Seismotectonics and rupture process of the MW 7.1 2011 Van reverse-faulting earthquake, eastern Turkey, and implications for hazard in regions of distributed shortening

The 2011 October 23 MW 7.1 Van earthquake in eastern Turkey caused ~600 deaths and caused widespread damage and economic loss. The seismogenic rupture was restricted to 10-25 km in depth, but aseismic surface creep, coincident with outcrop fault exposures, was observed in the hours to months after the earthquake. We combine observations from radar interferometry, seismology, geomorphology and Quaternary dating to investigate the geological slip rate and seismotectonic context of the Van earthquake, and assess the implications for continuing seismic hazard in the region. Transient post-seismic slip on the upper Van fault started immediately following the earthquake, and decayed over a period of weeks; it may not fully account for our long-term surface slip-rate estimate of ≥ 0.5 mm yr-1. Post-seismic slip on the Bostaniçi splay fault initiated several days to weeks after the main shock, and we infer that it may have followed the MW 5.9 aftershock on the 9th November. The Van earthquake shows that updip segmentation can be important in arresting seismic ruptures on dip-slip faults. Two large, shallow aftershocks show that the upper 10 km of crust can sustain significant earthquakes, and significant slip is observed to have reached the surface in the late Quaternary, so there may be a continuing seismic hazard from the upper Van fault and the associated splay. The wavelength of folding in the hanging wall of the Van fault is dominated by the structure in the upper 10 km of the crust, masking the effect of deeper seismogenic structures. Thus, models of subsurface faulting based solely on surface folding and faulting in regions of reverse faulting may underestimate the full depth extent of seismogenic structures in the region. In measuring the cumulative post-seismic offsets to anthropogenic structures, we show that Structure-from-Motion can be rapidly deployed to create snapshots of postseismic displacement.We also demonstrate the utility of declassified Corona mission imagery (1960s-1970s) for geomorphic mapping in areas where recent urbanization has concealed the geomorphic markers

Statistical analysis of human boy movement and group interactions in response to music

Quantification of time series that relate to physiological data is challenging for empirical music research. Up to now, most studies have focused on time-dependent responses of individual subjects in controlled environments. However, little is known about time-dependent responses of between-subject interactions in an ecological context. This paper provides new findings on the statistical analysis of group synchronicity in response to musical stimuli. Different statistical techniques were applied to time-dependent data obtained from an experiment on embodied listening in individual and group settings. Analysis of inter group synchronicity are described. Dynamic Time Warping (DTW) and Cross Correlation Function (CCF) were found to be valid methods to estimate group coherence of the resulting movements. It was found that synchronicity of movements between individuals (human human interactions) increases significantly in the social context. Moreover, Analysis of Variance (ANOVA) revealed that the type of music is the predominant factor in both the individual and the social context

Organic matter control on the distribution of arsenic in lake sediments impacted by ~ 65 years of gold ore processing in subarctic Canada

Climate change is profoundly affecting seasonality, biological productivity, and hydrology in high northern latitudes. In sensitive subarctic environments exploitation of mineral resources led to contamination and it is not known how cumulative effects of resource extraction and climate warming will impact ecosystems. Gold mines near Yellowknife, Northwest Territories, subarctic Canada, operated from 1938 to 2004 and released > 20,000 t of arsenic trioxide (As2O3) to the environment through stack emissions. This release resulted in elevated arsenic concentrations in lake surface waters and sediments relative to Canadian drinking water standards and guidelines for the protection of aquatic life. A meta-analytical approach is used to better understand controls on As distribution in lake sediments within a 30-km radius of historic mineral processing activities. Arsenic concentrations in the near-surface sediments range from 5 mg·kg− 1 to over 10,000 mg·kg− 1 (median 81 mg·kg− 1; n = 105). Distance and direction from the historic roaster stack are significantly (p < 0.05) related to sedimentary As concentration, with highest As concentrations in sediments within 11 km and lakes located downwind. Synchrotron-based μXRF and μXRD confirm the persistence of As2O3 in near surface sediments of two lakes. Labile organic matter (S1) is significantly (p < 0.05) related to As and S concentrations in sediments and this relationship is greatest in lakes within 11 km from the mine. These relations are interpreted to reflect labile organic matter acting as a substrate for microbial growth and mediation of authigenic precipitation of As-sulphides in lakes close to the historic mine where As concentrations are highest. Continued climate warming is expected to lead to increased biological productivity and changes in organic geochemistry of lake sediments that are likely to play an important role in the mobility and fate of As in aquatic ecosystems

