Site effect assessment in Bishkek (Kyrgyzstan) using earthquake and noise recording data

Kyrgyzstan, which is located in the collision zone between the Eurasian and Indo-Australian lithosphere plates, is prone to large earthquakes as shown by its historical seismicity. Hence, an increase in the knowledge and awareness by local authorities and decision makers of the possible consequence of a large earthquake, based on improved seismic hazard assessments and realistic earthquake risk scenarios, is mandatory to mitigate the effects of an earthquake. To this regard, the Central Asia Cross-Border Natural Disaster Prevention (CASCADE) project aims to install a cross- border seismological and strong motion network in Central Asia and to support microzonation activities for the capitals of Kyrgyzstan, Uzbekistan, Kazakhstan, Tajikistan, and Turkmenistan. During the first phase of the project, a temporary seismological network of 19 stations was installed in the city of Bishkek, the capital of Kyrgyzstan. Moreover, single-station noise recordings were collected at nearly 200 sites. In this study, the site amplifications occurring in Bishkek are assessed by analyzing 56 earthquakes extracted from the data streams continuously acquired by the network, as well as from the single-station noise measurements. A broadband amplification (starting at ∼0:1 and 0.2 Hz), is shown by the standard spectral ratio (SSR) results of the stations located within the basin. The reliability of the observed low-frequency amplification was validated through a time–frequency analysis of denoised seismograms. Discrepancies between horizontal-to-vertical spectral ratio and SSR results are due to the large amplification of the vertical component of ground motion, probably due to the effect of converted waves. The single-station noise results, once their reliability was assessed by their comparison with the earthquake data, have been used to produce the first fundamental resonance frequency map for Bishkek, whose spatial variation shows a good agreement with the presence of an impedance contrast within the Tertiary sedimentary cover.Published3068-30824.1. Metodologie sismologiche per l'ingegneria sismicaJCR Journalope

Site effect assessment in Bishkek (Kyrgyzstan) using earthquake and noise recording data

Kyrgyzstan, which is located in the collision zone between the Eurasian and Indo-Australian lithosphere plates, is prone to large earthquakes as shown by its historical seismicity. Hence, an increase in the knowledge and awareness by local authorities and decision makers of the possible consequence of a large earthquake, based on improved seismic hazard assessments and realistic earthquake risk scenarios, is mandatory to mitigate the effects of an earthquake. To this regard, the Central Asia Cross-Border Natural Disaster Prevention (CASCADE) project aims to install a cross- border seismological and strong motion network in Central Asia and to support microzonation activities for the capitals of Kyrgyzstan, Uzbekistan, Kazakhstan, Tajikistan, and Turkmenistan. During the first phase of the project, a temporary seismological network of 19 stations was installed in the city of Bishkek, the capital of Kyrgyzstan. Moreover, single-station noise recordings were collected at nearly 200 sites. In this study, the site amplifications occurring in Bishkek are assessed by analyzing 56 earthquakes extracted from the data streams continuously acquired by the network, as well as from the single-station noise measurements. A broadband amplification (starting at ∼0:1 and 0.2 Hz), is shown by the standard spectral ratio (SSR) results of the stations located within the basin. The reliability of the observed low-frequency amplification was validated through a time–frequency analysis of denoised seismograms. Discrepancies between horizontal-to-vertical spectral ratio and SSR results are due to the large amplification of the vertical component of ground motion, probably due to the effect of converted waves. The single-station noise results, once their reliability was assessed by their comparison with the earthquake data, have been used to produce the first fundamental resonance frequency map for Bishkek, whose spatial variation shows a good agreement with the presence of an impedance contrast within the Tertiary sedimentary cover

Analysis of two human pre-ribosomal factors, bystin and hTsr1, highlights differences in evolution of ribosome biogenesis between yeast and mammals

Recent studies reveal that maturation of the 40S ribosomal subunit precursors in mammals includes an additional step during processing of the internal transcribed spacer 1 (ITS1), when compared with yeast Saccharomyces cerevisiae, even though the protein content of the pre-40S particle appears to be the same. Here, we examine by depletion with siRNA treatment the function of human orthologs of two essential yeast pre-ribosomal factors, hEnp1/bystin and hTsr1. Like their yeast orthologs, bystin is required for efficient cleavage of the ITS1 and further processing of this domain within the pre-40S particles, whereas hTsr1 is necessary for the final maturation steps. However, bystin depletion leads to accumulation of an unusual 18S rRNA precursor, revealing a new step in ITS1 processing that potentially involves an exonuclease. In addition, pre-40S particles lacking hTsr1 are partially retained in the nucleus, whereas depletion of Tsr1p in yeast results in strong cytoplasmic accumulation of pre-40S particles. These data indicate that ITS1 processing in human cells may be more complex than currently envisioned and that coordination between maturation and nuclear export of pre-40S particles has evolved differently in yeast and mammalian cells

