Project description:In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. Here we show that increasing juvenile hormone activity to induce summer-like reproductive development in fall migrants does not alter directional flight behavior or its time-compensated orientation, as monitored in a flight simulator. Reproductive summer butterflies, in contrast, uniformly fail to exhibit directional, oriented flight. To define molecular correlates of behavioral state, we used microarray analysis of 9417 unique cDNA sequences. Gene expression profiles reveal a suite of 40 genes whose differential expression in brain correlates with oriented flight behavior in individual migrants, independent of juvenile hormone activity, thereby separating molecularly fall migrants from summer butterflies. Intriguing genes that are differentially regulated include the clock gene vrille and the locomotion-relevant tyramine beta hydroxylase gene. In addition, several differentially regulated genes (37.5% of total) are not annotated, suggesting unique functions associated with oriented flight behavior. We also identified 23 juvenile hormone-dependent genes in brain, which separate reproductive from non-reproductive monarchs; genes involved in longevity, fatty acid metabolism, and innate immunity are upregulated in non-reproductive (juvenile-hormone deficient) migrants. The results link key behavioral traits with gene expression profiles in brain that differentiate migratory from summer butterflies and thus show that seasonal changes in genomic function help define the migratory state.

Project description:In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. Here we show that increasing juvenile hormone activity to induce summer-like reproductive development in fall migrants does not alter directional flight behavior or its time-compensated orientation, as monitored in a flight simulator. Reproductive summer butterflies, in contrast, uniformly fail to exhibit directional, oriented flight. To define molecular correlates of behavioral state, we used microarray analysis of 9417 unique cDNA sequences. Gene expression profiles reveal a suite of 40 genes whose differential expression in brain correlates with oriented flight behavior in individual migrants, independent of juvenile hormone activity, thereby separating molecularly fall migrants from summer butterflies. Intriguing genes that are differentially regulated include the clock gene vrille and the locomotion-relevant tyramine beta hydroxylase gene. In addition, several differentially regulated genes (37.5% of total) are not annotated, suggesting unique functions associated with oriented flight behavior. We also identified 23 juvenile hormone-dependent genes in brain, which separate reproductive from non-reproductive monarchs; genes involved in longevity, fatty acid metabolism, and innate immunity are upregulated in non-reproductive (juvenile-hormone deficient) migrants. The results link key behavioral traits with gene expression profiles in brain that differentiate migratory from summer butterflies and thus show that seasonal changes in genomic function help define the migratory state. A total of 40 monarch butterflies were used for the microarray analysis. Of the 40, 10 (5 male/5 female) were summer butterflies (Designated as S) and 30 were fall butterflies. The fall butterflies were further divided into three groups: 10 (5 male/5 female) were untreated (F); 10 (5 male/5 female) were treated with methoprene (M), which is a juvenile hormone analog and induces the development of reproductive organs in migrant butterflies; and 10 (5 male/5 female) were treated with vehicle only (V). We collected total brain RNA from each of the 40 butterflies. The brain RNAs were amplified and then used to probe a custom Nimblegen array that was designed to analyze the 9,417 unique cDNA sequences established in our published EST library (http://titan.biotec.uiuc.edu/cgi-bin/ESTWebsite/estima_start?seqSet=butterfly). Our main interest is to find genes involved in migration. This includes genes regulating oriented flight behavior of the butterfly and genes that regulate reproductive status. To identify these genes, we approached the microarray data in two ways. First, we identified the potential genes involved in oriented flight behavior using the following strategy. We compared the summer group to each of the three fall groups (untreated, methoprene-treated, and vehicle-treated) for males and for females, and looked for gene regulation patterns common among the three comparisons for each sex. Because the comparisons were done separately for males and females, and our behavioral data did not show significant sex differences in flight orientation, we focused on the common differentially regulated genes that were shared between males and females. Accordingly, we identified 40 cDNAs that were differentially regulated between summer butterflies and fall migrants, irrespective of sex. Second, we looked for the juvenile hormone-response genes. Again, we performed sex-specific statistical analyses, and compared the summer and the fall groups, and the methoprene-treated and vehicle-treated migrants. We then screened for shared genes between the two groups for each sex. We next examined cDNAs that were differentially regulated in both males and females, to determine juvenile hormone-regulated genes involved in more global processes (e.g., longevity and fatty acid metabolism) that would not be expected to be sex-specific. We identified 23 putative juvenile hormone-response genes that were common between males and females.

Project description:Background: Oral squamous cell carcinoma (OSCC) is a major world health problem with over 400,000 new cases diagnosed annually. Despite advances in surgery and chemo-radiotherapy, the 5 year survival has remained roughly constant at approximately 50% for several decades. The disease is characterized by both clinical and genetic heterogeneity, so elucidating the molecular basis of this heterogeneity would have significant clinical implications. It is well recognized that OSCCs from Asia that are associated with betel quid chewing are phenotypically distinct from those from the West that are predominantly caused by smoking/drinking, but the genetic basis of these differences are largely unknown. The aim of this study is to examine the most related genetic factors, carcinogenic related pathways, and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups. Methods: We have compared the gene expression profiles of OSCCs and normal oral mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene expression arrays. Results: The gene expression profiles of UK and Sri Lankan OSCC are similar in many respects to other oral cancer expression profiles reported in the literature and were mainly similar to each other. However, genes involved in tumor invasion, metastasis and recurrence were more obviously associated with UK tumors as opposed to those from Sri Lanka. Interestingly, Ingenuity Pathway Analysis (IPA) revealed a highly activated cell-mediated immune response in both Sri Lankan normal and tumor samples relative to UK cohorts, which may, in part, explain the less aggressive behavior of these betel quid-induced OSCCs. Conclusion: The development of OSCCs in both UK and Sri Lankan populations appears largely mediated by similar biological pathways despite the differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. However, IPA revealed a highly activated “Cell-mediated Immune Response” in Sri Lankan normal and tumor samples relative to UK cohorts. It seems likely, therefore, that any future attempts to personalize treatment for OSCC patients will need to be different in Western and Asian countries to reflect differences in gene expression and the immune status of the patients.

Dataset Information

Bangladeshi women living in UK: Buccal cell DNA methylation analysis

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