Comparison of reproducibility, accuracy, sensitivity, and specificity of miRNA quantification platforms

Given the increasing interest in their use as disease biomarkers, the establishment of reproducible, accurate, sensitive, and specific platforms for microRNA (miRNA) quantification in biofluids is of high priority. We compare four platforms for these characteristics: small RNA sequencing (RNA-seq), FirePlex, EdgeSeq, and nCounter. For a pool of synthetic miRNAs, coefficients of variation for technical replicates are lower for EdgeSeq (6.9%) and RNA-seq (8.2%) than for FirePlex (22.4%); nCounter replicates are not performed. Receiver operating characteristic analysis for distinguishing present versus absent miRNAs shows small RNA-seq (area under curve 0.99) is superior to EdgeSeq (0.97), nCounter (0.94), and FirePlex (0.81). Expected differences in expression of placenta-associated miRNAs in plasma from pregnant and non-pregnant women are observed with RNA-seq and EdgeSeq, but not FirePlex or nCounter. These results indicate that differences in performance among miRNA profiling platforms impact ability to detect biological differences among samples and thus their relative utility for research and clinical use

Clustering, advection and patterns in a model of population dynamics with neighborhood-dependent rates

We introduce a simple model of population dynamics which considers birth and death rates for every individual that depend on the number of particles in its neighborhood. The model shows an inhomogeneous quasistationary pattern with many different clusters of particles. We derive the equation for the macroscopic density of particles, perform a linear stability analysis on it, and show that there is a finite-wavelength instability leading to pattern formation. This is the responsible for the approximate periodicity with which the clusters of particles arrange in the microscopic model. In addition, we consider the population when immersed in a fluid medium and analyze the influence of advection on global properties of the model.Comment: Some typos and some problems with the figures correcte

Atmospheric CO2 over the last 1000 years: A high-resolution record from the West Antarctic Ice Sheet (WAIS) Divide ice core

We report a decadally resolved record of atmospheric CO2 concentration for the last 1000 years, obtained from the West Antarctic Ice Sheet (WAIS) Divide shallow ice core. The most prominent feature of the pre‐industrial period is a rapid ∼7 ppm decrease of CO2 in a span of ∼20–50 years at ∼1600 A.D. This observation confirms the timing of an abrupt atmospheric CO2 decrease of ∼10 ppm observed for that time period in the Law Dome ice core CO2 records, but the true magnitude of the decrease remains unclear. Atmospheric CO2 variations over the time period 1000–1800 A.D. are statistically correlated with northern hemispheric climate and tropical Indo‐Pacific sea surface temperature. However, the exact relationship between CO2 and climate remains elusive due to regional climate variations and/or uneven geographical data density of paleoclimate records. We observe small differences of 0 ∼ 2% (0 ∼ 6 ppm) among the high‐precision CO2 records from the Law Dome, EPICA Dronning Maud Land and WAIS Divide Antarctic ice cores. However, those records share common trends of CO2 change on centennial to multicentennial time scales, and clearly show that atmospheric CO2 has been increasing above preindustrial levels since ∼1850 A.D

A 60 yr record of atmospheric carbon monoxide reconstructed from Greenland firn air

We present the first reconstruction of the Northern Hemisphere (NH) high latitude atmospheric carbon monoxide (CO) mole fraction from Greenland firn air. Firn air samples were collected at three deep ice core sites in Greenland (NGRIP in 2001, Summit in 2006 and NEEM in 2008). CO records from the three sites agree well with each other as well as with recent atmospheric measurements, indicating that CO is well preserved in the firn at these sites. CO atmospheric history was reconstructed back to the year 1950 from the measurements using a combination of two forward models of gas transport in firn and an inverse model. The reconstructed history suggests that Arctic CO in 1950 was 140–150 nmol mol-1, which is higher than today's values. CO mole fractions rose by 10–15 nmol mol-1 from 1950 to the 1970s and peaked in the 1970s or early 1980s, followed by a ˜ 30 nmol mol-1 decline to today's levels. We compare the CO history with the atmospheric histories of methane, light hydrocarbons, molecular hydrogen, CO stable isotopes and hydroxyl radicals (OH), as well as with published CO emission inventories and results of a historical run from a chemistry-transport model. We find that the reconstructed Greenland CO history cannot be reconciled with available emission inventories unless unrealistically large changes in OH are assumed. We argue that the available CO emission inventories strongly underestimate historical NH emissions, and fail to capture the emission decline starting in the late 1970s, which was most likely due to reduced emissions from road transportation in North America and Europe

