The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. Overall design: mRNA profiles of whole Drosophila melanogaster adult males from an African, American, Asian and European population after infection with Beauveria bassiana. Samples include uninfected controls, 8h after infection and 24h after infection. 3 biological replicates each (2 in the case of American controls).
Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.
Sex, Specimen part, Subject
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Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part, Compound
View SamplesSmall molecule inhibitors of JAK kinases have shown clinical effcacy in the treatment of certain autoimmune diseases. While these are known to block upstream JAK signalling events, their broader impact on the transcriptional footprint in immunocytes are unknown. Here we explore the effects of pan- and isoform-specific JAK blockade on the immuno-genomic network by genomic profiling.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part, Compound
View SamplesB cells respond robustly to type 1 interferons which signal through JAK1 and TYK2. Here we analyzed the effects of a panel of JAK inhibitors on the IFNa transcriptional response in activated B cells in vitro.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part
View SamplesIL2 signals are transmitted through JAK1 and JAK3, but the transcriptomic consequences of each to the overall response is unclear. Here we analyzed the relative contribution of JAK1 and JAK3 to the NK cell IL2 response in vitro using titrated doses of isoform specific JAK inhibitors. Blockade of JAK1 and JAK3 have unequal effects on IL2-induced transcripts at pharmacologically relevant doses.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part
View SamplesCD4+ T cells respond robustly to type 1 interferons which signal through JAK1 and TYK2. Here we analyzed the effects of a panel of JAK inhibitors on the IFNa transcriptional response in activated CD4+ T cells in vitro.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part
View SamplesHere we analyzed the transcriptional response to IL2 in NK cells in vitro.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part
View SamplesHere we analyzed thetranscriptional response to IFNa in activated B cells in vitro. We found robust induction of ISGs as early as 2hrs.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part
View SamplesHere we analyzed the transcriptional response to IFNa in activated CD4+ T cells in vitro. We found robust induction of ISGs as early as 2hrs.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part
View SamplesMales are 50% more likely to develop end stage kidney failure compared to women. In this study we wanted to find out the molecular mechanism responsible for this increased risk. We collected kidney samples from patients with and without kidney disease and performed a comprehensive gene expression analysis in healthy and diseased male and female kidneys.
Human and murine kidneys show gender- and species-specific gene expression differences in response to injury.
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