ZNF224 is a transcriptional repressor of AXL in chronic myeloid leukemia cells.

ZNF224 is a KRAB-zinc finger transcription factor that exerts a key tumor suppressive role in chronic myelogenous leukemia. In this study, we identify the receptor tyrosine kinase Axl as a novel target of ZNF224 transcriptional repression activity. Axl overexpression is found in many types of cancer and is frequently associated with drug resistance. Interestingly, we also found that sensitivity to imatinib can be partly restored in imatinib-resistant chronic myelogenous leukemia cells by ZNF224 overexpression and the resulting suppression of Axl expression. These results, in accordance with our previous findings, support the role of ZNF224 in imatinib responsiveness and shed new insights into potential therapeutic use of ZNF224 in imatinib-resistant chronic myelogenous leukemia.

Contribution of deltaic wetland food sources to coastal macrobenthic consumers (Po River Delta, north Adriatic Sea).

Estuaries are known to export huge quantities of terrigenous/riverine organic matter and nutrients to coastal areas, subsidizing food sources to their communities; however, this process is seldom investigated in complex multichannel delta-prodelta systems. Stable isotope analysis was used to investigate the contribution of organic sources originated from the Po River Delta, one of the widest deltaic wetlands in the northern Mediterranean Sea, to the diet of the nearby coastal macrobenthic consumers, and their influence on invertebrates' trophic structure and biomass. Following intense river flood events, macrofauna samples were collected in the prodelta area at increasing distance from the main river distributary mouth. Potential primary resources were collected within the delta and the prodelta areas. A terrestrial signal in the primary consumers' diet was evident as a shift in their δ13C, being this more 13C depleted near the main river distributary. The Bayesian mixing models indicated an important contribution of deltaic sources, in particular C4-grass detritus (25-57%), to primary consumers' diet, confirming a strong energetic link between delta and prodelta areas. Overall, most of the consumers' biomass were concentrated at sites close to the main distributary mouth, mainly as suspension and surface deposit feeders. A simplification of the macrobenthic community structure, accompanied by narrower transfer pathways was also evident at sites more distant from the main river distributary, in relation to changes in the quality of resources. Our data, although limited to winter season, suggest that during periods of low in situ productivity but high river flow energy, invertebrates are able to efficiently exploit terrigenous food sources, restraining the detrimental effect of increased turbidity and sedimentation. We conclude that riparian/wetland vegetation associated with river deltas can provide important food sources to marine primary consumers. These results furthermore highlight the need for integrated management and protection strategies of connected land-sea ecosystems.

Role of ZNF224 in c-Myc repression and imatinib responsiveness in chronic myeloid leukemia.

The transcription factor ZNF224 plays a key proapoptotic role in chronic myelogenous leukemia (CML), by modulating Wilms Tumor protein 1 (WT1) dependent apoptotic genes transcription. Recently, we demonstrated that Bcr-Abl signaling represses ZNF224 expression in Bcr-Abl positive CML cell lines and in CML patients. Interestingly, Imatinib and second-generation tyrosine kinase inhibitors specifically increase ZNF224 expression. On the other hand, Bcr-Abl positively modulates, via JAK2 activation, the expression of the c-Myc oncogene, which is required for Bcr-Abl oncogenic transformation in CML. Consequently, JAK2 inhibitors represent promising molecular therapeutic tools in CML. In this work, we demonstrate that ZNF224 is a novel transcriptional repressor of c-Myc in CML. We also show that ZNF224 induction by Imatinib and AG490, a specific JAK2 inhibitor, is responsible for the transcriptional repression of c-MYC, thus highlighting the crucial role of the ZNF224/c-Myc axis in Imatinib responsiveness. Interestingly, we also report that ZNF224 is induced by AG490 in Imatinib-resistant CML cells, leading to c-Myc repression and apoptosis induction. These findings suggest that the development of molecular tools able to induce ZNF224 expression could provide promising means to bypass Imatinib resistance in CML.

Diversity and Distribution of Prokaryotes within a Shallow-Water Pockmark Field.

Pockmarks are crater-like depression on the seafloor associated with hydrocarbon ascent through muddy sediments in continental shelves around the world. In this study, we examine the diversity and distribution of benthic microbial communities at shallow-water pockmarks adjacent to the Middle Adriatic Ridge. We integrate microbial diversity data with characterization of local hydrocarbons concentrations and sediment geochemistry. Our results suggest these pockmarks are enriched in sedimentary hydrocarbons, and host a microbial community dominated by Bacteria, even in deeper sediment layers. Pockmark sediments showed higher prokaryotic abundance and biomass than surrounding sediments, potentially due to the increased availability of organic matter and higher concentrations of hydrocarbons linked to pockmark activity. Prokaryotic diversity analyses showed that the microbial communities of these shallow-water pockmarks are unique, and comprised phylotypes associated with the cycling of sulfur and nitrate compounds, as well as numerous know hydrocarbon degraders. Altogether, this study suggests that shallow-water pockmark habitats enhance the diversity of the benthic prokaryotic biosphere by providing specialized environmental niches.

Food web of a confined and anthropogenically affected coastal basin (the Mar Piccolo of Taranto) revealed by carbon and nitrogen stable isotopes analyses.

Carbon and nitrogen stable isotope analysis was used to examine the food web of the Mar Piccolo of Taranto, a coastal basin experiencing several anthropogenic impacts. Main food sources (algal detritus, seaweeds, particulate organic matter (POM) and sediment organic matter (SOM)) and benthic and pelagic consumers were collected during two contrasting seasons (June and April), at four sites distributed over two inlets, and characterized by different level of confinements, anthropogenic inputs and the presence of mussels farming. δ(13)C values of organic sources revealed an important contribution of POM to both planktonic and benthic pathways, as well as the influence of terrigenous inputs within both inlets, probably due to high seasonal land runoff. Although δ(13)C of both sources and consumers varied little between sampling sites and dates, δ(15)N spatial variability was higher and clearly reflected the organic enrichment in the second inlet as well as the uptake of anthropogenically derived material by benthic consumers. On the other hand, within the first inlet, the isotopic composition of consumers did not change in response to chemical contamination. However, the impact of polluted sediments near the Navy Arsenal in the first inlet was detectable at the level of the macrobenthic trophic structure, showing high dominance of motile, upper level consumers capable to face transient conditions and the reduction of the more resident deposit feeders. We therefore underline the great potential of matching stable isotope analysis with quantitative studies of community structure to assess the effects of multiple anthropogenic stressors.