Epithelial-mesenchymal transition (EMT), the conversion between rigid epithelial cells and motile mesenchymal cells, is a reversible cellular process involved in tumorigenesis, metastasis, and chemoresistance. Numerous studies have found that several types of tumor cells show a high degree of cell-to-cell heterogeneity in terms of their gene expression signatures and cellular phenotypes related to EMT. Recently, the prevalence and importance of partial or intermediate EMT states have been reported. It is unclear, however, whether there is a general pattern of cancer cell distribution in terms of the overall expression of epithelial-related genes and mesenchymal-related genes, and how this distribution is related to EMT process in normal cells. In this study, we performed integrative transcriptomic analysis that combines cancer cell transcriptomes, time course data of EMT in non-tumorigenic epithelial cells, and epithelial cells with perturbations of key EMT factors. Our statistical analysis shows that cancer cells are widely distributed in the EMT spectrum, and the majority of these cells can be described by an EMT path that connects the epithelial and the mesenchymal states via a hybrid expression region in which both epithelial genes and mesenchymal genes are highly expressed overall. We found that key patterns of this EMT path are observed in EMT progression in non-tumorigenic cells and that transcription factor ZEB1 plays a key role in defining this EMT path via diverse gene regulatory circuits connecting to epithelial genes. We performed Gene Set Variation Analysis to show that the cancer cells at hybrid EMT states also possess hybrid cellular phenotypes with both high migratory and high proliferative potentials. Our results reveal critical patterns of cancer cells in the EMT spectrum and their relationship to the EMT process in normal cells, and provide insights into the mechanistic basis of cancer cell heterogeneity and plasticity.

ABSTRACT:Surveillance is critical for identifying and monitoring pathogen activity in wildlife populations, but often is cost-and time-prohibitive and logistically challenging. We tested the hypothesis that wildlife rehabilitation centers are useful for monitoring pathogen activity using West Nile virus (WNV) as a case study. We hypothesized that birds submitted to wildlife rehabilitation centers would have a similar prevalence of antibody to WNV as free-ranging birds. From 2008 to 2010, we collected sera from peridomestic birds submitted to the Wildlife Care Clinic (WCC), a wildlife rehabilitation center in central Iowa, and tested them for antibodies to WNV. We also collected and tested sera from free-ranging peridomestic birds in the area from which approximately 50% of WCC submissions historically originated. Prevalences of WNV antibodies in free-ranging birds and in peridomestic WCC birds were 2.3% (44/1,936) and 2.8% (2/72), respectively. However, none of the birds submitted to the WCC from the area where we captured free-ranging birds had antibodies (0/29). Our results indicate that rehabilitation facilities are not likely to be useful for monitoring WNV activity at small spatial scales or over short-time periods due to the low endemic prevalence of WNV, and low and variable submission rates. However, at larger spatial scales (ca. nine Iowa counties) WNV antibody prevalence in peridomestic birds submitted to the WCC was similar to that of free-ranging birds. Although limitations to using rehabilitation birds to monitor WNV must be considered, testing these birds could be useful for monitoring WNV activity regionally, especially with many states limiting surveillance due to budgetary constraints.

In the Plains states of the central United States, research suggests that the prevalence of West Nile virus (WNV) disease in humans is higher in agricultural areas than in nonagricultural areas. In contrast, there is limited information about WNV exposure in birds, the primary amplifying host of WNV, in agriculturally dominated landscapes. We evaluated whether exposure to WNV in peridomestic birds sampled in central Iowa varied with the proportion of land use devoted to agriculture. Over the summers of 2009 and 2010, we captured birds in sites comprising gradients of agricultural, urban, and natural land uses, and tested their sera for antibodies to WNV. Overall, WNV antibody prevalence was low (2.3%). Our results suggest that agricultural land use had minimal influence on WNV exposure in birds. We conclude that birds are not likely to be useful indicators of WNV activity in agricultural areas in the Plains states despite human risk being highest in those areas. Antibody prevalence for WNV, however, was higher in American Robins, Mourning Doves, and Northern Cardinals than in other species, making these species potentially useful for monitoring WNV activity in the US Plains states.

Little is known about the frequency, occurrence, or impacts of West Nile virus (WNV) on many Iowa wildlife species, including birds. The lack of knowledge about WNV in Iowa bird populations is partially due to difficulties associated with monitoring wildlife health. We evaluated the utility of wildlife rehabilitation centers for providing information about wildlife population health and disease monitoring, as well as assessing where on the central Iowa landscape birds have the highest risk of exposure to WNV. Specifically, we: 1) examined the records of two ecologically important groups of birds (raptors [orders Accipritiformes, Falconiformes, and Strigiformes] and corvids [family Corvidae]) submitted over a ten year period to the Wildlife Care Clinic (WCC), a rehabilitation facility in central Iowa, and analyzed whether there was significant variation in submission rates and diagnoses among years, seasons, and species, 2) sampled peridomestic birds submitted to the WCC as well as free-living peridomestic birds within the geographic area from which most of the WCC"s submissions originated, and compared WNV prevalence between these groups, and 3) collected blood samples from free-living birds captured at central Iowa sites comprising gradients of urban, agriculture, and natural land uses, and tested them for exposure to WNV. Our results indicated that submission rates and diagnoses to the WCC varied among years, season, and species. In most cases, records were not of sufficient detail to draw specific Daszak, P, A.A. Cunningham, and A.D. Hyatt. 2000. Emerging infectious diseases of wildlifethreats to biodiversity and human health. Science 287:443-449.

Complete Citation: Tehan, Gerald and Fallon, Anthony Bruce and Randall, Natalie (1997). The effect of item and relational processing on incidental long-term memory for order. Memory, 5 (4), Accessed from USQ ePrints http://eprints