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The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics., Here, the authors apply DESI-MS, a sample preparation-free, direct on-swab mass spectrometry analytical tool, to profile the cervicovaginal metabolome of two independent cohorts of pregnant women and, combined with matched metataxonomic and immuno-profiling data, show that DESI-MS predicts vaginal microbiota composition and local inflammatory status associated with preterm birth and clinical interventions used during pregnancy.

Single-cell analysis provides insights into cellular heterogeneity and dynamics of individual cells. This feature highlights recent developments in key analytical techniques suited for single-cell metabolic analysis with a special focus on mass spectrometry-based analytical platforms and RNA-seq, as well as imaging techniques that reveal stochasticity in metabolism.

Electrospray ionization (ESI) mass spectrometry (MS) is used to study the non-covalent interactions of short 12-mer oligonucleotides under native conditions. A home-built, temperature-controlled ESI source is employed to elevate the spray temperature above the melting temperature (T-m) of the DNA duplexes, enabling the study of DNA interactions in the liquid phase rather than gas phase. Ion mobility spectrometry (IMS)-MS is used to investigate the 3-dimensional structure of the hybridized oligonucleotides and to track conformational changes in the oligonucleotide duplexes during temperature-induced melting in solution. Results show two additional drift times at T > 35 degrees C, indicating 2-fold (partial) unfolding dynamics for the DNA duplex with stable intermediates. (C) 2017 Elsevier B.V. All rights reserved.

Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-for-purpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires 10 000 24 h urine samples from the INTERMAP study in 12 weeks and >2200 spot urine samples from the ARIC study in

Ambient ionization-based techniques hold great potential for rapid point-of-care applicable metabolic fingerprinting of tissue and fluids. Hereby, feces represents a unique biospecimen as it integrates the complex interactions between the diet, gut microbiome and host, and is therefore ideally suited to study the involvement of the diet-gut microbiome axis in metabolic diseases and their treatments at a molecular level. We present a new method for rapid (

Due to its multifunctional and complex role in the honey bee colony functioning and health (construction material allowing food storage, brood rearing, thermoregulation, mediation in chemical and mechanical communication, substrate for pathogens, toxins and waste), Apis mellifera beeswax has been widely studied over the last five decades. This is supported by a comprehensive set of scientific reports covering different aspects of beeswax research. In this article, we present an overview of the methods for studying chemical, biological, constructional, and quality aspects of beeswax. We provide a detailed description of the methods for investigating wax scales, comb construction and growth pattern, cell properties, chemical composition of beeswax using different analytical tools, as well as the analytical procedures for provenancing beeswax and beeswax-derived compounds based on the hydrogen isotope ratio (IRMS). Along with classical physico-chemical and sensory analysis, we describe more precise and accurate methods for detection of adulterants in beeswax (GC-MS and FTIR-ATR). Moreover, we present methods for studying the influence of beeswax (comb foundation) adulteration on comb construction. Analytical protocols for determining the pesticide residues using different chromatographic and spectroscopic techniques are also described. As beeswax is an agent of high risk for the transmission of bee diseases, we present methods for detection of pathogens in beeswax. To ensure the reproducibility of experiments and results, we present best practice approaches and detailed protocols for all methods described, as well as their advantages and disadvantages. COST ActionEuropean Cooperation in Science and Technology (COST) [FA0803]; Ricola Foundation - Nature Culture We would like to acknowledge the Ricola Foundation - Nature & Culture, and COST Action FA0803 for funding the COLOSS (Prevention of honey bee COlony LOSSes) network and making the BEEBOOK possible. We would also like to express our gratitude to Editor Vincent Dietemann for his kind support all the way, and for providing helpful and constructive suggestions.

