Ribosome-Dependent ATPase Interacts with Conserved Membrane Protein in Escherichia coli to Modulate Protein Synthesis and Oxidative Phosphorylation

Elongation factor RbbA is required for ATP-dependent deacyl-tRNA release presumably after each peptide bond formation; however, there is no information about the cellular role. Proteomic analysis in Escherichia coli revealed that RbbA reciprocally co-purified with a conserved inner membrane protein of unknown function, YhjD. Both proteins are also physically associated with the 30S ribosome and with members of the lipopolysaccharide transport machinery. Genome-wide genetic screens of rbbA and yhjD deletion mutants revealed aggravating genetic interactions with mutants deficient in the electron transport chain. Cells lacking both rbbA and yhjD exhibited reduced cell division, respiration and global protein synthesis as well as increased sensitivity to antibiotics targeting the ETC and the accuracy of protein synthesis. Our results suggest that RbbA appears to function together with YhjD as part of a regulatory network that impacts bacterial oxidative phosphorylation and translation efficiency

Tension stimulation drives tissue formation in scaffold-free systems

Scaffold-free systems have emerged as viable approaches for engineering load-bearing tissues. However, the tensile properties of engineered tissues have remained far below the values for native tissue. Here, by using self-assembled articular cartilage as a model to examine the effects of intermittent and continuous tension stimulation on tissue formation, we show that the application of tension alone, or in combination with matrix remodelling and synthesis agents, leads to neocartilage with tensile properties approaching those of native tissue. Implantation of tension-stimulated tissues results in neotissues that are morphologically reminiscent of native cartilage. We also show that tension stimulation can be translated to a human cell source to generate anisotropic human neocartilage with enhanced tensile properties. Tension stimulation, which results in nearly sixfold improvements in tensile properties over unstimulated controls, may allow the engineering of mechanically robust biological replacements of native tissue

CyberKnife radiosurgery of skull-base tumors: A UK center experience

The study aim was to evaluate patient individualized Cyberknife® treatment for heterogeneous skull-base tumors. Patients treated between 2009 and 2013 at The Harley Street Clinic were studied. In total, 66 patients received 15–30 Gy in 1–5 fractions to a median planning target volume (PTV) of 6.4 cc, including patients with secondary, multiple, residual and recurrent tumors, and those with tumors of uncertain pathological type. Outcome analysis was pragmatically restricted to 35 patients who had single, primary tumors treated with curative intent, and sufficient diagnostic and outcome information. Sixteen vestibular schwannoma patients with median PTV 3.8 cc (range 0.81–19.6) received 18–25 Gy in 3–5 fractions: 81% showed no acute toxicity, 50% reported no late toxicity, 71% of symptoms were stable/improved and local control was 100% at 11.4 months median follow-up. Twelve meningioma patients with median PTV of 5.5 cc (range 0.68–22.3) received 17–30 Gy in 1–5 fractions: 83% experienced no acute toxicity, 33% reported no late toxicity, 88% of symptoms were stable/improved and local control was 100% at 22.1 months median follow-up. Seven patients with other tumor types with median PTV of 24.3 cc (range 7.6–100.5) received 15–28.5 Gy in 1–5 fractions: 57% experienced no acute toxicity, 57% reported no late toxicities, 66% of symptoms were stable and local control was 43% at 14.9 months median follow-up. When tumor types were considered together, smaller tumors (PTV < 6.4 cc) showed reduced acute toxicity (p = 0.01). Overall, smaller benign tumors showed low acute toxicity, excellent local control, and good symptom management: a focus on enhanced neurological preservation may refine outcomes. For other tumor types outcome was encouraging: a focus on optimal dose and fractionation scheduling may reduce toxicity and improve local control. Individual patient experiences are detailed where valuable lessons were gained for optimizing local control and minimizing toxicity

Refining the Intraoperative Identification of Suspected High-Grade Glioma Using a Surgical Fluorescence Biomarker: GALA BIDD Study Report

BackgroundImproving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling.MethodsWe designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery.ResultsA total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled. Among the 99 patients who received 5-ALA, 89 patients were eligible to assess the correlation of fluorescence with diagnosis as per protocol. Of these 89, 81 patients had visible fluorescence at surgery, and 8 patients had no fluorescence. A total of 80 out of 81 fluorescent patients were diagnosed as high-grade gliomas on postoperative central review with 1 low-grade glioma case. Among the eight patients given 5-ALA who did not show any visible fluorescence, none were high-grade gliomas, and all were low-grade gliomas. Of the seven patients suspected radiologically of malignant transformation of low-grade gliomas and with visible fluorescence at surgery, six were diagnosed with high-grade gliomas, and one had no tissue collected.ConclusionIn patients where there is clinical suspicion, visible 5-ALA fluorescence has clinical utility as an intraoperative surgical biomarker of high-grade gliomas and can aid surgical decision-making and sampling. Further studies assessing the use of 5-ALA to assess malignant transformation in all diffuse gliomas may be valuable