O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity

Nucleic acids are under constant assault from endogenous and environmental agents that alter their physical and chemical properties. O6-methylation of guanosine (m(6)G) is particularly notable for its high mutagenicity, pairing with T, during DNA replication. Yet, while m(6)G accumulates in both DNA and RNA, little is known about its effects on RNA. Here, we investigate the effects of m(6)G on the decoding process, using a reconstituted bacterial translation system. m(6)G at the first and third position of the codon decreases the accuracy of tRNA selection. The ribosome readily incorporates near-cognate aminoacyl-tRNAs (aa-tRNAs) by forming m(6)G-uridine codon-anticodon pairs. Surprisingly, the introduction of m(6)G to the second position of the codon does not promote miscoding, but instead slows the observed rates of peptide-bond formation by \u3e1000-fold for cognate aa-tRNAs without altering the rates for near-cognate aa-tRNAs. These in vitro observations were recapitulated in eukaryotic extracts and HEK293 cells. Interestingly, the analogous modification N6-methyladenosine (m(6)A) at the second position has only a minimal effect on tRNA selection, suggesting that the effects on tRNA selection seen with m(6)G are due to altered geometry of the base pair. Given that the m6G:U base pair is predicted to be nearly indistinguishable from a Watson-Crick base pair, our data suggest that the decoding center of the ribosome is extremely sensitive to changes at the second position. Our data, apart from highlighting the deleterious effects that these adducts pose to cellular fitness, shed new insight into decoding and the process by which the ribosome recognizes codon-anticodon pairs

Ribosomes Left in the Dust: Diverse Strategies for Peptide-Mediated Translation Stalling

In two recent papers, Arenz et al. (2014a) and Bischoff et al. (2014) provide structural insights into drug-induced, peptide-mediated stalling of the ribosome

An Active Role for the Ribosome in Determining the Fate of Oxidized mRNA

Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity of the selection process, suggesting that the modification stalls the translational machinery. Consistent with these findings, 8-oxoG mRNAs were observed to accumulate and associate with polyribosomes in yeast strains in which no-go decay is compromised. Our data provide compelling evidence that mRNA-surveillance mechanisms have evolved to cope with damaged mRNA

The elevated Curie temperature and half-metallicity in the ferromagnetic semiconductor Lax_{x}Eu1−x_{1-x}O

Here we study the effect of La doping in EuO thin films using SQUID magnetometry, muon spin rotation ($\mu$SR), polarized neutron reflectivity (PNR), and density functional theory (DFT). The $\mu$SR data shows that the La$_{0.15}$Eu$_{0.85}$O is homogeneously magnetically ordered up to its elevated $T_{\rm C}$. It is concluded that bound magnetic polaron behavior does not explain the increase in $T_{\rm C}$ and an RKKY-like interaction is consistent with the $\mu$SR data. The estimation of the magnetic moment by DFT simulations concurs with the results obtained by PNR, showing a reduction of the magnetic moment per La$_{x}$Eu$_{1-x}$O for increasing lanthanum doping. This reduction of the magnetic moment is explained by the reduction of the number of Eu-4$f$ electrons present in all the magnetic interactions in EuO films. Finally, we show that an upwards shift of the Fermi energy with La or Gd doping gives rise to half-metallicity for doping levels as high as 3.2 %.Comment: 7 pages, 11 figure

Enhanced situational awareness and decision support for operators of future distributed power network architectures

This paper describes scenarios proposed for a control room decision support system aimed at future power network operators. The purpose is to consider the requirements of the future control room from the perspective of the operator under the conditions of a significant frequency excursion incident. The control room visualisation and decision support functionality for aiding the operator in restoring the frequency to its target value will be considered. The analysis takes place within the Web-of-Cells framework, adopted to deal with power system control through a web of subsystems, called cells, which are highly automated, and operated by Cell Operators

Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer

BACKGROUND: Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. CASE PRESENTATION: We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. CONCLUSION: Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology

The Demand for Military Spending in Egypt

Egypt plays a pivotal role in the security of the Middle East as the doorway to Europe and its military expenditure reflects its involvement in the machinations of such an unstable region, showing considerable variation over the last 40 years. These characteristics make it a particularly interesting case study of the determinants of military spending. This paper specifies and estimates an econometric model of the Egyptian demand for military spending, taking into account important strategic and political factors. Both economic and strategic factors are found to play a role in determining military burden/spending, with clear positive effects of lagged military burden, suggesting some sort of institutional inertia, plus negative output and net exports effects. The strategic effect as a result of the impact of Israel's military burden is mostly positive and significant, though its impact is reduced when the impact of important strategic events are taken into account. The military spending of Egypt's allies Jordan and Syria generally seems to have had no effect on Egypt's spending. These results are consistent over a range of econometric techniques. © 2013 © 2013 Taylor & Francis

Assessing the Efficiency of Remote Sensing and Machine Learning Algorithms to Quantify Wheat Characteristics in the Nile Delta Region of Egypt

Monitoring strategic agricultural crops in terms of crop growth performance, by accurate cost-effective and quick tools is crucially important in site-specific management to avoid crop reductions. The availability of commercial high resolution satellite images with high resolution (spatial and spectral) as well as in situ spectra measurements can help decision takers to have deep insight on crop stress in a certain region. The research attempts to examine remote sensing dataset for forecasting wheat crop (Sakha 61) characteristics including the leaf area index (LAI), plant height (plant-h), above ground biomass (AGB) and Soil Plant Analysis Development (SPAD) value of wheat across non-stress, drought and salinity-induced stress in the Nile Delta region. In this context, the ability of in situ spectroradiometry measurements and QuickBird high resolution images was evaluated in our research. The efficiency of Random Forest (RF) and Artificial Neural Network (ANN), mathematical models was assessed to estimate the four measured wheat characteristics based on vegetation spectral reflectance indices (V-SRIs) extracted from both approaches and their interactions. Field surveys were carried out to collect in situ spectroradiometry measurements concomitant with the acquisition of QuickBird imagery. The results demonstrated that several V-SRIs extracted from in situ spectroradiometry data and the QuickBird image correlated with the LAI, plant-h, AGB, and SPAD value of wheat crop across the study site. The determination coefficient (R2) values of the association between V-SRIs of in situ spectroradiometry data and various determined wheat characteristics varied from 0.26 to 0.85. The ANN-GSIs-3 was found to be the optimum predictive model, demonstrating a greater relationship between the advanced features and LAI. The three features of V-SRIs comprised in this model were strongly significant for the prediction of LAI. The attained results indicated high R2 values of 0.94 and 0.86 for the training and validation phases. The ANN-GSIs-3 model constructed for the determination of chlorophyll in the plant which had higher performance expectations (R2 = 0.96 and 0.92 for training and validation datasets, respectively). In conclusion, the results of our study revealed that high resolution remote sensing images such as QuickBird or similar imagery, and in situ spectroradiometry measurements have the feasibility of providing necessary crop monitoring data across non-stressed and stressed (drought and salinity) conditions when integrating V-SRIs with ANN and RF algorithms

Complete Genome Sequence of Mycobacterium fortuitum subsp. fortuitum Type Strain DSM46621

Mycobacterium fortuitum is a member of the rapidly growing nontuberculous mycobacteria (NTM). It is ubiquitous in water and soil habitats, including hospital environments. M. fortuitum is increasingly recognized as an opportunistic nosocomial pathogen causing disseminated infection. Here we report the genome sequence of M. fortuitum subsp. fortuitum type strain DSM46621