Sex-specific traits that lead to the production of dimorphic gametes, sperm in males and eggs in females, are fundamental for sexual reproduction and accordingly widespread among animals. Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure, and as a result of adaptive evolution they often become divergent. Indeed out of hundreds of male or female fertility genes identified in diverse organisms, only a very small number of them are implicated specifically in reproduction in more than one lineage. Few genes have exhibited a sex-biased, reproductive-specific requirement beyond a given phylum, raising the question of whether any sex-specific gametogenesis factors could be conserved and whether gametogenesis might have evolved multiple times. Here we describe a metazoan origin of a conserved human reproductive protein, BOULE, and its prevalence from primitive basal metazoans to chordates. We found that BOULE homologs are present in the genomes of representative species of each of the major lineages of metazoans and exhibit reproductive-specific expression in all species examined, with a preponderance of male-biased expression. Examination of Boule evolution within insect and mammalian lineages revealed little evidence for accelerated evolution, unlike most reproductive genes. Instead, purifying selection was the major force behind Boule evolution. Furthermore, loss of function of mammalian Boule resulted in male-specific infertility and a global arrest of sperm development remarkably similar to the phenotype in an insect boule mutation. This work demonstrates the conservation of a reproductive protein throughout eumetazoa, its predominant testis-biased expression in diverse bilaterian species, and conservation of a male gametogenic requirement in mice. This shows an ancient gametogenesis requirement for Boule among Bilateria and supports a model of a common origin of spermatogenesis.

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Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to investigate the mechanisms of apoE isoform dependent modulation of susceptibility to memory impairment.

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ObjectiveThe use of robotic radical hysterectomy has greatly increased in the treatment of early stage cervical cancer. We sought to compare surgical and oncologic outcomes of women undergoing robotic radical hysterectomy compared to open radical hysterectomy.MethodsThe clinic-pathologic, treatment, and recurrence data were abstracted through an Institutional Review Board-approved protocol at 2 separate large tertiary care centers in Seattle, Swedish Medical Center and the University of Washington. Data were collected from 2001–2012. Comparisons between the robotic and open cohorts were made for complications, recurrence, progression-free survival (PFS), and overall survival (OS).ResultsIn the study period, 109 robotic radical hysterectomies were performed. These were compared to 202 open radical hysterectomies. The groups were comparable in terms of age and body mass index (BMI). Length of stay (LOS) was considerably shorter in the robotic group (42.7 vs. 112.6 hours, p<0.001) as was estimated blood loss (EBL; 105.9 vs. 482.6 mL, p<0.001). There were more complications in the open radical hysterectomy group, 23.4% vs. 9.2% in the robotic group (p=0.002). The recurrence rate was comparable between the groups (10.1% vs. 10.4%, p=0.730). In multivariate adjusted analysis, robotic surgery was not a statistically significant predictor of PFS (p=0.230) or OS (0.85).ConclusionOur study, one of the largest multi-institution cohorts of patients undergoing robotic radical hysterectomy, suggest robotic radical hysterectomy leads to comparable oncologic outcomes in the treatment of early stage cervical cancer with improved short-term surgical outcomes such as decreased LOS and EBL.