1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation

BACKGROUND: Ribosome biogenesis is required for protein synthesis and cell proliferation. Ribosome subunits are assembled in the nucleolus following transcription of a 47S ribosome RNA precursor by RNA polymerase I and rRNA processing to produce mature 18S, 28S and 5.8S rRNAs. The 18S rRNA is incorporated into the ribosomal small subunit, whereas the 28S and 5.8S rRNAs are incorporated into the ribosomal large subunit. Pol I transcription and rRNA processing are coordinated processes and this coordination has been demonstrated to be mediated by a subset of U3 proteins known as t-UTPs. Up to date, five t-UTPs have been identified in humans but the mechanism(s) that function in the t-UTP(s) activation of Pol I remain unknown. In this study we have identified 1A6/DRIM, which was identified as UTP20 in our previous study, as a t-UTP. In the present study, we investigated the function and mechanism of 1A6/DRIM in Pol I transcription. METHODOLOGY/PRINCIPAL FINDINGS: Knockdown of 1A6/DRIM by siRNA resulted in a decreased 47S pre-rRNA level as determined by Northern blotting. Ectopic expression of 1A6/DRIM activated and knockdown of 1A6/DRIM inhibited the human rDNA promoter as evaluated with luciferase reporter. Chromatin immunoprecipitation (ChIP) experiments showed that 1A6/DRIM bound UBF and the rDNA promoter. Re-ChIP assay showed that 1A6/DRIM interacts with UBF at the rDNA promoter. Immunoprecipitation confirmed the interaction between 1A6/DRIM and the nucleolar acetyl-transferase hALP. It is of note that knockdown of 1A6/DRIM dramatically inhibited UBF acetylation. A finding of significance was that 1A6/DRIM depletion, as a kind of nucleolar stress, caused an increase in p53 level and inhibited cell proliferation by arresting cells at G1. CONCLUSIONS: We identify 1A6/DRIM as a novel t-UTP. Our results suggest that 1A6/DRIM activates Pol I transcription most likely by associating with both hALP and UBF and thereby affecting the acetylation of UBF

Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus

Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli

Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis

Final Pre-40S Maturation Depends on the Functional Integrity of the 60S Subunit Ribosomal Protein L3

Ribosomal protein L3 is an evolutionarily conserved protein that participates in the assembly of early pre-60S particles. We report that the rpl3[W255C] allele, which affects the affinity and function of translation elongation factors, impairs cytoplasmic maturation of 20S pre-rRNA. This was not seen for other mutations in or depletion of L3 or other 60S ribosomal proteins. Surprisingly, pre-40S particles containing 20S pre-rRNA form translation-competent 80S ribosomes, and translation inhibition partially suppresses 20S pre-rRNA accumulation. The GTP-dependent translation initiation factor Fun12 (yeast eIF5B) shows similar in vivo binding to ribosomal particles from wild-type and rpl3[W255C] cells. However, the GTPase activity of eIF5B failed to stimulate processing of 20S pre-rRNA when assayed with ribosomal particles purified from rpl3[W255C] cells. We conclude that L3 plays an important role in the function of eIF5B in stimulating 3′ end processing of 18S rRNA in the context of 80S ribosomes that have not yet engaged in translation. These findings indicate that the correct conformation of the GTPase activation region is assessed in a quality control step during maturation of cytoplasmic pre-ribosomal particles

Basin analysis using seismic interpretation as tools to examine the extent of a basin ore 'play'

Stratiform and stratabound base metal ores typically form in sedimentary basins during the overall rifting process with mineralising fluids transported along the growing normal faults. Understanding the detailed structural evolution, i.e. the timing, the growth and the extent of the faults, and the distribution and thickness of the syn-faulting sedimentary packages, is critical for focusing exploration efforts. In this paper, we describe how seismic interpretation and basin analysis techniques can help to do this. We assess the potential for Pb-Zn mineralisation within the Northumberland Trough, northern England, in the context of the wider Early Carboniferous basin evolution and the associated base metal ores. Through structural interpretation of seismic reflection data, we consider the detailed evolution of the fault geometries and sedimentation in time and space, to show the extent and distribution of the Early Carboniferous faulting and growth packages at depth in the study area. We conclude that basin evolution and structural framework in northern England is very similar to that associated with the significant Pb-Zn mineralisation in Ireland. We suggest a refined model for the Carboniferous evolution of this part of the basin. The study demonstrates how the techniques of basin analysis can be a used in ore exploration to establish whether the basic structural and sedimentary framework exists to enable mineralisation. In addition to assessing the general potential of base metal mineralisation, a more precise identification of potentially suitable areas for further investigation can be made. The seismic data and basin analysis approach used in this paper and exemplified through the Northumberland case should be directly applicable to any basin ore 'play' associated with rifting and/or sedimentation. The added, significant advantage of this method is the ability to assess the 3D fault geometries, including fault linkage and growth in space and time, and the associated sedimentation - an unachievable outcome if relying solely on other geophysical and geological data traditionally used in regional ore exploration

Integrated Multi-Parameter Exploration Footprints of the Canadian Malartic Disseminated Au, McArthur River-Millennium Unconformity U, and Highland Valley Porphyry Cu Deposits: Preliminary Results from the NSERC-CMIC Mineral Exploration Footprints Research Network

Mineral exploration in Canada is increasingly focused on concealed and deeply buried targets, requiring more effective tools to detect large-scale ore-forming systems and to vector from their most distal margins to their high grade cores. A new generation of ore system models is required to achieve this. The Mineral Exploration Footprints Research Network is a consortium of 70 faculty, research associates, and students from 20 Canadian universities working with 30 mining, mineral exploration, and mining service providers to develop new approaches to ore system modelling based on more effective integration and visualization of multi-parameter geological-structural-mineralogical-lithogeochemical-petrophysical-geophysical exploration data. The Network is developing the next generation ore system models and exploration strategies at three sites based on integrated data visualization using self-consistent 3D Common Earth Models and geostatistical/machine learning technologies. Thus far over 60 footprint components and vectors have been identified at the Canadian Malartic stockwork-disseminated Au deposit, 20–30 at the McArthur-Millennium unconformity U deposits, and over 20 in the Highland Valley porphyry Cu system. For the first time, these are being assembled into comprehensive models that will serve as landmark case studies for data integration and analysis in the today’s challenging exploration environment

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation