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Modulation Factor (modulation + factor)
Selected AbstractsExpression of ribosome modulation factor (RMF) in Escherichia coli requires ppGppGENES TO CELLS, Issue 8 2001Kaori Izutsu Background During the transition from the logarithmic to the stationary phase, 70S ribosomes are dimerized into the 100S form, which has no translational activity. Ribosome Modulation Factor (RMF) is induced during the stationary phase and binds to the 50S ribosomal subunit, which directs the dimerization of 70S ribosomes. Unlike many other genes induced in the stationary phase, rmf transcription is independent of the sigma S. To identify the factors that regulate the growth phase-dependent induction of rmf, mutant strains deficient in global regulators were examined for lacZ expression directed by the rmf promoter. Results Among mutants of defective global regulators, only ppGpp deficiency (relA-spoT double mutant) drastically reduced the level of rmf transcription to less than 10% of that seen in the wild-type. Neither RMF nor 100S ribosomes were detected in this mutant in the stationary phase. rmf transcription correlated well with cellular ppGpp levels during amino acid starvation, IPTG induction of Ptrc-relA455 and in other mutants with artificially increased ppGpp levels. Although the growth rate also correlated inversely with both ppGpp levels and rmf transcription, the observation that the growth rates of the ppGpp-deficient and wild-type strains varied equivalently when grown on different media indicates that the link between rmf transcription and ppGpp levels is not a function of the growth rate. Conclusions ppGpp appears to positively regulate rmf transcription, at least in vivo. Thus, RMF provides a novel negative translational control by facilitating the formation of inactive ribosome dimers (100S) under the stringent circumstances of the stationary phase. [source] RMF inactivates ribosomes by covering the peptidyl transferase centre and entrance of peptide exit tunnelGENES TO CELLS, Issue 4 2004Hideji Yoshida In gram-negative bacteria such as Escherichia coli, protein synthesis is suppressed by the formation of 100S ribosomes under stress conditions. The 100S ribosome, a dimer of 70S ribosomes, is formed by ribosome modulation factor (RMF) binding to the 70S ribosomes. During the stationary phase, most of the 70S ribosomes turn to 100S ribosomes, which have lost translational activity. This 100S formation is called the hibernation process in the ribosome cycle of the stationary phase. If stationary phase cells are transferred to fresh medium, the 100S ribosomes immediately go back to active 70S ribosomes, showing that inactive 100S , active 70S interconversion is a major system regulating translation activity in stationary phase cells. To elucidate the mechanisms of translational inactivation, the binding sites of RMF on 23S rRNA in 100S ribosome of E. coli were examined by a chemical probing method using dimethyl sulphate (DMS). As the results, the nine bases in 23S rRNA were protected from DMS modifications and the modification of one base was enhanced. Interestingly A2451 is included among the protected bases, which is thought to be directly involved in peptidyl transferase activity. We conclude that RMF inactivates ribosomes by covering the peptidyl transferase (PTase) centre and the entrance of peptide exit tunnel. It is surprising that the cell itself produces a protein that seems to inhibit protein synthesis in a similar manner to antibiotics and that it can reversibly bind to and release from the ribosome in response to environmental conditions. [source] Expression of ribosome modulation factor (RMF) in Escherichia coli requires ppGppGENES TO CELLS, Issue 8 2001Kaori Izutsu Background During the transition from the logarithmic to the stationary phase, 70S ribosomes are dimerized into the 100S form, which has no translational activity. Ribosome Modulation Factor (RMF) is induced during the stationary phase and binds to the 50S ribosomal subunit, which directs the dimerization of 70S ribosomes. Unlike many other genes induced in the stationary phase, rmf transcription is independent of the sigma S. To identify the factors that regulate the growth phase-dependent induction of rmf, mutant strains deficient in global regulators were examined for lacZ expression directed by the rmf promoter. Results Among mutants of defective global regulators, only ppGpp deficiency (relA-spoT double mutant) drastically reduced the level of rmf transcription to less than 10% of that seen in the wild-type. Neither RMF nor 100S ribosomes were detected in this mutant in the