Optimization of Ribosome Structure and Function by rRNA Base Modification

BACKGROUND: Translating mRNA sequences into functional proteins is a fundamental process necessary for the viability of organisms throughout all kingdoms of life. The ribosome carries out this process with a delicate balance between speed and accuracy. This work investigates how ribosome structure and function are affected by rRNA base modification. The prevailing view is that rRNA base modifications serve to fine tune ribosome structure and function. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, yeast strains deficient in rRNA modifications in the ribosomal peptidyltransferase center were monitored for changes in and translational fidelity. These studies revealed allele-specific sensitivity to translational inhibitors, changes in reading frame maintenance, nonsense suppression and aa-tRNA selection. Ribosomes isolated from two mutants with the most pronounced phenotypic changes had increased affinities for aa-tRNA, and surprisingly, increased rates of peptidyltransfer as monitored by the puromycin assay. rRNA chemical analyses of one of these mutants identified structural changes in five specific bases associated with the ribosomal A-site. CONCLUSIONS/SIGNIFICANCE: Together, the data suggest that modification of these bases fine tune the structure of the A-site region of the large subunit so as to assure correct positioning of critical rRNA bases involved in aa-tRNA accommodation into the PTC, of the eEF-1A•aa-tRNA•GTP ternary complex with the GTPase associated center, and of the aa-tRNA in the A-site. These findings represent a direct demonstration in support of the prevailing hypothesis that rRNA modifications serve to optimize rRNA structure for production of accurate and efficient ribosomes

RRx-001, A novel dinitroazetidine radiosensitizer

The ‘holy grail’ in radiation oncology is to improve the outcome of radiation therapy (RT) with a radiosensitizer—a systemic chemical/biochemical agent that additively or synergistically sensitizes tumor cells to radiation in the absence of significant toxicity. Similar to the oxygen effect, in which DNA bases modified by reactive oxygen species prevent repair of the cellular radiation damage, these compounds in general magnify free radical formation, leading to the permanent “fixation” of the resultant chemical change in the DNA structure. The purpose of this review is to present the origin story of the radiosensitizer, RRx-001, which emerged from the aerospace industry. The activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews

How do women entrepreneurs use the virtual network Facebook? The impact of gender

peer reviewedThis paper examines the views and attitudes of a sample of 228 female entrepreneurs towards the virtual social network Facebook. It identifies the main trends and uses statistical analysis to evaluate the impact of their gendered sector of activity and of their self-perception on their view of this network as a response to gender-related difficulties and their use of it in relation to their activities and objectives. The study further investigates how Facebook may encourage and support women’s networks as well as benefit women-owned businesses. It highlights certain implications for public and private initiatives and underlines the potential of this and other virtual social networking sites for women’s entrepreneurship.Diane

Chemotactic activity of culture supernatants of free and encapsulated pancreatic rat islets towards peritoneal macrophages

Longterm efficiency of encapsulated pancreatic islet transplantation is limited by macrophagic reaction at the surface of biocompatible membrane. The aim of this work was to investigate the influence of soluble factors released by free and encapsulated islets on macrophage chemotaxis. The culture mediums conditioned for 6 days by free and encapsulated rat islets were incubated with peritoneal murine, rat allo and syngenic macrophages to study their migration. Culture supernatants of rat fibroblasts and acinar cells, glucose-stimulated free rat islets and supernatants of free rat islets treated by heat and proteinase K were also tested for their chemotactic activity. Islets encapsulation decreased the chemotactic activity of culture medium conditioned for 6 days by free rat islets on murine (1.66 +/- 0.20 vs. 3.10 +/- 0.23; p < 0.001, n = 5) and rat allogenic macrophages (1.63 +/- 0.21 vs. 4.70 +/- 0.36; p < 0.001, n = 9). There was no migration of rat macrophages towards syngenic islets. Fibroblasts exhibited a very strong chemotactic effect as compared to acinar cells. Insulin was not involved in macrophage migration. Proteinase K treatment of culture supernatant of free rat islets totally inhibited the chemotactic activity. After heating at 56 degrees C and 100 degrees C, this activity was reduced to 41 +/- 7% and 32 +/- 5% of the initial activity, respectively. In conclusion, pancreatic islet stimulated macrophage migration by release of immunological specific proteins partly retained by macroencapsulation

Surface treatment of polycarbonate films aimed at biomedical application

Aiming to encapsulate pancreatic islets, a biocompatible polycarbonate membrane (What-man) was treated with plasma argon in order to improve its surface properties. The argon plasma treatment decreased the hydrophobicity of the membrane by fixing polyvinylpyrrolidone (PVP) at the surface. The water angle contact decreased from 47degrees to 20degrees after this treatment, while the structure and pore diameter were preserved. The treatment also increased significantly the water permeability from 62 +/- 8 ml/min to 200 +/- 29 ml/min (P < 0.001). ToF-SIMS analyses revealed that the argon plasma treatment of the membrane allowed the installation of an uniform PVP layer at the surface. The concentration equilibrum in glucose was reached after 8 h diffusion for the treated membrane, while it was only 32.4 +/- 8.6% (P < 0.01) for the untreated membrane. The biocompatibility of the polycarbonate membrane was assessed after one month of implantation in rats and proved to be unaffected by the surface treatment. In conclusion, the present study provided sufficient information to establish a relationship between the physicochemical modifications of the PVP-plasma-treated polycarbonate membrane and the improvement in its permeability

Surface treatment of polycarbonate films aimed at biomedical application

Aiming to encapsulate pancreatic islets, a biocompatible polycarbonate membrane (Whatman) was treated with plasma argon in order to improve its surface properties. The argon plasma treatment decreased the hydrophobicity of the membrane by fixing polyvinylpyrrolidone (PVP) at the surface. The water angle contact decreased from 47 degrees to 20 degrees after this treatment, while the structure and pore diameter were preserved. The treatment also increased significantly the water permeability from 62 +/- 8 ml/min to 200 +/- 29 ml/min (P < 0.001). ToF-SIMS analyses revealed that the argon plasma treatment of the membrane allowed the installation of an uniform PVP layer at the surface. The concentration equilibrum in glucose was reached after 8 h diffusion for the treated membrane, while it was only 32.4 +/- 8.6% (P < 0.01) for the untreated membrane. The biocompatibility of the polycarbonate membrane was assessed after one month of implantation in rats and proved to be unaffected by the surface treatment. In conclusion, the present study provided sufficient information to establish a relationship between the physicochemical modifications of the PVP-plasma-treated polycarbonate membrane and the improvement in its permeability