Heterogeneous uptake of dinitrogen pentoxide (N2O5) and production of nitryl chloride (ClNO2) are important nocturnal atmospheric processes that have significant implications for the production of secondary pollutants. However, the understanding of N2O5 uptake processes and ClNO2 production remains limited, especially in China. This study presents a field investigation of the N2O5 heterogeneous uptake coefficient (γ(N2O5)) and ClNO2 production yield (ϕ) in a polluted area of northern China during the summer of 2014. The N2O5 uptake coefficient and ClNO2 yield were estimated by using the simultaneously measured ClNO2 and total nitrate in 10 selected cases, which have concurrent increases in the ClNO2 and nitrate concentrations and relatively stable environmental conditions. The determined γ(N2O5) and ϕ values varied greatly, with an average of 0.022 for γ(N2O5) (±0.012, standard deviation) and 0.34 for ϕ (±0.28, standard deviation). The variations in γ(N2O5) could not be fully explained by the previously derived parameterizations of N2O5 uptake that consider nitrate, chloride, and the organic coating. Heterogeneous uptake of N2O5 was found to have a strong positive dependence on the relative humidity and aerosol water content. This result suggests that the heterogeneous uptake of N2O5 in Wangdu is governed mainly by the amount of water in the aerosol, and is strongly water limited, which is different from most of the field observations in the US and Europe. The ClNO2 yield estimated from the parameterization was also overestimated comparing to that derived from the observation. The observation-derived ϕ showed a decreasing trend with an increasing ratio of acetonitrile to carbon monoxide, an indicator of biomass burning emissions, which suggests a possible suppressive effect on the production yield of ClNO2 in the plumes influenced by biomass burning in this region. The findings of this study illustrate the need to improve our understanding and to parameterize the key factors for γ(N2O5) and ϕ to accurately assess photochemical and haze pollution.

Recent developments in the field of ion mobility spectrometry provide new possibilities to explore and understand gas-phase ion chemistry. In this study, hyphenated trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) was applied to investigate analyte ion mobility as function of adduct ion formation for twelve pharmaceutically relevant molecules, and for tetrahydrocannabinol (THC) and its isomer cannabidiol (CBD). Samples were introduced by direct infusion and ions were generated with positive electrospray ionization (ESI+) observing protonated and sodiated ions. Measurements were performed with and without addition of cesium-, lithium-, silver- and sodium ions to the samples. For the tested compounds, metal adduct ions with the same m/z but with different mobility and collision cross section (CCSs) were observed, indicating different molecular conformations. Formation of analyte dimers was also observed, which could be associated with molecular geometry of the compounds. By optimizing the range and speed of the electric field gradient and ramp, respectively, the separation of THC and CBD was achieved by employing the adduct formation. This study demonstrates that the favorable resolution of TIMS combined with the ability to detect weakly bound counter ions is a valuable means for rapid detection, separation and structural assignment of molecular isomers and analyte conformations.

International audience; Moniliformin (MON) is a mycotoxin with low molecular weight primarily produced by Fusarium fungi and occurring predominantly in cereal grains. Following a request of the European Commission, the CONTAM Panel assessed the risk of MON to human and animal health related to its presence in food and feed. The limited information available on toxicity and on toxicokinetics in experimental and farm animals indicated haematotoxicity and cardiotoxicity as major adverse health effects of MON. MON causes chromosome aberrations in vitro but no in vivo genotoxicity data and no carcinogenicity data were identified. Due to the limitations in the available toxicity data, human acute or chronic health-based guidance values (HBGV) could not be established. The margin of exposure (MOE) between the no-observed-adverse-effect level (NOAEL) of 6.0 mg/kg body weight (bw) for cardiotoxicity from a subacute study in rats and the acute upper bound (UB) dietary exposure estimates ranged between 4,000 and 73,000. The MOE between the lowest benchmark dose lower confidence limit (for a 5% response-BMDL 05) of 0.20 mg MON/kg bw per day for haematological hazards from a 28-day study in pigs and the chronic dietary human exposure estimates ranged between 370 and 5,000,000 for chronic dietary exposures. These MOEs indicate a low risk for human health but were associated with high uncertainty. The toxicity data available for poultry, pigs, and mink indicated a low or even negligible risk for these animals from exposure to MON in feed at the estimated exposure levels under current feeding practices. Assuming similar or lower sensitivity as for pigs, the CONTAM Panel considered a low or even negligible risk for the other animal species for which no toxicity data suitable for hazard characterisation were identified. Additional toxicity studies are needed and depending on their outcome, the collection of more occurrence data on MON in food and feed is recommended to enable a comprehensive human risk assessment.