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Automated Reporter Quantification In Vivo: High-Throughput Screening Method for Reporter-Based Assays in Zebrafish

Reporter-based assays underlie many high-throughput screening (HTS) platforms, but most are limited to in vitro applications. Here, we report a simple whole-organism HTS method for quantifying changes in reporter intensity in individual zebrafish over time termed, Automated Reporter Quantification in vivo (ARQiv). ARQiv differs from current “high-content” (e.g., confocal imaging-based) whole-organism screening technologies by providing a purely quantitative data acquisition approach that affords marked improvements in throughput. ARQiv uses a fluorescence microplate reader with specific detection functionalities necessary for robust quantification of reporter signals in vivo. This approach is: 1) Rapid; achieving true HTS capacities (i.e., >50,000 units per day), 2) Reproducible; attaining HTS-compatible assay quality (i.e., Z'-factors of ≥0.5), and 3) Flexible; amenable to nearly any reporter-based assay in zebrafish embryos, larvae, or juveniles. ARQiv is used here to quantify changes in: 1) Cell number; loss and regeneration of two different fluorescently tagged cell types (pancreatic beta cells and rod photoreceptors), 2) Cell signaling; relative activity of a transgenic Notch-signaling reporter, and 3) Cell metabolism; accumulation of reactive oxygen species. In summary, ARQiv is a versatile and readily accessible approach facilitating evaluation of genetic and/or chemical manipulations in living zebrafish that complements current “high-content” whole-organism screening methods by providing a first-tier in vivo HTS drug discovery platform

A mammalian functional-genetic approach to characterizing cancer therapeutics

Supplementary information is available online at http://www.nature.com/naturechemicalbiology/. Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/.Identifying mechanisms of drug action remains a fundamental impediment to the development and effective use of chemotherapeutics. Here we describe an RNA interference (RNAi)–based strategy to characterize small-molecule function in mammalian cells. By examining the response of cells expressing short hairpin RNAs (shRNAs) to a diverse selection of chemotherapeutics, we could generate a functional shRNA signature that was able to accurately group drugs into established biochemical modes of action. This, in turn, provided a diversely sampled reference set for high-resolution prediction of mechanisms of action for poorly characterized small molecules. We could further reduce the predictive shRNA target set to as few as eight genes and, by using a newly derived probability-based nearest-neighbors approach, could extend the predictive power of this shRNA set to characterize additional drug categories. Thus, a focused shRNA phenotypic signature can provide a highly sensitive and tractable approach for characterizing new anticancer drugs.National Institute of Mental Health (U.S.) (grant RO1 CA128803-03)American Association for Cancer ResearchMassachusetts Institute of Technology. Dept. of BiologyNational Cancer Institute (U.S.). Integrative Cancer Biology Program (grant 1-U54-CA112967

S100A6 (Calcyclin) is a prostate basal cell marker absent in prostate cancer and its precursors

S100A6 (Calcyclin) is a calcium-binding protein that has been implicated in a variety of biological functions as well as tumorigenesis. The aim of our study was to investigate the involvement of S100A6 during prostate cancer development and progression. Using immunohistochemistry, the expression of S100A6 was examined in benign (n ¼ 66), premalignant (n ¼ 10), malignant (n ¼ 66) and metastatic prostate (n ¼ 5) tissues arranged in a tissue-microarray or whole sections as well as in prostate cancer cell lines. The S100A6 immunostaining pattern in tissues was compared with that of cytokeratin 5 (a basal cell marker) and 18 (a benign luminal cell marker). In all cases of benign epithelium, intense S100A6 expression was seen in the basal cell layer with absent staining in luminal cells. In all cases of prostatic adenocarcinoma (matched), metastatic lesions and 3/10 high-grade prostatic intraepithelial neoplasia lesions, an absence of S100A6 was seen. Western blotting and RT–PCR analysis of cell lines showed S100A6 expression to be absent in LNCaP, LNCaP-LN3 and LNCaP-Pro5 but present in Du145, PC3, PC-3M and PC-3M-LN4. LNCaP cells treated with 5- Azacytidine, caused re-expression of S100A6 mRNA. Sequencing of bisulphite modified DNA showed CpG methylation within the S100A6 promoter region and exon 1 of LNCaP, LNCaP-LN3 and LNCaP-Pro5 cell lines but not in Du145 cells. Our data suggest that loss of S100A6 protein expression is common in prostate cancer development and may occur at an early stage. The mechanism of loss of expression may involve hypermethylation of CpG sites. The finding of intense S100A6 expression in the basal cells of benign glands but loss of expression in cancer could be useful as a novel diagnostic marker for prostate cancer

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets