Almost all organismal function is controlled by pathways composed of interacting genetic components. The relationship between pathway structure and the evolution of individual pathway components is not completely understood. For the nematode Caenorhabditis elegans, chemosensory pathways regulate critical aspects of an individual's life history and development. To help understand how olfaction evolves in Caenorhabditis and to examine patterns of gene evolution within transduction pathways in general, we analyzed nucleotide variation within and between species across two well-characterized olfactory pathways, including regulatory genes controlling the fate of the cells in which the pathways are expressed. In agreement with previous studies, we found much higher levels of polymorphism within C. remanei than within the related species C. elegans and C. briggsae. There are significant differences in the rates of nucleotide evolution for genes across the two pathways but no particular association between evolutionary rate and gene position, suggesting that the evolution of functional pathways must be considered within the context of broader gene network structure. However, developmental regulatory genes show both higher levels of divergence and polymorphism than the structural genes of the pathway. These results show that, contrary to the emerging paradigm in the evolution of development, important structural changes can accumulate in transcription factors. T HE integration of evolutionary and developmentalgenetics into the discipline of evolutionary developmental biology has provided a powerful framework for understanding the evolution of form and pattern. The major paradigm emerging from evo-devo is the belief that most evolutionary change is generated by changes in gene regulation as opposed to protein structure (King and Wilson 1975;Jacob 1977;Duboule and Wilkins 1998;Carroll 2005). This regulatory hypothesis focuses most strongly on changes in cisregulatory regions of genes, rather than on the evolution of the regulatory genes (e.g., transcription factors) themselves. This is because it is presumed that changes in cis-elements will be localized to the gene of interest, whereas changes in trans-acting factors will tend to have broad pleiotropic effects. However, there are numerous examples of important evolutionary transitions mapping to protein coding differences within and between species ( Although evo-devo, because of its historic ties with embryology and paleontology, has been confined to morphological evolution, the evo-devo approach is being applied to understand a broader set of topics such as the evolution of sexual development ( Thus far, most examinations of the evolution of regulatory changes have focused on single genes. Yet genes exist within broad functional networks, the structure of which could potentially have profound effects on the rates of evolution of the individual components within the network (Hahn and Kern 2005). For example, within metabolic pathways, we might expect upstream

Background Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KT) is a serious complication and a significant risk factor for graft failure. However, there is no clear evidence of the effectiveness of pre-transplant treatment using plasmapheresis (PP) or rituximab in preventing post-operative FSGS recurrence after KT. Methods This single-center retrospective study included 99 adult patients with biopsy-proven primary FSGS who underwent KT between 2007 and 2018. The patients were divided into the pre-treatment group (N = 53, 53.5%) and no pre-treatment group (N = 46, 46.5%). In the pre-transplant group, prophylactic PP was administered before KT in patients undergoing living donor transplantation and the day after KT in those undergoing deceased donor transplantation. Results The rate of immediate post-operative recurrence was significantly higher in the no pre-treatment group (16 [34.8%]) than in the pre-treatment group (5 [9.4%]; P = 0.002). There were three cases of graft failure due to recurrent FSGS, all of which were in the no pre-treatment group. After adjusting for possible confounding factors, age (per 10-year increase; OR = 0.61, CI, 0.42–0.90; P = 0.012) and pre-transplant treatment (vs. no pre-transplant treatment; OR = 0.17, CI, 0.05–0.54; P = 0.003) were identified as significant factors associated with FSGS recurrence. The rate of death-censored graft survival was significantly superior in the pretransplant treatment group (P = 0.042). Conclusion Pre-transplant treatment with PP was associated with beneficial effects on preventing FSGS recurrence after KT.

Background Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KT) is a serious complication and a significant risk factor for graft failure. However, there is no clear evidence of the effectiveness of pre-transplant treatment using plasmapheresis (PP) or rituximab in preventing post-operative FSGS recurrence after KT. Methods This single-center retrospective study included 99 adult patients with biopsy-proven primary FSGS who underwent KT between 2007 and 2018. The patients were divided into the pre-treatment group (N = 53, 53.5%) and no pre-treatment group (N = 46, 46.5%). In the pre-transplant group, prophylactic PP was administered before KT in patients undergoing living donor transplantation and the day after KT in those undergoing deceased donor transplantation. Results The rate of immediate post-operative recurrence was significantly higher in the no pre-treatment group (16 [34.8%]) than in the pre-treatment group (5 [9.4%]; P = 0.002). There were three cases of graft failure due to recurrent FSGS, all of which were in the no pre-treatment group. After adjusting for possible confounding factors, age (per 10-year increase; OR = 0.61, CI, 0.42–0.90; P = 0.012) and pre-transplant treatment (vs. no pre-transplant treatment; OR = 0.17, CI, 0.05–0.54; P = 0.003) were identified as significant factors associated with FSGS recurrence. The rate of death-censored graft survival was significantly superior in the pretransplant treatment group (P = 0.042). Conclusions Pre-transplant treatment with PP was associated with beneficial effects on preventing FSGS recurrence after KT.