The lower Mississippian Ballagan Formation of northern Britain is one of only two successions worldwide to yield the earliest known tetrapods with terrestrial capability following the end-Devonian mass extinction event. Studies of the sedimentary environments and habitats in which these beasts lived have been an integral part of a major research project into how, why and under what circumstances this profound step in the evolution of life on Earth occurred. Here, a new palaeogeographic map is constructed from outcrop data integrated with new and archived borehole material. The map shows the extent of a very low-relief coastal wetland developed along the tropical southern continental margin of Laurussia. Coastal floodplains in the Midland Valley and Tweed basins were separated from the marginal marine seaway of the Northumberland–Solway Basin to the south by an archipelago of more elevated areas. A complex mosaic of sedimentary environments was juxtaposed, and included fresh and brackish to saline and hypersaline lakes, a diverse suite of floodplain palaeosols and a persistent fluvial system in the east of the region. The strongly seasonal climate led to the formation of evaporite deposits alternating with flooding events, both meteoric and marine. Storm surges drove marine floods from the SW into both the western Midland Valley and Northumberland–Solway Basin; marine water also flooded into the Tweed Basin and Tayside in the east. The Ballagan Formation is a rare example in the geological record of a tropical, seasonal coastal wetland that contains abundant, small-scale evaporite deposits. The diverse sedimentary environments and palaeosol types indicate a network of different terrestrial and aquatic habitats in which the tetrapods lived.

1 Neuromuscular blocking drugs (NMBD's) are known to produce cardiovascular side e ects manifesting as brady/tachycardias. In this study we have examined the interaction of a range of steroidal NMBD's with recombinant human m1 ± m5 muscarinic receptors expressed in Chinese hamster ovary cells. Our main hypothesis is that NMBD's may interact with m2 (cardiac) muscarinic receptors. 2 All binding studies were performed with cell membranes prepared from CHO m1 ± m5 cells in 1 ml volumes of 20 mM HEPES, 1 mM MgCl 2 at pH 7.4 for 1 h. Muscarinic receptors were labelled with [ 3 H]-NMS and displacement studies were performed with pancuronium, vecuronium, pipecuronium, rocuronium and gallamine. In addition a range of muscarinic receptor subtype selective reference compounds were included. In order to determine the nature of any interaction the e ects of pancuronium, rocuronium and vecuronium on methacholine inhibition of forskolin stimulated cyclic AMP formation in CHO m2 cells was examined. Cyclic AMP formation was assessed in whole cells using a radioreceptor assay. All data are mean+s.e.mean (n55). 50 ) by pirenzepine in CHO m1 membranes (7.97+0.04), methoctramine in CHO m2 membranes (8.55+0.1), 4-diphenylacetoxy-Nmethyl piperidine methiodide (4-DAMP) in CHO m3 membranes (9.38+0.03), tropicamide in CHO m4 membranes (6.98+0.01). 4-DAMP, pirenzepine, tropicamide and methoctramine displaced [ 3 H]NMS in CHO m5 membranes with pK 50 values of 9.20+0.14, 6.59+0.04, 6.89+0.05 and 7.22+0.01 respectively. These data con®rm homogenous subtype expression in CHO m1 ± m5 cells. 5 [ 3 H]NMS binding was displaced dose-dependently (pK 50 ) by pancuronium (m1, 6.43+0.12; m2, 7.68+0.02; m3, 6.53+0.06; m4, 6.56+0.03; m5, 5.79+0.10), vecuronium (m1, 6.14+0.04; m2, 6.90+0.05; m3, 6.17+0.04; m4, 7.31+0.02; m5, 6.20+0.07), pipecuronium (m1, 6.34+0.11; m2, 6.58+0.03; m3, 5.94+0.01; m4, 6.60+0.06; m5, 4.80+0.03), rocuronium (m1, 5.42+0.01; m2, 5.40+0.02; m3, 4.34+0.02; m4, 5.02+0.04; m5, 5.10+0.03) and gallamine (m1, 6.83+0.05; m2, 7.67+0.04; m3, 6.06+0.06; m4, 6.20+0.03; m5, 5.34+0.03). 6 Cyclic AMP formation was inhibited dose dependently by methacholine in CHO m2 cells pEC 50 for control and pancuronium (300 nM) treated cells were 6.18+0.34 and 3.57+0.36 respectively. Methacholine dose-response curves in the absence and presence of rocuronium (1 mM) and vecuronium (1 mM) did not di er signi®cantly. Pancuronium, vecuronium and rocuronium did not inhibit cyclic AMP formation alone indicating no agonist activity. 7 With the exception of rocuronium there was a signi®cant interaction with m2 muscarinic receptors with all NMBD's at clinically achievable concentrations suggesting that the brady/tachycardias associated with these agents may result from an interaction with cardiac muscarinic receptors. Furthermore pancuronium at clinically achievable concentrations antagonised methacholine inhibition of cyclic AMP formation in CHO m2 cells further suggesting that the tachycardia produced by this agent results from muscarinic antagonism. The mech...

