Structural and mechanistic basis of RNA processing by protein-only ribonuclease P enzymes

Ribonuclease P (RNase P) enzymes are responsible for the 5′ processing of tRNA precursors. In addition to the well-characterised ribozyme-based RNase P enzymes, an evolutionarily distinct group of protein-only RNase Ps exists. These proteinaceous RNase Ps (PRORPs) can be found in all three domains of life and can be divided into two structurally different types: eukaryotic and pro- karyotic. Recent structural studies on members of both families reveal a surpris- ing diversity of molecular architectures, but also highlight conceptual and mechanistic similarities. Here, we provide a comparison between the different types of PRORP enzymes and review how the combination of structural, bio- chemical, and biophysical studies has led to a molecular picture of protein- mediated tRNA processing

Agro-Morphological Variability Assessment of Common Bean (Phaseolus vulgaris L.) Genotypes in High Hill Jumla, Nepal

Common bean (Phaseolus vulgaris L.) is the most important leguminous crop widely grown from Terai to high hills of Nepal covering 10,529 hectare land producing 15550 mt with the productivity of 1477 kgha-1 and Jumla occupies almost 21% of the total bean cultivated area of the country. For the experiment, twelve genotypes of common bean were collected from different locations of Nepal. The experiment was conducted at Agricultural Research Station Vijayanagar, Jumla Nepal from July, 2016 to October, 2016 in Randomized Complete Block Design with three replications and twelve treatments. Different agro-morphological characters were observed and wide variability was recorded in growth habit, flower color, seed color, seed shape, seed length (0.76-1.7cm), pod color, pod length(9.1-14.3 cm), plant height (57.1-116.5 cm), days to flowering (38-52 days) and maturity (74-90 days), number of pods plant-1 (9-22 seeds), number of seeds pod-1 (4-8 pods), hundred grain weight (18.3-54.7gm) and yield (2339-4164KgHa-1). Significant differences were found among genotypes for days to flowering, pod length, no of seeds pod-1 and yield hectare-1.The coefficients of determination illustrate the positive and significant association of grain yield hectare-1 with number of seeds pods-1, therefore these traits should be considered for genetic improvement through breeding

Assessment of home hazards for non-fatal childhood injuries in rural Nepal: A community survey

Background: Unintentional injuries in and around the home are important causes of preventable death and disability among young children globally. In Nepal, there is a lack of data regarding home injuries and home hazards to guide the development of effective interventions for preventing childhood home injuries. This study aimed to determine the burden of unintentional home injuries in children < 5 years in rural Nepal and quantify the injury hazards in their homes.Methods: A survey was conducted in 740 households in rural areas of the Makwanpur district during February and March 2015. The primary carer reported home injuries which occurred in the previous 3 months and data collector observation identified the injury hazards. Injury incidence, mechanism and the proportion of households with different hazards were described. Multivariable logistic regression explored associations between the number and type of home hazards and injuries.Results: Injuries severe enough to need treatment, or resulting in non-participation in usual activities for at least a day, were reported in 242/1042 (23.2%) children < 5 years. The mean number of injury hazards per household was 14.98 (SD=4.48), range of 3–31. Regression analysis found an estimated increase of 31% in the odds of injury occurrence associated with each additional injury hazard found in the home (adjusted OR 1.31; 95% CI 1.20 to 1.42).Conclusions: A high proportion of young children in rural Nepal sustained injuries severe enough to miss a day of usual activities. Increased frequency of hazards was associated with an increased injury risk

Structural basis of RNA processing by human mitochondrial RNase P

Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry out RNA cleavage and methylation by unknown mechanisms. Here, we present the cryo-EM structure of human mtRNase P bound to precursor tRNA, which reveals a unique mechanism of substrate recognition and processing. Subunits TRMT10C and SDR5C1 form a subcomplex that binds conserved mitochondrial tRNA elements, including the anticodon loop, and positions the tRNA for methylation. The endonuclease PRORP is recruited and activated through interactions with its PPR and nuclease domains to ensure precise pre-tRNA cleavage. The structure provides the molecular basis for the first step of RNA processing in human mitochondria

Obstetric consequences of subfertility : a retrospective cohort study

Funding No funding was received for this study. Acknowledgements We would like to acknowledge the help and expertise provided by Fiona Chaloner who performed the data linkage and extraction from the databases. We also thank the medical statistics team, University of Aberdeen, and in particular Dr Lorna Aucott, for their advice on the analysis of the data. We would also like to thank Margery Heath for proofreading and formatting the paper.Peer reviewedPostprintPostprin

Mitochondrien: wie die Gene im Kraftwerk der Zelle aktiviert werden

Mitochondria contain an organellar genome that encodes for subunits of the respiratory chain. Its coordinated expression is essential for eukaryotic life and defects in this process lead to severe disease. How- ever, the molecular mechanisms underlying mitochondrial gene expression remain poorly understood. Recent structural and functional studies have provided the first mechanistic insights into mitochondrial gene expression and highlight the evolutionarily unique nature of this system

