Dynamic range and mass accuracy of wide-scan direct infusion nanoelectrospray fourier transform ion cyclotron resonance mass spectrometry-based metabolomics increased by the spectral stitching method

Direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry (DI nESI FT-ICR MS)offers high mass accuracy and resolution for analyzing complex metabolite mixtures. High dynamic range across a wide mass range, however, can only be achieved at the expense of mass accuracy, since the large numbers of ions entering the ICR detector induce adverse spacecharge effects. Here we report an optimized strategy for wide-scan DI nESI FT-ICR MS that increases dynamic range but maintains high mass accuracy. It comprises the collection if multiple adjacent selected ion monitoring (SIM) windows that are stitched together using novel algorithms. The final SIM-stitching method, derived from several optimization experiments, comprises 21 adjoining SIM windows each of width m/z 30 (from m/z 70 to 500; adjacent windows overlap by m/z 10) with an automated gain control (AGC) target of 1 105 charges. SIMstitching and wide-scan range (WSR; Thermo Electron)were compared using a defined standard to assess mass accuracy and a liver extract to assess peak count and dynamic range. SIM-stitching decreased the maximum mass error by 1.3- and 4.3-fold, and increased the peak count by 5.3- and 1.8-fold, versus WSR (AGC targets of 1 x 105 and 5 x 105, respectively). SIM-stitching achieved an rms mass error of 0.18 ppm and detected over 3000 peaks in liver extract. This novel approach increases metabolome coverage, has very high mass accuracy, and at 5.5 min/sample is conducive for high- throughput metabolomics

An infrared study of modern and paleo-filamentous bacteria from Rio Tinto, Spain

The Rio Tinto River Basin in southwestern Spain is a natural acidic (pH ~2.3) drainage system that supports a diversity of acid tolerant bacteria and eukaryotes with iron and sulfur- oxidizing prokaryotes performing chemolithotrophy and supporting anaerobic respiration [1, 2]. River terrace deposits formed over the past 2 Myr have preserved remnants of this unique biosphere, particularly microbial filaments, which provide templates for iron sulphate and iron oxide precipitation [1, 2]. This process of permineralization causes organic material to become trapped within a mineral matrix and preserved over geological time. This study analysed cultured filamentous bacteria, modern biofilms and sediments, and river terrace deposits spanning 2.1 Myr to assess the preservation of organics in this extreme environment over time, and the ability to correlate them with a contemporary culture. Filamentous bacteria are preserved within optically translucent nanophase to crystalline jarosite and goethite within all samples. The cultures contained 1 μm diameter filaments, some partially encrusted with iron oxides with visible cell walls, and others completely free of iron oxides, that are morphologically comparable to those preserved in the Rio Tinto rock record. Organic compounds (e.g. aliphatic hydrocarbons, amides and carboxylic acids) were detected at various levels within the culture and river terraces using mid-IR spectroscopy. Rio Tinto is a natural laboratory allowing living cells to be studied and correlated to morphological and biomolecular fossils in the geological record. These deposits will provide predictive tools for biomarker studies that may be extended to analogous environments on ancient Earth or even Mars. [1] Fernández-Remolar et al. (2005) Earth Planet Sci Lett 240,149-167. [2] Fernández-Remolar & Knoll (2008) Icarus 194,72-85

Organic Matter Preservation and Incipient Mineralization of Microtubules in 120 Ma Basaltic Glass

Hollow tubular structures in subaqueously-emplaced basaltic glass may represent trace fossils caused by microbially-mediated glass dissolution. Mineralized structures of similar morphology and spatial distribution in ancient, metamorphosed basaltic rocks have widely been interpreted as ichnofossils, possibly dating to similar to 3.5 Ga or greater. Doubts have been raised, however, regarding the biogenicity of the original hollow tubules and granules in basaltic glass. In particular, although elevated levels of biologically-important elements such as C, S, N, and P as well as organic compounds have been detected in association with these structures, a direct detection of unambiguously biogenic organic molecules has not been accomplished. In this study, we describe the direct detection of proteins associated with tubular textures in basaltic glass using synchrotron X-ray spectromicroscopy. Protein-rich organic matter is shown to be associated with the margins of hollow and partly-mineralized tubules. Furthermore, a variety of tubule-infilling secondary minerals, including Ti-rich oxide phases, were observed filling and preserving the microtextures, demonstrating a mechanism whereby cellular materials may be preserved through geologic time

‘Imposter participants’ in online qualitative research, a new and increasing threat to data integrity?

