Insight into siderophore-carrying peptide biosynthesis: enterobactin is a precursor for microcin E492 posttranslational modification

Microcin E492-producing bacteria secrete both unmodified and posttranslationally modified microcins. The modification consists of a C-glucosylated linear trimer of N-(2,3-dihydroxybenzoyl)-l-serine, a catecholate siderophore related to salmochelins and enterobactin. We show here that repression of enterobactin biosynthesis inhibits the acquisition of microcin E492 posttranslational modification, as monitored by high-performance liquid chromatography and mass spectrometry. Furthermore, exogenous enterobactin restored the production of posttranslationally modified microcin in a bacterial strain deficient in enterobactin synthesis. We thus concluded that enterobactin serves as a precursor for the synthesis of the posttranslationally modified microcin and that the unmodified microcin is an incompletely processed form of mature microcin E492. Gene disruption experiments showed that MceC and MceD, two enzymes encoded by the mceABCDEFGHIJ gene cluster, are involved in the synthesis of the microcin E492 posttranslational modification, as followed by mass spectrometry. Genes homologous to iroB and iroD, required for the conversion (linearization and C-glycosylation) of enterobactin into salmochelins, efficiently complemented mceC and mceD, respectively. Based on our results, a model is proposed for the biosynthesis of the mature siderophore-carrying peptide.     

Landmark Series: A Review of Landmark Studies in the Treatment of Primary Localized Retroperitoneal Sarcoma

Annals of Surgical Oncology - Primary localized retroperitoneal soft tissue sarcomas (RPS) have shorter survival than other soft tissue sarcoma sites owing to higher local recurrence rates...     

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Annals of Surgical Oncology - Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly...     

Parietal network underlying movement control: disturbances during subcortical electrostimulation

Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.     

Results of a Surgeon-Directed Quality Improvement Project on Breast Cancer Surgery Outcomes in South-Central Ontario

Background

Gaps in breast cancer (BC) surgical care have been identified. We have completed a surgeon-directed, iterative project to improve the quality of BC surgery in South-Central Ontario.

Methods

Surgeons performing BC surgery in a single Ontario health region were invited to participate. Interventions included: audit and feedback (A&F) of surgeon-selected quality indicators (QIs), workshops, and tailoring interviews. Workshops and A&F occurred yearly from 2005–2012. QIs included: preoperative imaging; preoperative core biopsy; positive margin rates; specimen orientation labeling; intraoperative specimen radiography of nonpalpable lesions; T1/T2 mastectomy rates; reoperation for positive margins; sentinel lymph node biopsy (SLNB) rates, number of sentinel lymph nodes; and days to receive pathology report. Semistructured tailoring interviews were conducted to identify facilitators and barriers to improved quality. All results were disseminated to all surgeons performing breast surgery in the study region.

Results

Over 6 time periods, 1,828 BC charts were reviewed from 12 hospitals (8 community and 4 academic). Twenty-two to 40 participants attended each workshop. Sustained improvement in rates of positive margins, preoperative core biopsies, specimen orientation labeling, and SLNB were seen. Mastectomy rates and overall axillary staging rates did not change, whereas time to receive pathology report increased. The tailoring interviews concerning positive margins, SLNB, and reoperation for positive margins identified facilitators and barriers relevant to surgeons.

Conclusions

This surgeon-directed, regional project resulted in meaningful improvement in numerous QIs. There was consistent and sustained participation by surgeons, highlighting the importance of integrating the clinicians in a long-term, iterative quality improvement strategy in BC surgery.