The chemistry of aluminum or oxo-aluminum in water is still relatively unknown, although it is the basis for many chemical and industrial processes, including flocculation in water treatment plants. Trimeric species have a predominant role in the formation of the Keggin cations, which are the basic building blocks of aluminum-based chemicals. Despite this, details of the structural evolution of these small solvated clusters and how this is related to the processes leading to the formation of larger aggregates are still an open issue. To address these questions, here, we have applied the metadynamics (MTD) simulation technique [ Barducci , A. ; Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2010 , 1 , 826 - 843 ] with density functional theory-based molecular dynamics to disclose the dynamics and structural conversions of trimeric aluminum complexes in an aqueous environment. The existence of a variety of competing metastable conformations, for example, book-like, cyclic boat, and linear shape conformations, is revealed in the MTD simulation. Furthermore, equilibrium simulations of the various intermediate states encountered along the MTD trajectory are used to assess their (meta)stability, determine the rearrangement of the OH ligands, and discuss the role of the solvating water.

Atmospheric oxidation is an important phenomenon which produces large quantities of low-volatility compounds such as sulfuric acid and oxidized organic compounds. Such species may be involved in the nucleation of particles and enhance their subsequent growth to reach the size of cloud condensation nuclei (CCN). In this study, we investigate α-pinene, the most abundant monoterpene globally, and its oxidation products formed through ozonolysis in the Cosmic Leaving OUtdoor Droplets (CLOUD) chamber at CERN (the European Organization for Nuclear Research). By scavenging hydroxyl radicals (OH) with hydrogen (H2), we were able to investigate the formation of highly oxygenated molecules (HOMs) purely driven by ozonolysis and study the oxidation of sulfur dioxide (SO2) driven by stabilized Criegee intermediates (sCIs). We measured the concentrations of HOM and sulfuric acid with a chemical ionization atmospheric-pressure interface time-of-flight (CI-APi-TOF) mass spectrometer and compared the measured concentrations with simulated concentrations calculated with a kinetic model. We found molar yields in the range of 3.5–6.5 % for HOM formation and 22–32 % for the formation of stabilized Criegee intermediates by fitting our model to the measured sulfuric acid concentrations. The simulated time evolution of the ozonolysis products was in good agreement with measured concentrations except that in some of the experiments sulfuric acid formation was faster than simulated. In those experiments the simulated and measured concentrations met when the concentration reached a plateau but the plateau was reached 20–50 min later in the simulations. The results shown here are consistent with the recently published yields for HOM formation from different laboratory experiments. Together with the sCI yields, these results help us to understand atmospheric oxidation processes better and make the reaction parameters more comprehensive for broader use.

Oxidation flow reactors that use low-pressure mercury lamps to produce hydroxyl (OH) radicals are an emerging technique for studying the oxidative aging of organic aerosols. Here, ozone (O-3) is photolyzed at 254 nm to produce O(D-1) radicals, which react with water vapor to produce OH. However, the need to use parts-per-million levels of O-3 hinders the ability of oxidation flow reactors to simulate NOx-dependent secondary organic aerosol (SOA) formation pathways. Simple addition of nitric oxide (NO) results in fast conversion of NOx (NO + NO2) to nitric acid (HNO3), making it impossible to sustain NOx at levels that are sufficient to compete with hydroperoxy (HO2) radicals as a sink for organic peroxy (RO2) radicals. We developed a new method that is well suited to the characterization of NOx-dependent SOA formation pathways in oxidation flow reactors. NO and NO2 are produced via the reaction O(D-1) + N2O -> 2NO, followed by the reaction NO + O-3 -> NO2 + O-2. Laboratory measurements coupled with photochemical model simulations suggest that O(D-1) + N2O reactions can be used to systematically vary the relative branching ratio of RO2 + NO reactions relative to RO2 + HO2 and/or RO2 + RO2 reactions over a range of conditions relevant to atmospheric SOA formation. We demonstrate proof of concept using high-resolution time-of-flight chemical ionization mass spectrometer (HR-ToF-CIMS) measurements with nitrate (NO3-) reagent ion to detect gas-phase oxidation products of isoprene and alpha-pinene previously observed in NOx-influenced environments and in laboratory chamber experiments.

