Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production

Cultured melanoma cells release soluble factors that influence immune responses. Screening of a cDNA library with anti-sera from a melanoma patient identified an immunoreactive plaque, which encoded heavy-chain ferritin (H-ferritin), Previous studies have drawn attention to the immunosuppressive effects of this molecule and prompted further studies on its biochemical and functional properties in human melanoma, These studies demonstrated, firstly, that H-ferritin appeared to be secreted by melanoma cells, as shown by immunoprecipitation of a 21.5 kDa band from supernatants. It was also detected in extracts of melanoma cells by Western blotting as 43 and 64 kDa dimers and trimers of the 21.5 kDa fraction. Secondly, flow-cytometric analysis of H- and light-chain ferritin (L-ferritin) expression on melanoma showed a wide variation in L-ferritin expression and consequently of the ratio of H- to L-ferritin expression. Suppression of mitogenic responses of lymphocytes to anti-CD3 showed a correlation with the ratio of H- to L-ferritin in the supernatants and was specific for H-ferritin, as shown by inhibition studies with a monoclonal antibody (MAb) against H-ferritin, Similar results were obtained with H- and L-ferritin from other sources. Suppression of mitogenic responses of lymphocytes to anti-CD3 by H-ferritin was inhibited using a MAb against IL-IO, which suggested that the immunosuppressive effect of H-ferritin was mediated by IL-IO, Assays of cytokine production from anti-CD3-stimulated lymphocytes showed that H-ferritin markedly increased production of IL-10 and IFN-gamma and had only slight effects on IL-2 and IL-4 production, Our results suggest that melanoma cells may be a major source of H-ferritin and that production of the latter may account for some of the immunosuppressive effects of melanoma, (C) 2001 Wiley-Liss. Inc.

Structure revision and assignment of absolute stereochemistry of a marine C-21 bisfuranoterpene

The C-21 bisfuranoterpene (-)-isotetradehydrofurospongin-1 (6), previously isolated from a Western Australian Spongia sp., has been reisolated from a specimen of Spirastrella papilosa collected during scientific trawling operations in the Great Australian Eight. A 2D NMR analysis of 6 has prompted reassignment of the published structure 5, while degradation and chiral HPLC analysis have allowed determination of the absolute stereochemistry.

Onnamide F: A new nematocide from a southern Australian marine sponge, Trachycladus laevispirulifer

A southern Australian marine sponge, Trachycladus laevispirulifer, has yielded a potent new nematocide with antifungal activity which has been identified as onnamide F (1). The structure for 1 was assigned by detailed spectroscopic analysis and chemical conversion to the methyl ester 2. Onnamide F contains a common structural motif previously described in a number of natural products exhibiting interesting pharmacological activities, including the insect chemical defense agent pederin (3), and the sponge metabolites the onnamides, mycalamides, and theopederins.

Mirabilin G: A new alkaloid from a southern Australian marine sponge, Clathria species

A Clathria sp. collected during scientific trawling operations in the Great Australian Bight, Australia, has yielded the new alkaloid mirabilin G (1). A structure was secured for 1 by detailed spectroscopic analysis and comparison to known marine alkaloids.

Phorbasin B and C: Novel diterpenes from a southern Australian marine sponge, Phorbas species

A southern Australian Phorbas sp. has yielded the novel diterpenes phorbasin B (2) and phorbasin C (3). Phorbasins B and C possess a hitherto unknown carbon skeleton, and their structures were assigned on the basis of detailed spectroscopic analyses.

Two new species of Neolebouria Gibson, 1976 (Digenea : Opecoelidae) from temperate marine fishes of Australia

Neolebouria moretonensis n. sp. is described from Gerres subfasciatus (Gerreidae) from Moreton Bay, south-east Queensland and N. lineatus n. sp. is described from Centroberyx lineatus (Berycidae) from off Rottnest Island, south-west Western Australia. C. lineatus represents a new host family and order (Beryciformes) for the genus. The two new species are distinguished within the genus by their entire, tandem to oblique testes and cirrus-sacs that do not extend into the hind-body, by being less than 1 mm in length, and by the position of the genital pore and the relative size of the forebody and post-testicular region. N. lineatus and N. moretonensis are very similar but are distinguished by their caeca which extend further posteriorly in N. moretonensis. There is no apparent pattern in the host-specificity of this genus.

The isolation and synthesis of novel nematocidal dithiocyanates from an Australian marine sponge, Oceanapia sp.

Bioassay-directed fractionation of the EtOH extract of an Oceanapia sp. collected off the northern Rottnest Shelf, Australia, has yielded three novel dithiocyanates, thiocyanatins A (1), B (2a), and C (2b). The structures were determined by detailed spectroscopic analysis and confirmed by total synthesis. In addition to featuring an unprecedented dithiocyanate functionality, thiocyanatins possess an unusual 1,16-difunctionalized n-hexadecane carbon skeleton and are revealed as a hitherto unknown class of nematocidal agents

Cervical screening: population-based comparisons between self-reported survey and registry-derived Pap test rates

Objective: To compare self-reported cervical screening rates, as recorded in the 1998 NSW Health Survey, with registry-based cervical screening rates for NSW for the same period; and to examine factors associated with over-estimates of cervical screening rates by self-report. Methods: Self-reported cervical screening data was extracted from the 1998 NSW Health Survey, biennial screening rates estimated and compared with biennial cervical screening rates for 1997-98, as recorded on the NSW Pap Test Register (PTR). Rates and differences were related to socio-demographic characteristics of the 17 Area Health Services of NSW. Results: According to the 1998 NSW Health Survey, 74% of women reported having a Pap test during the previous two years. The equivalent rate recorded on the NSW PTR for 1997-98 was 62% (p

