Brunivey1791

The eukaryotic replisome, organized around the Cdc45-MCM-GINS (CMG) helicase, orchestrates chromosome replication. Multiple factors associate directly with CMG, including Ctf4 and the heterotrimeric fork protection complex (Csm3/Tof1 and Mrc1), which has important roles including aiding normal replication rates and stabilizing stalled forks. How these proteins interface with CMG to execute these functions is poorly understood. Here we present 3 to 3.5 Å resolution electron cryomicroscopy (cryo-EM) structures comprising CMG, Ctf4, and the fork protection complex at a replication fork. The structures provide high-resolution views of CMG-DNA interactions, revealing a mechanism for strand separation, and show Csm3/Tof1 "grip" duplex DNA ahead of CMG via a network of interactions important for efficient replication fork pausing. Although Mrc1 was not resolved in our structures, we determine its topology in the replisome by cross-linking mass spectrometry. Collectively, our work reveals how four highly conserved replisome components collaborate with CMG to facilitate replisome progression and maintain genome stability. During social transmission of food preference (STFP), the combination of an olfactory sensory input with a social cue induces long-term memory of a food odor. How a social cue produces long-term learning of an olfactory input, however, remains unknown. Here we show that the neurons of the anterior olfactory nucleus (AON), which form abundant synaptic projections onto granule cells in the olfactory bulb (OB), express the synaptogenic molecule C1ql3. Deletion of C1ql3 in the dorsolateral AON impaired synaptic AON→OB connections and abolished acquisition, but not recall, of STFP memory without significantly affecting basal olfaction. Moreover, deletion in granule cells of the OB of Bai3, a postsynaptic GPCR that binds C1ql3, similarly suppressed synaptic transmission at AON→OB projections and abolished acquisition, but not recall, of STFP memory. Thus, synaptic AON→OB connections are selectively required for STFP memory acquisition and are formed by an essential interaction of presynaptic C1ql3 with postsynaptic Bai3. A 52 years old woman, asymptomatic, with no significant medical history, presented to a thoracic surgery department for excision of a giant mediastinal mass that was incidentally detected during a routine abdominal ultrasound. Various imaging methods (echocardiography, chest X-ray, CT-scan, MRI) located the mediastinal mass as paracardiac and the excision using video-assisted thoracoscopic surgery (VATS) was proposed, in general thoracic surgery department. Although initially considered a paracardiac mass, intraoperatively the tumor location proved to be intrapericardial. Reaching the limits of VATS, a median sternotomy and longitudinal pericardiotomy were performed, demonstration a right atrium tumor with intrapericardial extension. At this stage, the excision was considered impossible without cardiopulmonary bypass and cardiac arrest. Having this information, the case was deferred to cardiovascular surgery, one week after and, a complete resection of the tumor was performed without incidents. Both atria were reconstructed with patches of autologous and bovine pericardium. The postoperative outcome of the patient was very good and the histopathology report showed that the tumor was a cavernous hemangioma. The literature was reviewed for this pathology. a rare case of a giant cavernous hemangioma of the heart, with diagnostic pitfalls had a successful multidisciplinary staged approach. Celsius.The pancreatic localization of the hydatid cyst is exceptional, even in countries where hydatid disease is considered endemic. We describe a female patient, 63 years old, with hydatid cyst of the pancreas. The diagnosis was difficult because the presentation was that of an epigastric cyst of unknown origin, with no suggestive radiological and ultrasonography features. We performed a laparoscopic exploration of abdominal cavity which revealed a retrogastric cystic mass developed from the pancreatic body. The surgical treatment consisted in puncture, evacuation of proligera, lavage with hypertonic serum, partial excision of the pericyst and drainage of the cavity. The postoperative course was uneventfull and the patient was released after 5 days. The follow-up at 6, 12 and 24 month did not show relapse. Through this observation and a review of the literature, we discuss the diagnostic and therapeutic difficulties of this rare localization of the hydatid cyst. Hydatid cyst is a rare cause of a cystic lesion of the pancreas, especially in endemic areas. Surgery still remains the most effective treatment option. Laparoscopic approach is feasible and secure but requires a trained team with experience in minimally invasive surgery. Celsius.Biliary atresia is the most frequent cause for neonatal obstructive cholestasis. Hepatoportoenterostomy (HPE) is the only method allowing survival until liver transplantation. For a maximum rate of success, the HPE procedure has to be performed within the 60 days of life. find more We aimed to create an experimental model for relieving obstructive cholestasis. In 20 Wistar rats selective bile duct obstruction was induced by the microsurgical ligature of the bile ducts corresponding to the median and left lateral liver lobes. After four weeks surgical re-intervention was carried out and HPE was performed microsurgically on the hilum of the median and left lateral liver lobes. One week after HPE, the integrity of the anastomosis and the hepatic changes were assessed. The survival rate throughout the study was 90%. The surgical re-intervention revealed hepatic-hilum adhesions, with fibrosis. Microscopically, an initial fibrogenic repair was identified, equivalent of moderate cholestasis. After the HPE, there was no bile leak from the anastomosis and no biliary peritonitis. The evolution was marked by a reduction in food intake. The experimental model we propose for the HPE is reliable by using microsurgical techniques. Based on it, one can study the changes induced by the bile duct obstruction. Celsius.