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.     

Toxicity of cadmium and zinc mixtures to the decaudized cercarial life span of Diplostomum spathaceum

The effects of cadmium and zinc mixtures at concentrations ranging from 0.1 to 10,000 microg l(-1) on the life-span of decaudized cercarial bodies (cercariae that have shed their tails) of Diplostomum spathaceum (Trematoda: Diplostomatidae) was investigated. Cercariae were exposed to metal mixtures of equal and unequal concentrations, and a low-dose pre-treatment followed by a high-dose exposure mixtures. Metal mixtures demonstrated variable effects on decaudized cercariae either by increasing or reducing their life-span compared to single metal exposures dependent on concentration and the type of mixed metal treatment. Prolonged exposure to equal metal mixtures at low concentrations (0.1-100 microg l(-1)) resulted in a reduction in the life-span of decaudized cercariae at 0.1 and 100 microg l(-1) in those individuals decaudized during the initial 24 h exposure period compared with those decaudized during the final 24 h period of cercarial survival, whilst in controls there was no significant life-span change between the two time periods. Decaudized cercariae which were exposed to low concentrations (0.1-100 microg l(-1)) of equal metal mixtures were also evaluated for their role as an indicator of larval 'fitness' for migrating through the tissues of their target fish host for those individuals decaudized during the initial 24 h exposure period, and demonstrated only a limited change in their life-span compared to control and single metal exposures. The importance of metal mixtures in parasite establishment in the fish host is discussed.     

A synthetic TLR4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease

Current evidence indicates that the chronic inflammation observed in the intestines of patients with inflammatory bowel disease is due to an aberrant immune response to enteric flora. We have developed a lipid A-mimetic, CRX-526, which has antagonistic activity for TLR4 and can block the interaction of LPS with the immune system. CRX-526 can prevent the expression of proinflammatory genes stimulated by LPS in vitro. This antagonist activity of CRX-526 is directly related to its structure, particularly secondary fatty acyl chain length. In vivo, CRX-526 treatment blocks the ability of LPS to induce TNF-alpha release. Importantly, treatment with CRX-526 inhibits the development of moderate-to-severe disease in two mouse models of colonic inflammation: the dextran sodium sulfate model and multidrug resistance gene 1a-deficient mice. By blocking the interaction between enteric bacteria and the innate immune system, CRX-526 may be an effective therapeutic molecule for inflammatory bowel disease.     

Differentiation to the CCR2+ inflammatory phenotype in vivo is a constitutive, time-limited property of blood monocytes and is independent of local inflammatory mediators

It is proposed that CCR2+ monocytes are specifically recruited to inflammatory sites, whereas CCR2- monocytes are recruited to normal tissue to become resident macrophages. Whether these subsets represent separate lineages, how differential trafficking is regulated and whether monocytes undergo further differentiation is uncertain. Using a mouse model of autoimmune uveoretinitis we examined monocyte trafficking to the inflamed retina in vivo. We show that bone marrow-derived CD11b+ F4/80- monocytes require 24 to 48 h within the circulation and lymphoid system before acquiring the CCR2+ phenotype and trafficking to the inflamed retina is enabled. This phenotype, and the capacity to traffic were lost by 72 h. Monocyte CCR2 expression followed a similar time course in normal mice indicating that differentiation to an inflammatory phenotype is a constitutive, time-limited property, independent of local inflammatory mediators. Phenotypic analysis of adoptively transferred cells indicated that circulating inflammatory monocytes also differentiate into CD11c+ and B220+ dendritic cells and F4/80+ tissue macrophages in vivo. Our data supports the hypothesis of continuous extravasation and progressive differentiation over time of inflammatory monocytes in the circulation rather than replication within the actively inflamed tissue, and supports the concept of myeloid dendritic cell differentiation from trafficking monocytes under physiological conditions in vivo.     

Subunit exchange by CheA histidine kinases from the mesophile Escherichia coli and the thermophile Thermotoga maritima

Dimerization of the chemotaxis histidine kinase CheA is required for intersubunit autophosphorylation [Swanson, R. V., Bourret, R. B., and Simon, M. I. (1993) Mol. Microbiol. 8, 435-441]. Here we show that CheA dimers exchange subunits by the rate-limiting dissociation of a central four-helix bundle association domain (P3), despite the high stability of P3 versus unfolding. P3 alone determines the stability and exchange properties of the CheA dimer. For CheA proteins from the mesophile Escherichia coli and the thermophile Thermotoga maritima, subunit dissociation activates at temperatures where the respective organisms live (37 and 80 degrees C). Under destabilizing conditions, P3 dimer dissociation is cooperative with unfolding. Chemical denaturation is reversible for both EP3 and TP3. Aggregation accompanies thermal unfolding for both proteins under most conditions, but thermal unfolding is reversible and two-state for EP3 at low protein concentrations. Residue differences within interhelical loops may account for the contrasted thermodynamic properties of structurally similar EP3 and TP3 (41% sequence identity). Under stabilizing conditions, greater correlation between activation energy for dimer dissociation and P3 stability suggests more unfolding in the dissociation of EP3 than TP3. Furthermore, destabilization of extended conformations by glycerol slows relative dissociation rates more for EP3 than for TP3. Nevertheless, at physiological temperatures, neither protein likely unfolds completely during subunit exchange. EP3 and TP3 will not exchange subunits with each other. The receptor coupling protein CheW reduces the subunit dissociation rate of the T. maritima CheA dimer by interacting with the regulatory domain P5.     

Influence of cadmium exposure on the incidence of first intermediate host encystment by Echinoparyphium recurvatum cercariae in Lymnaea peregra

The effect of cadmium exposure of the snail first intermediate host Lymnaea peregra on the incidence of encystment of Echinoparyphium recurvatum (Digenea: Echinostomatidae) cercariae without emergence from the snail was investigated. Exposure to 100 microg l(-1) Cd for 72 h caused a significant increase in the incidence of first host encystment when compared to controls. In addition, autometallographic staining of E. recurvatum daughter rediae and developing cercariae showed that there was metal accumulation within their body tissues. The significance of these findings to parasite transmission in metal-polluted environments is discussed.