Chondrichthyan teeth from a new locality in the Scottish Borders supply additional evidence of Early Carboniferous chondrichthyans in the UK. The interbedded dolostones and siltstones of the Ballagan Formation exposed along Whitrope Burn are interpreted as representing a restricted lagoonal environment that received significant amounts of land-derived sediment. This site is palynologically dated to the latest Tournaisian–early Viséan. The diverse dental fauna documented here is dominated by large crushing holocephalan toothplates, with very few, small non-crushing chondrichthyan teeth. Two new taxa are named and described. Our samples are consistent with worldwide evidence that chondrichthyan crushing faunas are common following the Hangenberg extinction event. The lagoonal habitat represented by Whitrope Burn may represent a temporary refugium that was host to a near-relict fauna dominated by large holocephalan chondrichthyans with crushing dentitions. Many of these had already become scarce in other localities by the Viséan and become extinct later in the Carboniferous. This fauna provides evidence of early endemism or niche separation within European chondrichthyan faunas at this time. This evidence points to a complex picture in which the diversity of durophagous chondrichthyans is controlled by narrow spatial shifts in niche availability over time.

A conglomerate bed from the Tournaisian Ballagan Formation of Scotland preserves a rich array of vertebrate and other non-marine fossils providing an insight into the wider ecosystem and palaeoenvironment that existed during this pivotal stage of Earth history. It challenges hypotheses of a long-lasting post-extinction trough following the end-Devonian extinction event. The fauna recovered includes a wide size range of tetrapods, rhizodonts and dipnoans, from tiny juveniles or small-bodied taxa up to large adults, and more than one taxon of each group is likely. Some fauna, such as actinopterygians and chondrichthyans, are rare as macrofauna but are better represented in the microfossil assemblage. The fauna provides evidence of the largest Carboniferous lungfish ever found.The specimens are preserved in a localised, poorly-sorted conglomerate which was deposited in the deepest part of a river channel, the youngest of a group of channels. In 24The fauna recovered includes a wide size range of tetrapods, rhizodonts and dipnoans, 25 from tiny juveniles or small-bodied taxa up to large adults, and more than one taxon of each 26 group is likely. Some fauna, such as actinopterygians and chondrichthyans, are rare as 27 macrofauna but are better represented in the microfossil assemblage. The fauna provides 28 evidence of the largest Carboniferous lungfish ever found. 29The specimens are preserved in a localised, poorly-sorted conglomerate which was 30 deposited in the deepest part of a river channel, the youngest of a group of channels. In addition 31 to the fossils (micro-and macro-), the conglomerate includes locally-derived clasts of palaeosols 32 and other distinctive elements of the surrounding floodplains. Charcoal fragments represent stem 33 and possible trunk tissue from arborescent pteridosperms. Preservation of the fossils indicates 34 some aerial exposure prior to transport, with abrasion from rolling. 35The findings presented here contrast with other published trends in vertebrate size that 36 are used to interpret a reduction in maximum sizes during the Tournaisian. The richness of the 37 fauna runs counter to the assumption of a depauperate non-marine fauna following the end-38 Devonian Hangenberg event, and charcoal content highlights the occurrence of fire, with the 39 requisite levels of atmospheric oxygen during that stage.40 41