We present ambient observations of dimeric monoterpene oxidation products (C16-20HyO6-9) in gas and particle phases in the boreal forest in Finland in spring 2013 and 2014, detected with a chemical ionization mass spectrometer with a filter inlet for gases and aerosols employing acetate and iodide as reagent ions. These are among the first online dual-phase observations of such dimers in the atmosphere. Estimated saturation concentrations of 10(-15) to 10(-6)mu gm(-3) (based on observed thermal desorptions and group-contribution methods) and measured gas-phase concentrations of 10(-3) to 10(-2)mu gm(-3) (similar to 10(6)-10(7)moleculescm(-3)) corroborate a gas-phase formation mechanism. Regular new particle formation (NPF) events allowed insights into the potential role dimers may play for atmospheric NPF and growth. The observationally constrained Model for Acid-Base chemistry in NAnoparticle Growth indicates a contribution of similar to 5% to early stage particle growth from the similar to 60 gaseous dimer compounds. Plain Language Summary Atmospheric aerosol particles influence climate and air quality. We present new insights into how emissions of volatile organic compounds from trees are transformed in the atmosphere to contribute to the formation and growth of aerosol particles. We detected for the first time over a forest, a group of organic molecules, known to grow particles, in the gas phase at levels far higher than expected. Previous measurements had only measured them in the particles. This finding provides guidance on how models of aerosol formation and growth should describe their appearance and fate in the atmosphere.

The isoflavonoid composition of an ethanolic extract of fungus-treated soybean sprouts was strongly altered by a combined acid/heat treatment. UHPLC-MS analysis showed that 6a-hydroxy-pterocarpans were completely converted to their respective, more stable, 6a,11a-pterocarpenes, whereas other isoflavonoids, from the isoflavone and coumestan subclasses, were affected to a much lesser extent (loss of ~15%). Subsequently, mixtures enriched in prenylated 6a-hydroxy-pterocarpans (pools of glyceollin I/II/III and glyceollin IV/VI) or prenylated 6a,11a-pterocarpenes (pools of dehydroglyceollin I/II/III and dehydroglyceollin IV/VI) were purified, and tested for activity on both human estrogen receptors (ERa and ERß). In particular, the response toward ERa changed, from agonistic for glyceollins to antagonistic for dehydroglyceollins. Toward ERß a decrease in agonistic activity was observed. These results indicate that the introduction of a double bond with the concomitant loss of a hydroxyl group in 6a-hydroxy-pterocarpans extensively modulates their estrogenic activity.

Many studies on the molecular control underlying normal cell behavior and cellular responses to disease stimuli and pharmacological intervention are conducted in single-cell culture systems, while the read-out of cellular engagement in disease and responsiveness to drugs in vivo is often based on overall tissue responses. As the majority of drugs under development aim to specifically interact with molecular targets in subsets of cells in complex tissues, this approach poses a major experimental discrepancy that prevents successful development of new therapeutics. In this review, we address the shortcomings of the use of artificial (single) cell systems and of whole tissue analyses in creating a better understanding of cell engagement in disease and of the true effects of drugs. We focus on microvascular endothelial cells that actively engage in a wide range of physiological and pathological processes. We propose a new strategy in which in vivo molecular control of cells is studied directly in the diseased endothelium instead of at a (far) distance from the site where drugs have to act, thereby accounting for tissue-controlled cell responses. The strategy uses laser microdissection-based enrichment of microvascular endothelium which, when combined with transcriptome and (phospho)proteome analyses, provides a factual view on their status in their complex microenvironment. Combining this with miniaturized sample handling using microfluidic devices enables handling the minute sample input that results from this strategy. The multidisciplinary approach proposed will enable compartmentalized analysis of cell behavior and drug effects in complex tissue to become widely implemented in daily biomedical research and drug development practice.

Organoazides are intermediates in the synthesis of imidometal complexes. Metalimido complexes have an important role in catalysis. Thus, the organoazide interaction with metals is an important issue. However, the isolation of organoazidometal complexes is difficult due to the easy loss of N-2. The present study describes the complexation of nickel by nitrobenzyl azides by means of electrospray ionization mass spectrometry (ESI-MS), which was used also as a probe for the characterization of isomers. Organoazidometal complexes were observed and isolated from solutions of NiCl2 and NiBr2 in methanol/water. A different solvent, ethanol/water was also used. The complexes detected were singly and doubly positively charged, with various stoichiometries. The most abundant species were [Ni(II)Az(3)](2+) for ortho- and para-isomers, and [Ni(II)Az(3)(H2O)](2+) for meta isomer, where Az stands for nitrobenzyl azides. The ortho isomer showed several single positively charged complexes integrating chloride as a ligand. The mass spectra of the three isomers allowed their differentiation based on different behaviour in the mass range m/z 296 m/z 312. The MS2 spectra of [Ni(II)Az(3)](2+) were investigated aiming to characterize the three isomers but this analysis was not absolutely conclusive about the coordination site(s). Density functional theory calculations provided possible structures for the [Ni(II)Az(3)](2+) cation with the different isomers and their coordination modes could be responsible for their fragmentation pathways. (C) 2013 Elsevier B.V. All rights reserved.

