Determination of Abundant Metabolite Matrix Adducts Illuminates the Dark Metabolome of MALDI-Mass Spectrometry Imaging Datasets

: Spatial metabolomics using mass spectrometry imaging (MSI) is a powerful tool to map hundreds to thousands of metabolites in biological systems. One major challenge in MSI is the annotation of m/z values, which is substantially complicated by background ions introduced throughout the chemicals and equipment used during experimental procedures. Among many factors, the formation of adducts with sodium or potassium ions, or in case of matrix-assisted laser desorption ionization (MALDI)- MSI, the presence of abundant matrix clusters strongly increases total m/z peak counts. Currently, there is a limitation to identify the chemistry of the many unknown peaks to interpret their biological function. We took advantage of the co-localization of adducts with their parent ions and the accuracy of high mass resolution to estimate adduct abundance in 20 datasets from different vendors of mass spectrometers. Metabolites ranging from lipids to amines and amino acids form matrix adducts with the commonly used 2,5-dihydroxybenzoic acid (DHB) matrix like [M + (DHB-H2O) + H]+ and [M + DHB + Na]+ . Current data analyses neglect those matrix adducts and overestimate total metabolite numbers, thereby expanding the number of unidentified peaks. Our study demonstrates that MALDI-MSI data are strongly influenced by adduct formation across different sample types and vendor platforms and reveals a major influence of so far unrecognized metabolite−matrix adducts on total peak counts (up to one third). We developed a software package, mass2adduct, for the community for an automated putative assignment and quantification of metabolite−matrix adducts enabling users to ultimately focus on the biologically relevant portion of the MSI data

Chest radiographs and machine learning - Past, present and future.

Despite its simple acquisition technique, the chest X-ray remains the most common first-line imaging tool for chest assessment globally. Recent evidence for image analysis using modern machine learning points to possible improvements in both the efficiency and the accuracy of chest X-ray interpretation. While promising, these machine learning algorithms have not provided comprehensive assessment of findings in an image and do not account for clinical history or other relevant clinical information. However, the rapid evolution in technology and evidence base for its use suggests that the next generation of comprehensive, well-tested machine learning algorithms will be a revolution akin to early advances in X-ray technology. Current use cases, strengths, limitations and applications of chest X-ray machine learning systems are discussed

Quantum Rotor Engines

This chapter presents autonomous quantum engines that generate work in the form of directed motion for a rotor. We first formulate a prototypical clock-driven model in a time-dependent framework and demonstrate how it can be translated into an autonomous engine with the introduction of a planar rotor degree of freedom. The rotor plays both the roles of internal engine clock and of work repository. Using the example of a single-qubit piston engine, the thermodynamic performance is then reviewed. We evaluate the extractable work in terms of ergotropy, the kinetic energy associated to net directed rotation, as well as the intrinsic work based on the exerted torque under autonomous operation; and we compare them with the actual energy output to an external dissipative load. The chapter closes with a quantum-classical comparison of the engine's dynamics. For the single-qubit piston example, we propose two alternative representations of the qubit in an entirely classical framework: (i) a coin flip model and (ii) a classical magnet moment, showing subtle differences between the quantum and classical descriptions.Comment: Chapter of the upcoming book "Thermodynamics in the Quantum Regime - Recent Progress and Outlook

Framing and signalling effects of taxes on sugary drinks: a discrete choice experiment among households in Great Britain

Taxes on sugar-sweetened beverages (SSBs) are in place in many countries to combat obesity with emerging evidence that these are effective in reducing purchases of SSBs. In this study, we tested whether signalling and framing the price increase from an SSB tax explicitly as a health-related, earmarked measure reduces the demand for SSBs more than an equivalent price increase. We measured the demand for non-alcoholic beverages with a discrete choice experiment (DCE) administered online to a randomly selected group of n = 603 households with children in Great Britain (GB) who regularly purchase SSBs. We find a suggestive evidence that a price increase leads to a larger reduction in the probability of choosing SSBs when it is signalled as a tax and framed as a health-related and earmarked policy. Respondents who did not support a tax on SSBs, who were also more likely to choose SSBs in the first place, were on average more responsive to a price increase framed as an earmarked tax than those who supported the tax. The predictive validity of the DCE, to capture preferences for beverages, was confirmed using actual purchase data. The findings imply that a well-signalled and earmarked tax on SSBs could improve its effectiveness at reducing the demand

A genome-wide RNAi screen identifies factors required for distinct stages of C-elegans piRNA biogenesis

In animals, piRNAs and their associated Piwi proteins guard germ cell genomes against mobile genetic elements via an RNAi-like mechanism. In Caenorhabditis elegans, 21U-RNAs comprise the piRNA class, and these collaborate with 22G RNAs via unclear mechanisms to discriminate self from nonself and selectively and heritably silence the latter. Recent work indicates that 21U-RNAs are post-transcriptional processing products of individual transcription units that produce similar to 26-nucleotide capped precursors. However, nothing is known of how the expression of precursors is controlled or how primary transcripts give rise to mature small RNAs. We conducted a genome-wide RNAi screen to identify components of the 21U biogenesis machinery. Screening by direct, quantitative PCR (qPCR)-based measurements of mature 21U-RNA levels, we identified 22 genes important for 21U-RNA production, termed TOFUs (Twenty-One-u Fouled Ups). We also identified seven genes that normally repress 21U production. By measuring mature 21U-RNA and precursor levels for the seven strongest hits from the screen, we assigned factors to discrete stages of 21U-RNA production. Our work identifies for the first time factors separately required for the transcription of 21U precursors and the processing of these precursors into mature 21U-RNAs, thereby providing a resource for studying the biogenesis of this important small RNA class

