Functional conservation of the fruitless male sex-determination gene across 250 Myr of insect evolution

Male sexual behavior in the fruit fly Drosophila melanogaster is regulated by fruitless (fru), a sex-determination gene specifying the synthesis of BTB-Zn finger proteins that likely function as male-specific transcriptional regulators. Expression of fru in the nervous system specifies male sexual behavior and the muscle of Lawrence (MOL), an abdominal muscle that develops in males but not in females. We have isolated the fru ortholog from the malaria mosquito Anopheles gambiae and show the gene's conserved genomic structure. We demonstrate that male-specific mosquito fru protein isoforms arise by conserved mechanisms of sex-specifically activated and alternative exon splicing. A male-determining function of mosquito fru is revealed by ectopic expression of the male mosquito isoform FRUMC in fruit flies; this results in MOL development in both fru-mutant males and fru+ females who otherwise develop no MOL. In parallel, we provide evidence of a unique feature of muscle differentiation within the fifth abdominal segment of male mosquitoes that strongly resembles the fruit fly MOL. Given these conserved features within the context of 250 Myr of evolutionary divergence between Drosophila and Anopheles, we hypothesize that fru is the prototypic gene of male sexual behavior among dipteran insects

Biomarkers and Predictors of Restorative Therapy Effects After Stroke

Many restorative therapies that promote brain repair are under development. Stroke is very heterogeneous, highlighting the need to identify target populations and to understand inter-subject differences in treatment response. Several neuroimaging measures have shown promise as biomarkers and predictors, including measures of structure and function, in gray matter and white matter. Choice of biomarker and predictor can vary with the content of therapy and with the population under study, for example, contralesional hemisphere measures may be of particular importance in patients with more severe injury. Studies of training effects in healthy subjects provide insights useful to brain repair. Limitations of published studies include a focus on chronic stroke, however the brain is most galvanized to respond to restorative therapies in the early days post-stroke. Multimodal approaches might be the most robust approach for stratifying patients and so for optimizing prescription of restorative therapies after stroke