiments: AAF WDM RLC. Analyzed the data: AAF WDM RLC MJW. Contributed reagents/materials/analysis tools: AAF WDM RLC MJW. Wrote the paper: AAF WDM RLC MJW.The fossil record for neoceratopsian (horned) dinosaurs in the Lower Cretaceous of North America primarily comprises isolated teeth and postcrania of limited taxonomic resolution, hampering previous efforts to reconstruct the early evolution of this group in North America. An associated cranium and lower jaw from the Cloverly Formation (?middle–late Albian, between 104 and 109 million years old) of southern Montana is designated as the holotype for Aquilops americanus gen. et sp. nov. Aquilops americanus is distinguished by several autapomorphies, including a strongly hooked rostral bone with a midline boss and an elongate and sharply pointed antorbital fossa. The skull in the only known specimen is comparatively small, measuring 84 mm between the tips of the rostral and jugal. The taxon is interpreted as a basal neoceratopsian closely related to Early Cretaceous Asian taxa, such as Liaoceratops and Auroraceratops. Biogeographically, A. americanus probably originated via a dispersal from Asia into North America; the exact route of this dispersal is ambiguous, although a Beringian rather than European route seems more likely in light of the absence of ceratopsians in the Early Cretaceous of Europe. Other amniote clades show similar biogeographic patterns, supporting an intercontinental migratory event between Asia and North America during the late Early Cretaceous. The temporal and geographic distribution of Upper Cretaceous neoceratopsians (leptoceratopsids and ceratopsoids) suggests at least intermittent connections between North America and Asia through the early Late Cretaceous, likely followed by an interval of isolation and finally reconnection during the latest Cretaceous.Funding was received from the National Science Foundation (DEB 9401094, 9870173, http://www.nsf.gov); National Geographic Society (5918-97, http://www.nationalgeographic.com/); and American Chemical Society (PRF #38572-AC8, http://www.acs.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Yeshttp://www.plosone.org/static/editorial#pee

ZURICH: Palaeontological Museum of the University of Zurich

The Palaeontological Museum of the University of Zurich is part of the Palaeontologica Instiut and Museum. It was founded in 1956, but palaeontological objects were already prepared and exhibited before in the Zoologica Museum of the University of Zurich. Teh roots of ur collections date much further back to the eighteenth century: Many of the fossil specimens published by Scheuchzer between 1731 and 1735 are stored in our collections (Fig. 56.1), and some specimens are even on display. These specimens were later incorporated in the "Vereingte Zürcher Naturhistorische Sammlung" of the Zürcher Naturforschende Gesellschaft, which was founded in 1745 by Johann Gessner. After a time interval of administrative dubieties, geological objects and fossil invertebrates were distributed to the geological collections while vertebrate fossils became par of the Zoological collections around 1909

Coastal sediments from the Algarve: low-latitude climate archive for the Aptian-Albian

The Late Aptian to Early Albian transition has previously been identified as a possible example of substantial climate cooling within the mid-Cretaceous greenhouse period. To study the response of continental weathering and terrestrial vegetation to this cooling episode at low- to mid-latitudes, marine nearshore deposits from the Algarve Basin (SW Portugal) have been investigated with a combined approach including palynology, clay mineralogy and bulk-rock geochemistry. In the Lower Aptian part of the succession, quartz-rich sandstone facies is accompanied by high abundances of early diagenetic kaolinite, which is interpreted to reflect episodes of enhanced humidity and high meteoric flow-through. In contrast, the Late Aptian to Early Albian deposits are characterized by high abundances of detrital clay minerals (mica and chlorite) indicating the dominance of physical weathering processes in the source area, most probably related to low precipitation rates in conjunction with tectonically enhanced erosion. Palynological data show a strong dominance of Classopollis pollen associated with low pteridophyte spore abundances, suggesting warm semi-arid to arid palaeoenvironments. Changes in sedimentation patterns from varicoloured lagoonal marls to thick-bedded shallow-water carbonates are neither expressed in the spore-pollen assemblages nor in the distributions of clay minerals which both remain essentially stable throughout the Late Aptian to Early Albian. These relatively stable patterns are in contrast with various lines of evidence, predominantly from high-latitude areas, that suggest a significant cooling during this time interval. Our study demonstrates that terrestrial environments of low- to mid-latitude regions were not significantly affected by the Late Aptian - Early Albian ‘‘cold snap’’

Palynology of Triassic–Jurassic boundary sections in northern Switzerland

A first palynostratigraphic scheme of Upper Triassic deposits in northern Switzerland was established based on spore-pollen associations and dinoflagellate cyst records from the upper part of the Upper Triassic Klettgau Formation and the lower part of the Lower Jurassic Staffelegg Formation. Drill cores from the Adlerberg region (Basel Tabular Jura) and from Weiach (northern part of Canton Zurich) as well as from an outcrop at the Chilchzimmersattel (Basel Folded Jura) were studied and five informal palynological associations are distinguished. These palynological associations correlate with palynological association of the Central European Epicontinental Basin and the Tethyan realm and provide a stratigraphic framework for the uppermost Triassic sediments in northern Switzerland. Throughout the uppermost Triassic to Jurassic palynological succession a remarkable prominence of Classopollis spp. is observed. Besides Classopollis spp. the three Rhaetian palynological associations A to C from the Upper Triassic Belchen Member include typical Rhaetian spore-pollen and dinoflagellate taxa (e.g., Rhaetipollis germanicus, Geopollis zwolinskae, Rhaetogonyaulax rhaetica, and Dapcodinium priscum). Association B differs from association A in a higher relative abundance of the sporomorph taxa Perinopollenites spp. and the consistent occurrence of Granuloperculatipollis rudis and Ricciisporites tuberculatus. Spore diversity is highest in the late Rhaetian palynological association C and includes Polypodiisporites polymicroforatus. A Rhaetian age for the Belchen Member is confirmed by palynological associations A–C, but there is no record of the latest Rhaetian and the earliest Jurassic. In contrast to the Rhaetian palynological associations the Early Jurassic associations W and D include Pinuspollenites spp., Trachysporites fuscus (in association W), and Ischyosporites variegatus. In the view of the end-Triassic mass extinction and contemporaneous environmental changes the described palynofloral succession represents the pre-extinction phase (associations A and B) including a distinct transgression, the extinction phase (association C) associated with a regression, and the post-extinction phase (association W)