Regulation of Glia Number in Drosophila by Rap/Fzr, an Activator of the Anaphase-Promoting Complex, and Loco, an RGS Protein

Glia mediate a vast array of cellular processes and are critical for nervous system development and function. Despite their immense importance in neurobiology, glia remain understudied and the molecular mechanisms that direct their differentiation are poorly understood. Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase complex well characterized for its role in cell cycle progression. In this study, we have uncovered a novel cellular role for Rap/Fzr. Loss of rap/fzr function leads to a marked increase in the number of glia in the nervous system of third instar larvae. Conversely, ectopic expression of UAS-rap/fzr, driven by repo-GAL4, results in the drastic reduction of glia. Data from clonal analyses using the MARCM technique show that Rap/Fzr regulates the differentiation of surface glia in the developing larval nervous system. Our genetic and biochemical data further indicate that Rap/Fzr regulates glial differentiation through its interaction with Loco, a regulator of G-protein signaling (RGS) protein and a known effector of glia specification. We propose that Rap/Fzr targets Loco for ubiquitination, thereby regulating glial differentiation in the developing nervous system

Minimally Invasive Aortobiilliofemoral Endarterectomy for Aortoiliac Occlusive Disease Is a Compelling Alternative to Bypass

INTRODUCTION:: Aortobifemoral bypass is a time-honored, durable surgery allowing restoration of lower extremity blood. However, the potential for significant complications exists, impacting mortality, morbidity, and quality of life. Minimally invasive aortobiiliofemoral endarterectomy offers an alternative to prosthetic bypass and its associated complications. Here, we present a case series using remote endarterectomy for aortoiliac occlusive disease. METHODS:: Nine patients with aortoiliac occlusive disease were treated at a single institution, by a single surgeon, with direct and remote endarterectomy combination. Standard femoral access approach was used. A limited longitudinal distal aorta arteriotomy into the right common iliac artery to the hypogastric bifurcation was made. Then, an open thromboendarterectomy was performed. Circumferential common femoral endarterectomies were performed bilaterally and the plaque transected, allowing manually controlled Vollmar ring passage proximally to the iliac bifurcation on the right and the aortic bifurcation on the left. Aortoiliac arteriotomy was closed, followed by the femoral arteriotomies. Morbidity, secondary interventions, recurrent stenosis (adjacent segment velocity ratios \u3e=2), ankle-brachial index (ABI), and patency rates were tracked postoperatively for 6 years. Kaplan-Meier life-table analysis was used to determine patency rates per the criteria of SVS and ISCS. RESULTS:: The average age was 59.1 years (54-87 years), and 88% were male. Comorbidities included hypertension (75%), former/current smokers (100%), and prior PAD surgical intervention (38%). Revascularization of 100% was achieved, with average ABI improving from 0.42 preoperatively to 0.92 postoperatively (0.91 at 8-month follow-up). Six-year patency rate was 100% without reintervention. Incidence of myocardial infarction, stroke, death, amputation, intestinal ischemia, sexual dysfunction, and aneurysmal degeneration was zero after 6 years of follow-up. CONCLUSION:: Minimally invasive aortobiiliofemoral endarterectomy is a viable alternative to aortobifemoral bypass for the treatment of aortoiliac occlusive disease, allowing reestablishment of normal anatomic anatomy while avoiding the use of prosthetic material. Patency rates in this series was 100% at 6 years, with minimal postoperative complications or morbidity