A record of carbonyl sulfide from Antarctic ice over the last 1000 years

Carbonyl sulfide (COS) is a trace gas, present in the troposphere, and also in the stratosphere, where it contributes to the stratospheric sulfate aerosol layer. It has both natural and anthropogenic sources. Natural processes include uptake by plants, while oceans, wetlands, volcanism and biomass burning all contribute to natural COS emissions. We have measured COS in Antarctic ice cores from Dronning Maud Land, drilled in 1998, the DE08 core drilled at Law Dome in 1987, and the DSS0506 core drilled in 2006. Ice samples with COS gas ages between about 1050 AD and the early 20th centrury have been examined. A large volume ice crusher at the CSIRO Marine and Atmospheric Research laboratory was used to extract air from bubbles occluded in the ice cores. These air samples were analysed for CO2, CH4, CO and 13CO2 at CSIRO, and then for COS and several halocarbons at the University of East Anglia on a high sensitivity gas chromatograph/tri-sector mass spectrometer system. Initial results indicate that good sample integrity can be achieved. Measurements from the DML samples indicate low and uniform abundances across the last few hundred years, and at concentrations significantly below those in the modernday atmosphere. Measurements in more recent ice from DE08 show the start of increasing concentrations in the early 1900s, confirming earlier evidence that the global atmospheric abundance of COS has increased as a result of industrial activity during the 20th century

Phospho‐RNA‐seq: a modified small RNA‐seq method that reveals circulating mRNA and lncRNA fragments as potential biomarkers in human plasma

Extracellular RNAs (exRNAs) in biofluids have attracted great interest as potential biomarkers. Although extracellular microRNAs in blood plasma are extensively characterized, extracellular messenger RNA (mRNA) and long non‐coding RNA (lncRNA) studies are limited. We report that plasma contains fragmented mRNAs and lncRNAs that are missed by standard small RNA‐seq protocols due to lack of 5′ phosphate or presence of 3′ phosphate. These fragments were revealed using a modified protocol (“phospho‐RNA‐seq”) incorporating RNA treatment with T4‐polynucleotide kinase, which we compared with standard small RNA‐seq for sequencing synthetic RNAs with varied 5′ and 3′ ends, as well as human plasma exRNA. Analyzing phospho‐RNA‐seq data using a custom, high‐stringency bioinformatic pipeline, we identified mRNA/lncRNA transcriptome fingerprints in plasma, including tissue‐specific gene sets. In a longitudinal study of hematopoietic stem cell transplant patients, bone marrow‐ and liver‐enriched exRNA genes were tracked with bone marrow recovery and liver injury, respectively, providing proof‐of‐concept validation as a biomarker approach. By enabling access to an unexplored realm of mRNA and lncRNA fragments, phospho‐RNA‐seq opens up new possibilities for plasma transcriptomic biomarker development.SynopsisA modified RNA‐seq method (Phospho‐RNA‐seq) revealed a new population of mRNA/lncRNA fragments in plasma, including ones that track with disease. This opens up new possibilities for disease detection via RNA profiling of plasma and other biofluids.Phospho‐RNA‐seq reveals a large population of mRNA and long non‐coding RNA fragments in human plasma, which are missed by standard small RNA‐seq protocols that depend on target RNAs having a 5′ P and 3′ OH.Accurate detection of plasma mRNA and lncRNA fragments requires a stringent bioinformatic analysis pipeline to avoid false positive alignments to mRNA and lncRNA genes.Phospho‐RNA‐seq identified ensembles of tissue‐specific transcripts in plasma of hematopoietic stem cell transplant patients, which show co‐expression patterns that vary dynamically and track with pathophysiological processes.By enabling access to an unexplored space of extracellular mRNA and lncRNA fragments, phospho‐RNA‐seq opens up new possibilities for monitoring health and disease via transcriptome fragment profiling of plasma and potentially other biofluids.A modified RNA‐seq method reveals a large population of mRNA/lncRNA fragments in plasma that are missed by standard small RNA‐seq protocols including ones that are associated with disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149518/1/embj2019101695_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149518/2/embj2019101695-sup-0002-EVFigs.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149518/3/embj2019101695.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149518/4/embj2019101695-sup-0001-Appendix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149518/5/embj2019101695.reviewer_comments.pd

Possible charge inhomogeneities in the CuO2 planes of YBa2Cu3O6+x (x=0.25, 0.45, 0.65, 0.94) from pulsed neutron diffraction

The atomic pair distribution functions (PDF) of four powder samples of YBa2Cu3O6+x (x=0.25, 0.45, 0.65, 0.94) at 15 K have been measured by means of pulsed neutron diffraction. The PDF is modelled using a full-profile fitting approach to yield structural parameters. In contrast to earlier XAFS work we find no evidence of a split apical oxygen site. However, a slightly improved fit over the average crystallographic model results when the planar Cu(2) site is split along the z-direction. This is interpreted in terms of charge inhomogeneities in the CuO2 planes.Comment: 8 pages, 3 figure