Seasonal inundations shape the floodplain characteristics of the Pantanal, a large wetland in Central South America. In the first study combining stable carbon and nitrogen isotope analysis with classical stomach content analysis in this region, we investigated the influence of the annual inundation on diet and isotopic composition of floodplain fish. Apart from potential food items, 33 fish species from the Coqueiro Lake were analyzed, 10 of which were present during both the wet and dry season 1999. A d 13 C and d 15 N plot of the floodplain ecosystem allowed us to assess a foodchain of 3 -4 trophic levels. However, the wide overlap of nitrogen values suggested that the organisms act on trophic continua rather than on distinct levels. The foodweb was based mainly on C 3 -plant carbon. However, fish species capable of feeding on terrestrial invertebrates (e. g., Brycon microlepis) had d 13 C values above -25 ‰, indicating 13 -30 % intake of C 4 -plant based carbon during the flooding period. The novel use of vector coordinates and 2-dimensional ANOVA showed that the seasonal isotopic shifts of d 13 C and d 15 N were highly significant for some feeding guilds. d 15 N values increased from the wet to dry season in most Aquatic Sciences fish species, and these shifts were highly significant for omnivores (Astyanax bimaculatus, Triportheus nematurus, Tetragonopterus argenteus and Moenkhausia dichroura), and significant for invertivores (Gymnogeophagus balzanii and Poptella paraguayensis) and carnivores (Serrasalmus spilopleura). Average carbon isotope ratios decreased at the same time in the herbivores (Methynnis mola: 3.4 ‰) and detritivores (Psectrogaster curviventris: 5.3‰), but they did not change in the hypostomatic herbivore Sturisoma robustum. We explain these shifts by abundant and variable food sources during the inundation period and increasing carnivory and starvation during the dry season when the lake is confined to its central basin. Isotopic shifts between seasons were more prominent in less specialized species of omnivores, invertivores and some carnivores, whereas more specialized herbivores and detritivores appeared to be more influenced by changes in the carbon isotope ratio of the diet affected by biogeochemical processes such as respiration and methanogenesis. A general model for the interpretation of isotope data of floodplain fish considering different timescales is given.

Pancreatic ductal adenocarcinoma is the eighth most common cancer with the lowest overall 5-year relative survival rate of any tumor type today. Expression profiling using microarrays has been widely used to identify genes associated with pancreatic cancer development. To extract maximum value from the available gene expression data, we applied a meta-analysis to search for commonly differentially expressed genes in pancreatic ductal adenocarcinoma. We obtained data sets from four different gene expression studies on pancreatic cancer. We selected a consensus set of 2984 genes measured in all four studies and applied a meta-analysis approach to evaluate the combined data. Of the genes identified as differentially expressed, several were validated using RT-PCR and immunohistochemistry. Additionally, we used a class discovery algorithm to identify a gene expression signature. Our meta-analysis revealed that the pancreatic cancer gene expression data sets shared a significant number of up-and downregulated genes, independent of the technology used. This interstudy crossvalidation approach generated a set of 568 genes that were consistently and significantly dysregulated in pancreatic cancer. Of these, 364 (64.1%) were upregulated and 204 (35.9%) were downregulated in pancreatic cancer. Only 127 (22%) were described in the published individual analyses. Functional annotation of the genes revealed that genes presumably associated with the cell adhesionmediated drug resistance pathway are frequently overexpressed in pancreatic cancer. Meta-analysis is an important tool for the identification and validation of differentially expressed genes. These could represent good candidates for novel diagnostic and therapeutic approaches to pancreatic cancer.

Sepsis is a common and serious health problem whereby improvements in diagnosis are crucial in increasing survival rates. To test whether profiling transcription is applicable to sepsis diagnosis, we analyzed whole blood using a microarray containing probes for 340 genes relevant to inflammation. The patient's gene expression pattern was highly homogenous, resulting in 69% of differentially expressed genes. With a positive predictive value of 98%, a list of 50 differentially expressed genes was compiled, and randomly chosen transcripts were confirmed by PCR. Here, we present the first evidence that microarrays can identify typical gene expression profiles in the blood of patients with severe sepsis. Regardless of the heterogeneity of the patients, we observed a striking correlation between the conventional diagnostic classification and our approach. The unity of responses suggests that the principle of this multiparameter approach can be adapted to early stage sepsis diagnosis.

Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F. The induction of NL did not further increase drug binding but led to altered F due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

diameter) per treatment. The tubes were then placed in a water bath with a temperature gradient from top to bottom of 20 to 10 °C. We used a spectrophometric assay procedure 10 to establish the TMA concentration in 10 litres of the medium that had previously contained four fish (ides, Leuciscus idus, 10 cm long), and recorded the resulting vertical migration behaviour of daphnids exposed to this medium. TMA concentration in this 'fish' water was between 10 and 25 ȖM.We found that even low concentrations of TMA induce Daphnia to migrate to deeper waters during the day in our test system. At night, they migrate back to the surface when exposed to small amounts of TMA, and stay near the bottom when TMA levels are high (more than 100 ȖM). When the lowest TMA concentration that induces vertical migration is compared with the activity in the fish water, it is clear that the reaction of Daphnia to fish water is stronger than just to TMA alone. This indicates that, although TMA is an active component of the 'fish factor', it is likely to be part of a cocktail of substances that deter Daphnia. The other substances probably help to reduce the chemical threshold that induces migration. It is not clear whether the TMA concentrations used in this study represent realistic values for aquatic systems, as we could find no published details of TMA concentrations in aquatic systems.It has been shown 9 that the fish kairomone is broken down by bacteria. We therefore compared the average day depth of daphnids exposed to 75 ȖM TMA in autoclaved water, and with the antibiotic ampicillin added and the TMA dissolved in non-autoclaved lake water. The migration activity of the Daphnia in non-sterile water slowly decreased over time (Fig. 2). After 72 hours, the average day depth of the animals in non-sterile conditions was no longer significantly different from the average day depth of animals in sterile control medium.To investigate whether simply adding any substance to the water induces vertical migration, we added the same amount of TMAO and triethylamine to sterile water (both at 75 ȖM). As with the control Daphnia, there was no significant increase in day depth. We therefore conclude that the reaction to TMA is a specific one, and not simply a response to a change in conductivity or ionic strength of the medium.