POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation.

To investigate the relevance of adrenocorticotrophic hormone (ACTH) therapy in human gouty arthritis, we have tested the effect of several ACTH-related peptides in a murine model of experimental gout. Systemic treatment of mice with ACTH4-10 (MEHFRWG) (10-200 microgram s. c.) inhibited neutrophil accumulation without altering peripheral blood cell counts or circulating corticosterone levels. A similar effect was seen with alpha- and beta-melanocyte stimulating hormones (1-30 microgram s.c.). In vivo release of the chemokine KC-(detected in the lavage fluids before maximal influx of neutrophils) was significantly reduced (-50 to -60%) by ACTH4-10. Macrophage activation in vitro, determined as phagocytosis and KC release, was inhibited by ACTH and ACTH4-10 with approximate IC50 values of 30 nM and 100 microM, respectively. The melanocortin receptor type 3/4 antagonist SHU9119 prevented the inhibitory actions of ACTH4-10 both in vitro and in vivo. However, melanocortin type 3, but not type 4, receptor mRNA was detected in mouse peritoneal macrophages by RT-PCR. Therefore, we propose that activation of this receptor type by ACTH4-10 and related amino acid sequences attenuates KC release (and possibly production of other cytokines) from macrophages with consequent inhibition of the host inflammatory response, thus providing a notional anti-inflammatory mechanism for ACTH that is unrelated to stimulation of glucocorticoid release.     

The relationship between surface sediment diatom assemblages and pH in 33 Galloway lakes: Some regression models for reconstructing pH and their application to sediment cores

The species composition of surface sediment diatom assemblages in 33 Galloway lakes, pH range c. 4.5 to 7.4, is related in a statistically significant manner to water acidity (or to factors closely associated with pH). Predictive models of summer mean pH, using simple regression equations of Index B (Renberg & Hellberg, 1982) with both Scandinavian and Galloway data sets, and multiple regression equations using diatom pH preference groups and individual species, are described and applied to fossil diatoms in six sediment cores. Although multiple regression of individual species gives the highest correlation coefficient (r²=0.87) in the modern data set this method is least appropriate for reconstructing pH values from fossil material where predictor species are often absent. Of the four methods examined here it is suggested that multiple regression of diatom preference groups is probably the most suitable for pH reconstructions from sediment cores.     

Matching diatom assemblages in lake sediment cores and modern surface sediment samples: the implications for lake conservation and restoration with special reference to acidified systems

Restoration goals for damaged freshwater habitats can bedefinedaccording to ecological as well as to chemical criteria. Fordisturbed lakes, the sediment microfossil record can be usedtoselect potential modern analogue sites as possible restorationtarget ecosystems.Fossil diatom assemblages in two acidified lakes (Round LochofGlenhead and Loch Dee) in Galloway, Scotland, were comparedfloristically with modern surface sediment samples from ca. 200lakes in Britain, Ireland, Sweden and Norway using numericaltechniques. Mean squared Chi-squared dissimilarity (SCD)valuesbased on between sample Chi-square distance measures were usedtocompare samples.Space-for-time substitution using diatom assemblage matchingtechniques identified several modern analogue sites withHebrideanLoch Teanga and Irish Lough Claggan possessing modern diatomflorasmost similar to those which existed at the Round Loch ofGlenheadand Loch Dee before acidification.From the point of view of atmospheric pollution, the mostcloselymatching modern analogue sites were not necessarily in themostpristine regions. Some analogues occurred in UK regions ofmoderateor low acid deposition and modern diatom assemblages inatmospherically cleaner mid Norway were generally less similarfloristically.It is argued that identification of modern analogue sitesraisesthe possibility of using time-space substitution of closelymatchedmodern and fossil samples to infer whole lake ecosystems.Diatoms are however poor indicators of some water chemistryvariables and the two closest matched modern analogue siteshavetoo high calcium concentrations making faunistic comparisonsquestionable.Identification of good modern analogue lakes can be improvedbyusing selection criteria, other than diatoms, to pre-selectsites.Screening inappropriate sites according to water chemistry andbasin features combined with a larger biological database ofmodernand fossil samples offers a promising way of refining theselectionprocesses.Despite necessary refinements, modern analogue matching canpotentially identify whole lake ecosystems that can serve asbiological target communities for currently disturbed sites.Beingbased on biological rather than chemical criteria, thisapproachdoes not rely on species-water chemistry transfer functions.It istherefore directly relevant to lake conservation andrestorationobjectives and offers an alternative method for reconstructing lakepalaeo-environments.     

Multiple molecular recognition properties of the lipocalin protein family

The lipocalins, a diverse family of small extracellular ligand proteins, display a remarkable range of different molecular properties. While their binding of small hydrophobic molecules, and to a lesser extent their binding to cell surface receptors, is well known, it is shown here that formation of macromolecular complexes is also a common feature of this family. Analysis of known crystallographic structures reveals that the lipocalins process a conserved common structure: an antiparallel β-barrel with a repeated +1 topology. Comparisons show that within this overall similarity the structure of individual proteins is specifically adapted to bind their particular ligands, forming a binding site from an internal cavity (within the barrel) and/or an external loop scaffold, which gives rise to different binding modes that reflects the need to accommodate ligands of different shape, size, and chemical structure. The architecture of the lipocalin fold suggests that the both the ends and sides of this barrel are topologically distinct, differences also apparent in analyses of structural and sequence variation within the family. These different can be linked to experimental evidence suggesting a possible functional dichotomy between the two ends of the lipocalin fold. The structurally invariant end of the molecule may be implicated in general binding small ligands and forming macromolecular complexes via an exposed binding surface.     

Influence of soil gas contamination on tree root growth

Summary Rooted-cuttings and saplings of green ash (Fraxinus lanceolata) and hybrid poplar (Populus spp) were planted on a former municipal refuse landfill and on a nearby nonlandfill control plot. The root systems of four trees of each species and size were excavated on the landfill plot-two growing in an area where the concentrations of anaerobic landfill gases were relatively high and two in a relatively low-gas area. Two trees of each species and size were also excavated on the control. The root systems of both species were significantly shallower on the landfill plot than on the control. Green ash appeared to avoid the adverse gas environment of the deeper soil layers on the landfill by producing adventitious roots. Hybrid poplar became adapted in a different manner, by redirecting root growth from the deepter soil layers to the soil surface.