Unique Changes in Mitochondrial Genomes Associated with Reversions of S-Type Cytoplasmic Male Sterility in Maizemar

Cytoplasmic male sterility (CMS) in plants is usually associated with the expression of specific chimeric regions within rearranged mitochondrial genomes. Maize CMS-S plants express high amounts of a 1.6-kb mitochondrial RNA during microspore maturation, which is associated with the observed pollen abortion. This transcript carries two chimeric open reading frames, orf355 and orf77, both unique to CMS-S. CMS-S mitochondria also contain free linear DNA plasmids bearing terminal inverted repeats (TIRs). These TIRs recombine with TIR-homologous sequences that precede orf355/orf77 within the main mitochondrial genome to produce linear ends. Transcription of the 1.6-kb RNA is initiated from a promoter within the TIRs only when they are at linear ends. Reversions of CMS-S to fertility occur in certain nuclear backgrounds and are usually associated with loss of the S plasmids and/or the sterility-associated region. We describe an unusual set of independently recovered revertants from a single maternal lineage that retain both the S plasmids and an intact orf355/orf77 region but which do not produce the 1.6-kb RNA. A 7.3-kb inversion resulting from illegitmate recombination between 14-bp microrepeats has separated the genomic TIR sequences from the CMS-associated region. Although RNAs containing orf355/orf77 can still be detected in the revertants, they are not highly expressed during pollen development and they are no longer initiated from the TIR promoter at a protein-stabilized linear end. They appear instead to be co-transcribed with cytochrome oxidase subunit 2. The 7.3-kb inversion was not detected in CMS-S or in other fertile revertants. Therefore, this inversion appears to be a de novo mutation that has continued to sort out within a single maternal lineage, giving rise to fertile progeny in successive generations

Where are we with bladder preservation for muscle-invasive bladder cancer in 2017?

Introduction: In 2017, neoadjuvant, cisplatin-based chemotherapy followed by radical cystectomy (RC) is considered the gold standard therapy for muscle-invasive bladder based on randomized controlled trials. Across all tumor stages, this approach has been associated with the highest rates of disease-specific survival. However, RC is one of the most challenging procedures performed by urologic surgeons and carries with it significant risks of complications, hospital readmission, and even a small risk of mortality, in addition to lifestyle changes that can have long-term effects on well-being. For these reasons, bladder-sparing approaches are utilized in some highly selected patients. We reviewed the most recent evidence for bladder-sparing modalities for muscle-invasive urothelial bladder cancer and summarize those findings in this review article. Methods: We performed a PubMed literature review utilizing the key words “bladder preservation,” “trimodal therapy,” “muscle-invasive bladder cancer,” and “partial cystectomy” written in English, dating back to 1990. We excluded case reports. Results: Our search yielded more than 2000 articles which we screened. Some articles were then rejected due to inappropriate topic. In addition, we reviewed the most recent American Urological Association, National Comprehensive Cancer Network (NCCN), and European guidelines on muscle-invasive bladder cancer. We identified fifty relevant articles which are summarized in this text. In some rare instances, recommendations are based on expert opinion. Conclusions: Bladder preservation is often considered for quality of life considerations or in the setting of multiple medical comorbidities, and this remains oncologically appropriate even in 2016 in highly selected patients with muscle-invasive urothelial carcinoma of the bladder