Phoriospongin A and B: Two new nematocidal depsipeptides from the Australian marine sponges Phoriospongia sp and Callyspongia bilamellata

Bioassay-directed fractionation of two southern Australian sponges, Phoriospongia sp. and Callyspongia bilamellata, yielded two new nematocidal depsipeptides, identified as phoriospongins A (1) and B (2). The structures of the phoriospongins were determined by detailed spectroscopic analysis and comparison with the previously reported sponge depsipeptide cyclolithistide A (3), as well as ESIMS and HPLC analysis of acid hydrolysates. It is noteworthy that the unique and yet structurally related metabolites 1-3 are found in sponges spanning three taxonomic orders, Poescilosclerida, Haplosclerida, and Lithistida.

Equilibrating isomers: Bromoindoles and a seco-xanthine encountered during a study of nematocides from the southern Australian marine sponge Hymeniacidon sp.

Bioassay-directed fractionation of a Hymeniacidon sp. yielded as nematocidal agents the equilibrating E/Z bromoindole ethyl esters 1 and 2 and corresponding methyl esters 3 and 4. Also isolated for the first time as a natural product was an equilibrating mixture of seco-xanthine formamides, attributed the trivial name hymeniacidin (5). The structure for 5 was assigned on the basis of detailed spectroscopic analysis and total synthesis.

Sperm environment affects offspring quality in broadcast spawning marine invertebrates

The provisioning of offspring can have far-reaching consequences for later life in a wide range of organisms and generally this provisioning is thought to be under maternal influence or control. In experiments with a broadcast-spawning ascidian, we found that the size of offspring was determined by egg size and the abundance of sperm present during fertilization. Larger eggs were fertilized at low sperm concentrations, whilst smaller eggs were successfully fertilized at high sperm concentrations. These differences in fertilized egg size resulted in differences in the development rate, hatching success and mean size of the subsequent larvae. Our results suggest that, in contrast to females that reproduce by other mating systems, free-spawning mothers lack some control over the provisioning of offspring. Furthermore, because males can alter the sperm environment, they can exert paternal (non-genetic) control over key offspring characteristics.

Evolution of local recruitment and its consequences for marine populations

Advantages of dispersal on the scales that are possible in a long pelagic larval period are not apparent, even for benthic species. An alternative hypothesis is that wide dispersal may be an incidental byproduct of an ontogenetic migration from and then back to the parental habitat. Under this hypothesis, the water column is a better habitat than the bottom for early development. Because the parental area is often an especially favorable habitat for juveniles and adults, selection may even favor larval retention or larval return rather than dispersal. Where larval capabilities and currents permit, a high percentage of recruits may then be produced from local adults. Expected consequences of a high proportion of local recruitment are stronger links between stock and recruitment, greater vulnerability to recruitment overfishing and local modifications of habitat, greater local benefits from fishery reserves, and possibly more localized adaptation within populations. Export of some larvae is consistent with a high proportion of retained or returning larvae, could stabilize populations linked by larval exchange, and provide connectivity between marine reserves. Even a small amount of larval export could account for the greater gene flow, large ranges, and long evolutionary durations seen in species with long pelagic larval stages.

Sources of variation in larval quality for free-spawning marine invertebrates: Egg size and the local sperm environment

There has been growing interest in the effects of variation in larval quality on the post-larval performance of adult marine invertebrates. Variation in egg/larval size is an obvious source of variation in larval quality but sources of variation have received little attention. For broadcast spawners, larval size may vary according to the local sperm environment but the generality of this result is unclear. Here, we show that, for a solitary ascidian, a polychaete and an echinoid, larval size is affected by the concentration of sperm present during fertilization. Larvae that are produced at high sperm concentrations are smaller than larvae that are produced from eggs exposed to low sperm concentrations. We also show that for three ascidians and an asteroid, egg size increases with maternal body size. These differences in larval size are likely to affect larval and subsequent adult performance in the field. Given that sperm concentrations in the field can fluctuate widely, it is likely that larval quality in free-spawning marine invertebrates will also vary widely.

Late Quaternary Milankovitch-scale climatic change and variability and its impact on monsoonal Australasia

Four pollen and charcoal records derived from marine cores around the northern perimeter of Australia are examined to provide a regional picture of patterns, causes and impacts of climate change over the last 100-300 ka. The availability of radiocarbon dates and oxygen isotope records for the cores provides primary chronological control. Spectral analysis of components of these records demonstrates an overall importance of Milankovitch frequencies with clear glacial-interglacial cyclicity dominated by variation in precipitation. In addition, a number of pollen taxa, as well as charcoal particles, exhibit a 30 ka frequency that is considered, from its relationship with biomass burning and with results of past modelling, to reflect changes in the intensity of El Nino-Southern Oscillation (ENSO) variability. Pollen components of all records show a decline, frequently stepwise, in more fire-sensitive vegetation and its replacement with more fire-tolerant vegetation. There is some evidence that this trend is linked to an onset or general increase in ENSO activity and perhaps also to variation in monsoon activity dating from about 300 ka BP that was caused by changes to oceanic circulation within the Indonesian region. The trend may have accelerated within the last 45 ka due to burning by indigenous people. (C) 2003 Elsevier B.V. All rights reserved.