stationary phase. rmf transcription correlated well with cellular ppGpp levels during amino acid starvation, IPTG induction of Ptrc-relA455 and in other mutants with artificially increased ppGpp levels. Although the growth rate also correlated inversely with both ppGpp levels and rmf transcription, the observation that the growth rates of the ppGpp-deficient and wild-type strains varied equivalently when grown on different media indicates that the link between rmf transcription and ppGpp levels is not a function of the growth rate. Conclusions ppGpp appears to positively regulate rmf transcription, at least in vivo. Thus, RMF provides a novel negative translational control by facilitating the formation of inactive ribosome dimers (100S) under the stringent circumstances of the stationary phase. [source] Two proteins, YfiA and YhbH, associated with resting ribosomes in stationary phase Escherichia coliGENES TO CELLS, Issue 12 2000Yasushi Maki Ribosomes in Escherichia coli change their composition and conformation in the stationary phase. Ribosome modulation factor (RMF) and ribosomal protein S22 are known to be associated with stationary phase ribosomes. RMF association causes the loss of translational activity and the dimerization of 70S ribosomes into 100S ribosomes, which may increase cell survival in the stationary phase. Two weakly acidic proteins having related amino acid sequences were found to be associated with E. coli ribosomes in the stationary phase. These proteins are the products of ORFs named yfiA and yhbH. The sum of the copy numbers of their product proteins, YfiA and YhbH, in the ribosomal particles was low in the log phase, but increased to nearly one in the stationary phase. YfiA was found in the 70S ribosomal fraction rather than the 100S. On the other hand, YhbH was detected exclusively in the 100S ribosomal fraction. When the stationary phase cells were transferred to fresh medium, YfiA and YhbH were found in the 70S ribosomal fraction, but not in the polysome fraction. Two proteins, YfiA and YhbH, associated with E. coli ribosomes were found to accumulate in the stationary phase, leading to the formation of several types of ribosomes. They are not likely to have roles in the elongation step of the translation in log phase cells, but are likely to be involved in the stabilization and preservation of ribosomes in the stationary phase, which might be necessary for cell survival. [source] ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapyJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2010JC Marsh Abstract Introduction:, The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials:, We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V100 , 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V100. Results:, In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V100 for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27,17.5). Conclusions:, It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose. [source] Burden of disease related to Parkinson's disease in Spain in the year 2000MOVEMENT DISORDERS, Issue 11 2005Esther Cubo MD Abstract We measured the burden caused by Parkinson's disease (PD) in Spain during the year 2000 and compared it against PD burden worldwide and in the European A subregion. Burden of disease (BoD) is an important factor in health policy. Disability-adjusted life years (DALY) as a measure of BoD is the result of adding years of life lost (YLL) and years lived with disability (YLD). The burden of PD (BPD) has not been studied in Spain. YLL were obtained from the Spanish death certificates and YLD from the estimated number of incident PD cases and the average PD duration. PD disability was calculated, using the Disability Weights for Diseases in the Netherlands. Prior PD DALY data for Europe and the world were obtained from the 2001 World Health Organization World Health Report. A discount rate of 3% and age-weighting modulation factor with K = 1 were used. In Spain, PD generated 67,582 DALY, comprising 6,351 (9.4%) YLL and 61,231 (90.6%) YLD. Most PD DALY (57.5%) occurred in the population 60 to 74 years of age. When PD DALY estimates were adjusted using the world population in 2000, Spain registered a PD DALY rate of 84 per 100,000 population, higher than both the world and European A subregion rates (24 and 35 per 100,000 population, respectively). PD burden in Spain in 2000 was high, with disability being the major contributing factor. Although BPD in Spain was greater than both world and European A subregion BPD, these differences should nevertheless be interpreted with caution. © 2005 Movement Disorder Society [source] | ||||||||||