Evolution of spectral function in a doped Mott insulator : surface vs. bulk contributions

We study the evolution of the spectral function with progressive hole doping in a Mott insulator, $La_{1-x}Ca_xVO_3$ with $x$ = 0.0 - 0.5. The spectral features indicate a bulk-to-surface metal-insulator transition in this system. Doping dependent changes in the bulk electronic structure are shown to be incompatible with existing theoretical predictions. An empirical description based on the single parameter, $U/W$, is shown to describe consistently the spectral evolution.Comment: Revtex, 4 pages, 3 postscript figures. To appear in Phys. Rev. Let

Accreting coral reefs in a highly urbanized environment

Globally, many coral reefs have fallen into negative carbonate budget states, where biological erosion exceeds carbonate production. The compounding effects of urbanization and climate change have caused reductions in coral cover and shifts in community composition that may limit the ability of reefs to maintain rates of vertical accretion in line with rising sea levels. Here we report on coral reef carbonate budget surveys across seven coral reefs in Singapore, which persist under chronic turbidity and in highly disturbed environmental conditions, with less than 20% light penetration to 2 m depth. Results show that mean net carbonate budgets across Singapore’s reefs were relatively low, at 0.63 ± 0.27 kg CaCO3 m−2 yr−1 (mean ± 1 SE) with a range from − 1.56 to 1.97, compared with the mean carbonate budgets across the Indo-Pacific of 1.4 ± 0.15 kg CaCO3 m−2 yr−1, and isolated Indian Ocean reefs pre-2016 bleaching (~ 3.7 kg CaCO3 m−2 yr−1). Of the seven reefs surveyed, only one reef had a net negative, or erosional budget, due to near total loss of coral cover (\u3c 5% remaining coral). Mean gross carbonate production on Singapore’s reefs was dominated by stress-tolerant and generalist species, with low-profile morphologies, and was ~ 3 kg m−2 yr−1 lower than on reefs with equivalent coral cover elsewhere in the Indo-Pacific. While overall these reefs are maintaining and adding carbonate structure, their mean vertical accretion potential is below both current rates of sea level rise (1993–2010), and future predictions under RCP 4.5 and RCP 8.5 scenarios. This is likely to result in an increase of 0.2–0.6 m of water above Singapore’s reefs in the next 80 yr, further narrowing the depth range over which these reefs can persist

Sulfur-Oxidizing Symbionts without Canonical Genes for Autotrophic CO2 Fixation

Many animals and protists depend on symbiotic sulfur-oxidizing bacteria as their main food source. These bacteria use energy from oxidizing inorganic sulfur compounds to make biomass autotrophically from CO2, serving as primary producers for their hosts. Here we describe a clade of nonautotrophic sulfur-oxidizing symbionts, “Candidatus Kentron,” associated with marine ciliates. They lack genes for known autotrophic pathways and have a carbon stable isotope fingerprint heavier than other symbionts from similar habitats. Instead, they have the potential to oxidize sulfur to fuel the uptake of organic compounds for heterotrophic growth, a metabolic mode called chemolithoheterotrophy that is not found in other symbioses. Although several symbionts have heterotrophic features to supplement primary production, in Kentron they appear to supplant it entirely.Since the discovery of symbioses between sulfur-oxidizing (thiotrophic) bacteria and invertebrates at hydrothermal vents over 40 years ago, it has been assumed that autotrophic fixation of CO2 by the symbionts drives these nutritional associations. In this study, we investigated “Candidatus Kentron,” the clade of symbionts hosted by Kentrophoros, a diverse genus of ciliates which are found in marine coastal sediments around the world. Despite being the main food source for their hosts, Kentron bacteria lack the key canonical genes for any of the known pathways for autotrophic carbon fixation and have a carbon stable isotope fingerprint that is unlike other thiotrophic symbionts from similar habitats. Our genomic and transcriptomic analyses instead found metabolic features consistent with growth on organic carbon, especially organic and amino acids, for which they have abundant uptake transporters. All known thiotrophic symbionts have converged on using reduced sulfur to gain energy lithotrophically, but they are diverse in their carbon sources. Some clades are obligate autotrophs, while many are mixotrophs that can supplement autotrophic carbon fixation with heterotrophic capabilities similar to those in Kentron. Here we show that Kentron bacteria are the only thiotrophic symbionts that appear to be entirely heterotrophic, unlike all other thiotrophic symbionts studied to date, which possess either the Calvin-Benson-Bassham or the reverse tricarboxylic acid cycle for autotrophy

Fermi-surface reconstruction involving two Van Hove singularities across the antiferromagnetic transition in BaFe2As2

We report an angle-resolved photoemission study of BaFe2As2, a parent compound of iron-based superconductors. Low-energy tunable excitation photons have allowed the first observation of a saddle-point singularity at the Z point, as well as the Gamma point. With antiferromagnetic ordering, both of these two van Hove singularities come down below the Fermi energy, leading to a topological change in the innermost Fermi surface around the kz axis from cylindrical to tear-shaped, as expected from first-principles calculation. These singularities may provide an additional instability for the Fermi surface of the superconductors derived from BaFe2As2.Comment: 14 pages, 4 figures, 1 tabl