Potomacanthus lobatus gen. et sp. nov., a new flower of probable Lauraceae from the Early Cretaceous (Early to Middle Albian) of eastern North America

A charcoalified fossil flower, Potomacanthus lobatus gen. et sp. nov., is described from the Early Cretaceous (Early to Middle Albian) Puddledock locality, Virginia, USA. Internal floral structure was studied using nondestructive synchrotron-radiation x-ray tomographic microscopy (SRXTM). The flower is bisexual and trimerous. The perianth consists of two whorls of tepals. The androecium has two whorls of fertile stamens. Anthers open by two distally hinged valves. The gynoecium consists of a single carpel that is plicate in the style and ascidiate in the ovary and contains a single pendant ovule. The fossil flower shares many similarities with flowers of extant Lauraceae and is unlike flowers of other families of Laurales. However, the fossil flower also differs in detail from all extant or fossil Lauraceae, particularly in configuration of the androecium. The new taxon, together with previously described but more fragmentary material from the Puddledock locality, provides the earliest fossil record of plants more closely related to Lauraceae than to any other extant family. It reveals several derived morphological characters that are potential synapomorphies among extant representatives of the family Lauraceae and contributes to the growing evidence for an early diversification of Laurales before the end of the Early Cretaceous.     

Noradrenaline modulates transmission at a central synapse by a presynaptic mechanism

The lateral division of the central amygdala (CeAL) is the target of ascending fibers from the pain-responsive and stress-responsive nuclei in the brainstem. We show that single fiber inputs from the nociceptive pontine parabrachial nucleus onto CeAL neurons form suprathreshold glutamatergic synapses with multiple release sites. Noradrenaline, acting at presynaptic alpha2 receptors, potently inhibits this synapse. This inhibition results from a decrease in the number of active release sites with no change in release probability. Introduction of a presynaptic scavenger of Gbetagamma subunits blocked the effects of noradrenaline, and botulinum toxin A reduced its effects, showing a direct action of betagamma subunits on the release machinery. These data illustrate a mechanism of presynaptic modulation where the output of a large multiple-release-site synapse is potently regulated by endogenously released noradrenaline and suggests that the CeA may be a target for the central nociceptive actions of noradrenaline.     

Ecological niche breadth and microhabitat guild structure in temperate Australian reptiles: Implications for natural resource management in endangered grassy woodland ecosystems

Ecological theory predicts that species with narrow niche requirements (habitat specialists) are more vulnerable to anthropocentric disturbances than those with broad niche requirements (habitat generalists). Hence, understanding a species ecological niche and guild membership would serve as a valuable management tool for providing a priori assessments of a species extinction risk. It also would help to forecast a species capacity to respond to land use change, as what might be expected to occur under financial incentive schemes to improve threatened ecological vegetation communities. However, basic natural history information is lacking for many terrestrial species, particularly reptiles in temperate regions of the world. To overcome this limitation, we collated 3527 reptile observations from 52 species across an endangered woodland ecoregion in south‐eastern Australia and examined ecological niche breadth and microhabitat guild structure. We found 30% of species had low ecological niche values and were classified as habitat specialists associated with large eucalypt trees, woody debris, surface rock or rocky outcrops. Cluster analysis separated species into six broad guilds based on microhabitat similarity. Approximately 80% of species belonged to guilds associated with old growth vegetation attributes or non‐renewable litho‐resources such as surface rock or rocky outcrops. Our results suggest that agri‐environment schemes that focus purely on grazing management are unlikely to provide immediate benefits to broad suites of reptiles associated with old growth vegetation and litho‐resources. Our classification scheme will be useful for identifying reptile species that are potentially vulnerable to anthropocentric disturbances and may require alternative strategies for improving habitat suitability and reptile conservation outcomes in grassy woodland ecosystems.     

Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitors

Potent and orally bioavailable SCD inhibitors built on an azetidinyl pyridazine scaffold were identified. In a one-month gDIO mouse model of obesity, we demonstrated that there was no therapeutic index even at low doses; efficacy in preventing weight gain tracked closely with skin and eye adverse events. This was attributed to the local SCD inhibition in these tissues as a consequence of the broad tissue distribution observed in mice for this class of compounds. The search for new structural scaffolds which may display a different tissue distribution was initiated. In preparation for an HTS campaign, a radiolabeled azetidinyl pyridazine displaying low non-specific binding in the scintillation proximity assay was prepared.     

Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: from systemic to liver-targeting inhibitors

Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors.     

Protein organization in mouse liver peroxisomes.

