FUS-DDIT3 Prevents the Development of Adipocytic Precursors in Liposarcoma by Repressing PPARγ and C/EBPα and Activating eIF4E

Background

FUS-DDIT3 is a chimeric protein generated by the most common chromosomal translocation t(12;16)(q13;p11) linked to liposarcomas, which are characterized by the accumulation of early adipocytic precursors. Current studies indicate that FUS-DDIT3- liposarcoma develops from uncommitted progenitors. However, the precise mechanism whereby FUS-DDIT3 contributes to the differentiation arrest remains to be elucidated.

Methodology/Principal Findings

Here we have characterized the adipocyte regulatory protein network in liposarcomas of FUS-DITT3 transgenic mice and showed that PPARγ2 and C/EBPα expression was altered. Consistent with in vivo data, FUS-DDIT3 MEFs and human liposarcoma cell lines showed a similar downregulation of both PPARγ2 and C/EBPα expression. Complementation studies with PPARγ but not C/EBPα rescued the differentiation block in committed adipocytic precursors expressing FUS-DDIT3. Our results further show that FUS-DDIT3 interferes with the control of initiation of translation by upregulation of the eukaryotic translation initiation factors eIF2 and eIF4E both in FUS-DDIT3 mice and human liposarcomas cell lines, explaining the shift towards the truncated p30 isoform of C/EBPα in liposarcomas. Suppression of the FUS-DDIT3 transgene did rescue this adipocyte differentiation block. Moreover, eIF4E was also strongly upregulated in normal adipose tissue of FUS-DDIT3 transgenic mice, suggesting that overexpression of eIF4E may be a primary event in the initiation of liposarcomas. Reporter assays showed FUS-DDIT3 is involved in the upregulation of eIF4E in liposarcomas and that both domains of the fusion protein are required for affecting eIF4E expression.

Conclusions/Significance

Taken together, this study provides evidence of the molecular mechanisms involve in the disruption of normal adipocyte differentiation program in liposarcoma harbouring the chimeric gene FUS-DDIT3.     

Spatial structure of the caddisfly (Insecta,Trichoptera) communities in a river basin in NW Spain affected by coal mining

The changes in caddisfly community structure and composition in the Sil River basin (NW Spain), associated with a gradient in natural conditions and a succession of alterations induced by human activity (mainly urban wastes and coal mining), were studied. Twenty-nine Trichoptera taxa belonging to 11 families were collected. The community diversity analysis showed important spatial differences from source to mouth. Towns and, above all, coal mines produced an increase in sulphate and chloride concentrations and conductivity, which adversely affected the trichopteran assemblages. A stepwise regression model, which introduced sulphate and chloride as variables, explained the changes in diversity produced in the basin (r=0.837, p< 0.01). The lowest diversity and richness values were recorded in the rivers suffering the greatest impact from coal mining or urban wastes. The heterogeneity values of the communities for the main rivers were clearly different. The greatest community heterogeneity corresponded to the main axis of the basin and was explained by spatial variability in water chemical composition. No relation was detected between structural changes at spatial level and geographical distance, such that pollution processes basically controlled the dynamics of the Trichoptera communities. Partial-CCA using distance from the source as a covariable revealed alkalinity and urban and mining-derived pollution as the main factors influencing caddisfly distribution. However, an ordination of sites in relation to the corresponding vectors did not fully agree with the chemical characteristics of the water. The species composition of the Trichoptera communities, therefore, did not seem to be good indicators of the chemical features of the rivers. The structure of the community (as expressed by richness and the Shannon index) appeared to be the better indicator of pollution.     

A 2-year experimental study on nutrient and predator influences on food web constituents in a shallow lake of north-west Spain

