KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells

<p>Abstract</p> <p>Background</p> <p>Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally through the binding of the <it>trans-</it>acting proteins AU rich binding factor 1 (AUF1), Upstream of N-<it>ras </it>(Unr) and KH-type splicing regulatory protein (KSRP) to an AU rich element (ARE) in PTH mRNA 3'-UTR. AUF1 and Unr stabilize PTH mRNA while KSRP, recruiting the exoribonucleolytic complex exosome, promotes PTH mRNA decay.</p> <p>Results</p> <p>PTH mRNA is cleaved by the endoribonuclease polysomal ribonuclease 1 (PMR1) in an ARE-dependent manner. Moreover, PMR1 co-immunoprecipitates with PTH mRNA, the exosome and KSRP. Knock-down of either exosome components or KSRP by siRNAs prevents PMR1-mediated cleavage of PTH mRNA.</p> <p>Conclusion</p> <p>PTH mRNA is a target for the endonuclease PMR1. The PMR1 mediated decrease in PTH mRNA levels involves the PTH mRNA 3'-UTR ARE, KSRP and the exosome. This represents an unanticipated mechanism by which the decay of an ARE-containing mRNA is facilitated by KSRP and is dependent on both the exosome and an endoribonuclease.</p

A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5′cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T is a nucleocytoplasmic shuttling protein, which mediates the import of eIF4E into the nucleus. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described processing bodies (P-bodies), which are believed to be sites of mRNA decay. In this paper, we demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies. Moreover, 4E-T controls mRNA half-life, because its depletion from cells using short interfering RNA increases mRNA stability. The 4E-T binding partner, eIF4E, also is localized in P-bodies. 4E-T interaction with eIF4E represses translation, which is believed to be a prerequisite for targeting of mRNAs to P-bodies. Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay

Sequential approach to joint flow-seismic inversion for improved characterization of fractured media

Seismic interpretation of subsurface structures is traditionally performed without any account of flow behavior. Here we present a methodology for characterizing fractured geologic reservoirs by integrating flow and seismic data. The key element of the proposed approach is the identification—within the inversion—of the intimate relation between fracture compliance and fracture transmissivity, which determine the acoustic and flow responses of a fractured reservoir, respectively. Owing to the strong (but highly uncertain) dependence of fracture transmissivity on fracture compliance, the modeled flow response in a fractured reservoir is highly sensitive to the geophysical interpretation. By means of synthetic models, we show that by incorporating flow data (well pressures and tracer breakthrough curves) into the inversion workflow, we can simultaneously reduce the error in the seismic interpretation and improve predictions of the reservoir flow dynamics. While the inversion results are robust with respect to noise in the data for this synthetic example, the applicability of the methodology remains to be tested for more complex synthetic models and field cases.Eni-MIT Energy Initiative Founding Member ProgramKorea (South). Ministry of Land, Transportation and Maritime Affairs (15AWMP-B066761-03

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Innovative Visualizations Shed Light on Avian Nocturnal Migration

We acknowledge the support provided by COST–European Cooperation in Science and Technology through the Action ES1305 ‘European Network for the Radar Surveillance of Animal Movement’ (ENRAM) in facilitating this collaboration. We thank ENRAM members and researchers attending the EOU round table discussion ‘Radar aeroecology: unravelling population scale patterns of avian movement’ for feedback on the visualizations. We thank Arie Dekker for his feedback as jury member of the bird migration visualization challenge & hackathon hosted at the University of Amsterdam, 25–27 March 2015. We thank Willem Bouten and Kevin Winner for discussion of methodological design. We thank Kevin Webb and Jed Irvine for assistance with downloading, managing, and reviewing US radar data. We thank the Royal Meteorological Institute of Belgium for providing weather radar data.Globally, billions of flying animals undergo seasonal migrations, many of which occur at night. The temporal and spatial scales at which migrations occur and our inability to directly observe these nocturnal movements makes monitoring and characterizing this critical period in migratory animals’ life cycles difficult. Remote sensing, therefore, has played an important role in our understanding of large-scale nocturnal bird migrations. Weather surveillance radar networks in Europe and North America have great potential for long-term low-cost monitoring of bird migration at scales that have previously been impossible to achieve. Such long-term monitoring, however, poses a number of challenges for the ornithological and ecological communities: how does one take advantage of this vast data resource, integrate information across multiple sensors and large spatial and temporal scales, and visually represent the data for interpretation and dissemination, considering the dynamic nature of migration? We assembled an interdisciplinary team of ecologists, meteorologists, computer scientists, and graphic designers to develop two different flow visualizations, which are interactive and open source, in order to create novel representations of broad-front nocturnal bird migration to address a primary impediment to long-term, large-scale nocturnal migration monitoring. We have applied these visualization techniques to mass bird migration events recorded by two different weather surveillance radar networks covering regions in Europe and North America. These applications show the flexibility and portability of such an approach. The visualizations provide an intuitive representation of the scale and dynamics of these complex systems, are easily accessible for a broad interest group, and are biologically insightful. Additionally, they facilitate fundamental ecological research, conservation, mitigation of human–wildlife conflicts, improvement of meteorological products, and public outreach, education, and engagement.Yeshttp://www.plosone.org/static/editorial#pee