Peroxisomes from mouse liver were fractionated with Triton X-114, a procedure which yields a detergent phase consisting of proteins containing hydrophobic binding sites, and a nondetergent, or aqueous, phase containing hydrophilic proteins. When this method was applied to peroxisomes from control mice, catalase and fatty acyl-CoA oxidase distributed to the aqueous phase, whereas the integral membrane protein, PMP68, and the bifunctional protein were recovered exclusively in the detergent phase. Urate oxidase distributed intermediate between these two phases. With peroxisomes from mice treated with the peroxisome proliferator clofibrate, the bifunctional protein was recovered in both the detergent and the aqueous phases, and urate oxidase was shifted toward the aqueous phase. Other analyses of the subperoxisomal distribution of the bifunctional protein were consistent with a proportion of this protein being tightly associated with the peroxisomal membrane, or with some other uncharacterized, poorly soluble, component. Sucrose gradient centrifugation of the aqueous phase resulting from Triton X-114 fractionation of peroxisomes revealed that a major proportion of catalase, fatty acyl-CoA oxidase, the bifunctional protein, and other unidentified proteins behaved as if associated under these conditions. In this respect, use of a higher concentration of Triton X-114 for peroxisome fractionation led to the partitioning of some catalase and fatty acyl-CoA oxidase to the detergent phase, indicating the presence of some detergent-accessible hydrophobic binding sites even on these proteins. These data have been interpreted as indicating matrix protein associations in vivo, associations which may be responsive to proliferator treatment.     

Composition of fatty acids triacylglycerols and unsaponifiable matter in Calophyllum calaba L. oil from Guadeloupe

The composition of the kernel oils of two Calophyllum species (Calophyllum calaba L. and Calophyllum inophyllum L.) was investigated. The physico-chemical properties and fatty acid composition of the kernel oils were examined. In two species, oleic acid C18:1 (39.1-50%) is the dominating fatty acid followed by linoleic acid C18:2 (21.7-31.1%) as the second major fatty acid. Stearic C18:0 (13.4-14.3%) and palmitic C16:0 (11-13.7%) acids are the major saturates. The oils contains an appreciable amount of unsaturated fatty acids (70.8-73.10%). Most of the fatty acids are present as triacylglycerol (76.7-84%), twenty one triacylglycerols are detected with predominantly unsaturated triacylglycerols. The total unsaponifiable content, its general composition and the identity of the components of the sterol and tocopherol fractions are presented. In both species, analysis of the unsaponifiable fractions revealed the preponderance of phytosterols, mainly stigmasterol (35.8-45.1%) and beta-sitosterol (41.1-43.1%). Among the eight tocopherols and tocotrienols present in two species, variations exist; alpha-tocopherol (183 mg/kg) is the main tocopherol in Calophyllum calaba L. and Delta-tocotrienol (236 mg/kg) is the dominant tocotrienol in Calophyllum inophyllum L.     

When Earth started blooming: insights from the fossil record

Recent palaeobotanical studies have greatly increased the quantity and quality of information available about the structure and relationships of Cretaceous angiosperms. Discoveries of extremely well preserved Cretaceous flowers have been especially informative and, combined with results from phylogenetic analyses of extant angiosperms (based mainly on molecular sequence data), have greatly clarified important aspects of early angiosperm diversification. Nevertheless, many questions still persist. The phylogenetic origin of the group itself remains as enigmatic as ever and, in some cases, newly introduced techniques from molecular biology have given confusing results. In particular, relationships between the five groups of extant seed plants remain uncertain, and it has sometimes proved difficult to reconcile estimates of the time of divergence between extant lineages made using a 'molecular clock' with the fossil record. One result, however, is becoming increasingly clear: a great deal of angiosperm diversity is extinct. Some groups of angiosperms were evidently more diverse in the past than they are today. In other cases, fossils defy assignment to extant groups at the family level or below. This raises the possibility that evolutionary conclusions based solely upon extant taxa that are merely relics of groups that were once much more diverse might be misled by the effects of extinction. It also introduces the possibility that some early enigmatic fossils might represent lineages that diverged from the main line of angiosperm evolution below the most recent common ancestor of all extant taxa. These, and other questions, are among those that need to be addressed by future palaeobotanical research.     

Changes in survival characteristics of Diplostomum spathaceum cercariae emerged from cadmium-exposed Lymnaea stagnalis

The effect of exposing Lymnaea stagnalis (Gastropoda: Pulmonata), infected with Diplostomum spathaceum (Trematoda: Diplostomatidae), to 100 microg l(-1) cadmium for 7 days on survival characteristics (survival, tail loss, decaudized cercarial life-span) of emerged cercariae was investigated. Exposure of L. stagnalis to cadmium resulted in significantly increased D. spathaceum cercarial survival and an inhibited tail loss compared to controls. The normal parallel relationship which exists over time between decreasing cercarial survival and increasing tail loss in controls was changed in cercariae from cadmium-exposed hosts with an increased proportion of cercarial deaths occurring without tail loss. The decaudized cercarial life-span over the survival period of the cercarial population did not significantly change. However comparisons between individuals decaudized during the initial 24 h time period with those which were decaudized during the final period of cercarial survival showed a significantly altered life span which did not occur in the control population. As a potential indicator of penetration 'fitness' comparisons were also undertaken between control and exposed cercariae decaudized during the initial 24 h time period, which revealed that the decaudized cercarial life-span from the exposed hosts was significantly different from controls. This may have important implications for the ability of cercariae to migrate through the tissues of their target host. The importance and relevance of these results to parasite transmission are discussed.