Letter to the Editor: Health Expectation

ADOLESCENT AMENORRHEA

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73937/1/j.1749-6632.1967.tb14694.x.pd

Biogeochemical cycling of silver in acidic, weathering environments

Under acidic, weathering conditions, silver (Ag) is considered to be highly mobile and can be dispersed within near-surface environments. In this study, a range of regolith materials were sampled from three abandoned open pit mines located in the Iberian Pyrite Belt, Spain. Samples were analyzed for Ag mineralogy, content, and distribution using micro-analytical techniques and high-resolution electron microscopy. While Ag concentrations were variable within these materials, elevated Ag concentrations occurred in gossans. The detection of Ag within younger regolith materials, i.e., terrace iron formations and mine soils, indicated that Ag cycling was a continuous process. Microbial microfossils were observed within crevices of gossan and their presence highlights the preservation of mineralized cells and the potential for biogeochemical processes contributing to metal mobility in the rock record. An acidophilic, iron-oxidizing microbial consortium was enriched from terrace iron formations. When the microbial consortium was exposed to dissolved Ag, more than 90% of Ag precipitated out of solution as argentojarosite. In terms of biogeochemical Ag cycling, this demonstrates that Ag re-precipitation processes may occur rapidly in comparison to Ag dissolution processes. The kinetics of Ag mobility was estimated for each type of regolith material. Gossans represented 0.6–146.7 years of biogeochemical Ag cycling while terrace iron formation and mine soils represented 1.9–42.7 years and 0.7–1.6 years of Ag biogeochemical cycling, respectively. Biogeochemical processes were interpreted from the chemical and structural characterization of regolith material and demonstrated that Ag can be highly dispersed throughout an acidic, weathering environment.Jeremiah Shuster, Frank Reith, Matthew R. M. Izawa, Roberta L. Flemming, Neil R. Banerjee and Gordon Southa

Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

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A molecular map of long non-coding RNA expression, isoform switching and alternative splicing in osteoarthritis

Osteoarthritis is a prevalent joint disease and a major cause of disability worldwide with no curative therapy. Development of disease-modifying therapies requires a better understanding of the molecular mechanisms underpinning disease. A hallmark of osteoarthritis is cartilage degradation. To define molecular events characterizing osteoarthritis at the whole transcriptome level, we performed deep RNA sequencing in paired samples of low- and high-osteoarthritis grade knee cartilage derived from 124 patients undergoing total joint replacement. We detected differential expression between low- and high-osteoarthritis grade articular cartilage for 365 genes and identified a 38-gene signature in osteoarthritis cartilage by replicating our findings in an independent dataset. We also found differential expression for 25 novel long non-coding RNA genes (lncRNAs) and identified potential lncRNA interactions with RNA-binding proteins in osteoarthritis. We assessed alterations in the relative usage of individual gene transcripts and identified differential transcript usage for 82 genes, including ABI3BP, coding for an extracellular matrix protein, AKT1S1, a negative regulator of the mTOR pathway and TPRM4, coding for a transient receptor potential channel. We further assessed genome-wide differential splicing, for the first time in osteoarthritis, and detected differential splicing for 209 genes, which were enriched for extracellular matrix, proteoglycans and integrin surface interactions terms. In the largest study of its kind in osteoarthritis, we find that isoform and splicing changes, in addition to extensive differences in both coding and non-coding sequence expression, are associated with disease and demonstrate a novel layer of genomic complexity to osteoarthritis pathogenesis