Non-surgical interventions for pelvic organ prolapse in rural Nepal: a prospective monitoring and evaluation study

OBJECTIVES: Pelvic organ prolapse (POP) is a major cause of morbidity in Nepal, particularly affecting women in the rural communities. Women with POP in Nepal may suffer from symptoms for decades. At present, the Government of Nepal advocates surgical intervention but access to surgical care is inadequate. This report evaluated the feasibility of a non-surgical public health programme in rural Nepal, and describes risk factors associated with POP in this setting. DESIGN: Prospective monitoring and evaluation study of a new public health programme. SETTING: Baglung district, rural Nepal. PARTICIPANTS: Women with gynaecological symptoms of POP. MAIN OUTCOME MEASURES: Risk factors for disease progression were assessed using Fisher’s exact test, Pearson’s χ(2)-test and logistic regression analysis. RESULTS: Of the 74 women included in this analysis, 70.8% were diagnosed with stage 2 POP or greater. The majority of women did not have any further children following the onset of POP symptoms (63.5%). Duration of symptoms ranged from 2 months to 60 years, with 73.4% of women suffering for over 5 years and 28.4% suffering for over 20 years. Univariate analyses identified age at screening, age at onset of symptoms, the duration of symptoms and an associated rectocele as factors associated with increasing POP severity (p < 0.05). Kegel exercises were taught to 25 (33.8%) women with POP and ring pessaries were offered to 47 (63.5%) women with POP. CONCLUSIONS: Non-surgical interventions may provide an opportunity to address the significant burden of POP in rural Nepal

Oxidation mechanism in metal nanoclusters: Zn nanoclusters to ZnO hollow nanoclusters

Zn nanoclusters (NCs) are deposited by Low-energy cluster beam deposition technique. The mechanism of oxidation is studied by analysing their compositional and morphological evolution over a long span of time (three years) due to exposure to ambient atmosphere. It is concluded that the mechanism proceeds in two steps. In the first step, the shell of ZnO forms over Zn NCs rapidly up to certain limiting thickness: with in few days -- depending upon the size -- Zn NCs are converted to Zn-ZnO (core-shell), Zn-void-ZnO, or hollow ZnO type NCs. Bigger than ~15 nm become Zn-ZnO (core-shell) type: among them, NCs above ~25 nm could able to retain their initial geometrical shapes (namely triangular, hexagonal, rectangular and rhombohedral), but ~25 to 15 nm size NCs become irregular or distorted geometrical shapes. NCs between ~15 to 5 nm become Zn-void-ZnO type, and smaller than ~5 nm become ZnO hollow sphere type i.e. ZnO hollow NCs. In the second step, all Zn-void-ZnO and Zn-ZnO (core-shell) structures are converted to hollow ZnO NCs in a slow and gradual process, and the mechanism of conversion proceeds through expansion in size by incorporating ZnO monomers inside the shell. The observed oxidation behaviour of NCs is compared with theory of Cabrera - Mott on low-temperature oxidation of metal.Comment: 9 pages, 8 figure

Signatures of the disk-jet coupling in the Broad-line Radio Quasar 4C+74.26

Here we explore the disk-jet connection in the broad-line radio quasar 4C+74.26, utilizing the results of the multiwavelength monitoring of the source. The target is unique in that its radiative output at radio wavelengths is dominated by a moderately-beamed nuclear jet, at optical frequencies by the accretion disk, and in the hard X-ray range by the disk corona. Our analysis reveals a correlation (local and global significance of 96\% and 98\%, respectively) between the optical and radio bands, with the disk lagging behind the jet by $250 \pm 42$ days. We discuss the possible explanation for this, speculating that the observed disk and the jet flux changes are generated by magnetic fluctuations originating within the innermost parts of a truncated disk, and that the lag is related to a delayed radiative response of the disk when compared with the propagation timescale of magnetic perturbations along relativistic outflow. This scenario is supported by the re-analysis of the NuSTAR data, modelled in terms of a relativistic reflection from the disk illuminated by the coronal emission, which returns the inner disk radius $R_{\rm in}/R_{\rm ISCO} =35^{+40}_{-16}$. We discuss the global energetics in the system, arguing that while the accretion proceeds at the Eddington rate, with the accretion-related bolometric luminosity $L_{\rm bol} \sim 9 \times 10^{46}$ erg s$^{-1}$ $\sim 0.2 L_{\rm Edd}$, the jet total kinetic energy $L_\textrm{j} \sim 4 \times 10^{44}$ erg s$^{-1}$, inferred from the dynamical modelling of the giant radio lobes in the source, constitutes only a small fraction of the available accretion power.Comment: 9 pages and 6 figures, ApJ accepte