1. A 2‐year study was carried out on the roles of nutrients and fish in determining the plankton communities of a shallow lake in north‐west Spain. Outcomes were different each year depending on the initial conditions, especially of macrophyte biomass. In 1998 estimated initial ‘per cent water volume inhabited’ (PVI) by submerged macrophytes was about 35%. Phytoplankton biomass estimated as chlorophyll a was strongly controlled by fish, whereas effects of nutrient enrichment were not significant. In 1999 estimated PVI was 80%, no fish effect was observed on phytoplankton biomass, but nutrients had significant effects. Water temperatures were higher in 1998 than in 1999. 2. In the 1998 experiment, cladoceran populations were controlled by fish and cyanobacteria were the dominant phytoplankton group. There were no differences between effects of low (4 g fresh mass m^?2) and high (20 g fresh mass m^?2) fish density on total zooplankton biomass, but zooplankton biomass was higher in the absence of fish. With the high plant density in 1999, fish failed to control any group of the zooplankton community. 3. Total biovolume of phytoplankton strongly decreased with increased nutrient concentrations in 1998, although chlorophyll a concentrations did not significantly change. At higher nutrient concentrations, flagellate algae became more abundant with likely growth rates that could have overcompensated cladoceran feeding rates. This change in phytoplankton community composition may have been because of increases in the DIN : SRP ratio. Both chlorophyll a concentration and total phytoplankton biovolume increased significantly with nutrients in the 1999 experiment. 4. A strong decline of submerged macrophytes was observed in both years as nutrients increased, resulting in shading by periphyton. This shading effect could account for the plant decline despite lower water turbidity at the very high nutrient levels in 1998.     

Oncogenic potential of EAG K(+) channels.

We have investigated the possible implication of the cell cycle-regulated K(+) channel ether à go-go (EAG) in cell proliferation and transformation. We show that transfection of EAG into mammalian cells confers a transformed phenotype. In addition, human EAG mRNA is detected in several somatic cancer cell lines, despite being preferentially expressed in brain among normal tissues. Inhibition of EAG expression in several of these cancer cell lines causes a significant reduction of cell proliferation. Moreover, the expression of EAG favours tumour progression when transfected cells are injected into immune-depressed mice. These data provide evidence for the oncogenic potential of EAG.     

Perkinsoide chabelardi n. gen., a protozoan parasite with an intermediate evolutionary position: possible cause of the decrease of sardine fisheries?

Phenotypic scrutiny on the life cycle of Icthyodinium chabelardi (Perkinsoide chabelardi n. gen.) based on ultrastructural techniques, and molecular phylogenetic analysis of RNA gene sequences, were carried out in order to elucidate the taxonomic position of this parasite. The absence of plastid, presence of trichocysts, and chromosomes or chromatin condensed and low in number, suggested that this protozoan could be considered a dinoflagellate syndinial parasite. However, the life cycle, schizogonic divisions and structure of schizonts inside the host, the nuclei without the typical dinoflagellate appearance, presence of rhoptrias-like structures, a possible pseudo-conoid, and the biflagellated spore, resembled those of the genus Perkinsus. Phylogenetic analysis of genes transcribing for the RNA forming the small subunit and the large subunit suggests that this parasite has an ambiguous evolutionary position within the group formed by dinoflagellates, perkinsids and syndinials. Because of differences with dinoflagellates and similarities with perkinsids, we propose to change the generic name to P. chabelardi n. gen. High stationary infection prevalence on Sardina pilchardus eggs was observed. This protozoan parasite caused the death of all the infected sardine eggs, and therefore a high impact in the recruitment of this fishery in the Atlantic coast is expected.     

Current Status and Future Prospects for the Assessment of Marine and Coastal Ecosystem Services: A Systematic Review

Background

Research on ecosystem services has grown exponentially during the last decade. Most of the studies have focused on assessing and mapping terrestrial ecosystem services highlighting a knowledge gap on marine and coastal ecosystem services (MCES) and an urgent need to assess them.

Methodology/Principal Findings

We reviewed and summarized existing scientific literature related to MCES with the aim of extracting and classifying indicators used to assess and map them. We found 145 papers that specifically assessed marine and coastal ecosystem services from which we extracted 476 indicators. Food provision, in particular fisheries, was the most extensively analyzed MCES while water purification and coastal protection were the most frequently studied regulating and maintenance services. Also recreation and tourism under the cultural services was relatively well assessed. We highlight knowledge gaps regarding the availability of indicators that measure the capacity, flow or benefit derived from each ecosystem service. The majority of the case studies was found in mangroves and coastal wetlands and was mainly concentrated in Europe and North America. Our systematic review highlighted the need of an improved ecosystem service classification for marine and coastal systems, which is herein proposed with definitions and links to previous classifications.

Conclusions/Significance

This review summarizes the state of available information related to ecosystem services associated with marine and coastal ecosystems. The cataloging of MCES indicators and the integrated classification of MCES provided in this paper establish a background that can facilitate the planning and integration of future assessments. The final goal is to establish a consistent structure and populate it with information able to support the implementation of biodiversity conservation policies.