We show for the first time quantitative online measurements of five nitrated phenol (NP) compounds in ambient air (nitrophenol C6H5NO3, methylnitrophenol C7H7NO3, nitrocatechol C6H5NO4, methylnitrocatechol C7H7NO4, and dinitrophenol C6H4N2O5) measured with a micro-orifice volatilization impactor (MOVI) high-resolution chemical ionization mass spectrometer in Detling, United Kingdom during January-February, 2012. NPs absorb radiation in the near-ultraviolet (UV) range of the electromagnetic spectrum and thus are potential components of poorly characterized light-absorbing organic matter ("brown carbon") which can affect the climate and air quality. Total NP concentrations varied between less than 1 and 98 ng m(-3), with a mean value of 20 ng m(-3). We conclude that NPs measured in Detling have a significant contribution from biomass burning with an estimated emission factor of 0.2 ng (ppb CO)(-1). Particle light absorption measurements by a seven-wavelength aethalometer in the near-UV (370 nm) and literature values of molecular absorption cross sections are used to estimate the contribution of NP to wood burning brown carbon UV light absorption. We show that these five NPs are potentially important contributors to absorption at 370 nm measured by an aethalometer and account for 4 ± 2% of UV light absorption by brown carbon. They can thus affect atmospheric radiative transfer and photochemistry and with that climate and air quality.

The isoflavonoid profile of soybean was altered in different ways by stimulation of defense response upon germination. The combination of simultaneous germination and induction by Rhizopus oryzae increased the total isoflavonoid content of soybeans over 2-fold. Pterocarpans became the predominant isoflavonoids, up to 50% (w/w) of total isoflavonoids. To modulate both isoflavonoid content and composition further, the treatment was extended with wounding or light stimuli. The total isoflavonoid content could be increased over 3-fold compared to untreated beans by growing fungus-elicited soybean seedlings in light, whereas wounding was less effective. Interestingly, light altered the composition of prenylated pterocarpans by mediating the position of prenylation. The 2-prenylated pterocarpan level increased 2-fold, whereas that of 4-prenylated pterocarpan remained similar. Taken together, fungus was the most effective elicitor to alter the isoflavonoid content and composition of soybean seedlings, the impact of which can be further enhanced and mediated by additional stimuli, particularly light.

The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere., The growth rates of freshly formed aerosol particles influence what fraction of these can reach sizes large enough to affect cloud formation and climate. Here, the authors show that the nano-particle growth in a sulphuric acid containing system can be enhanced by the presence of ions or small acid-base clusters.

Porous aluminum oxide (PAO) is a ceramic formed by an anodization process of pure aluminum that enables the controllable assembly of exceptionally dense and regular nanopores in a planar membrane. As a consequence, PAO has a high porosity, nanopores with high aspect ratio, biocompatibility and the potential for high sensitivity imaging and diverse surface modifications. These properties have made this unusual material attractive to a disparate set of applications. This review examines how the structure and properties of PAO connect with its present and potential uses within research and biotechnology. The role of PAO is covered in areas including microbiology, mammalian cell culture, sensitive detection methods, microarrays and other molecular assays, and in creating new nanostructures with further uses within biology.

Observations of chemical constituents and meteorological quantities obtained during the two Arctic phases of the airborne campaign ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) are analyzed using an observationally constrained steady state box model. Measurements of OH and HO2 from the Penn State ATHOS instrument are compared to model predictions. Forty percent of OH measurements below 2 km are at the limit of detection during the spring phase (ARCTAS-A). While the median observed-to-calculated ratio is near one, both the scatter of observations and the model uncertainty for OH are at the magnitude of ambient values. During the summer phase (ARCTAS-B), model predictions of OH are biased low relative to observations and demonstrate a high sensitivity to the level of uncertainty in NO observations. Predictions of HO2 using observed CH2O and H2O2 as model constraints are up to a factor of two larger than observed. A temperature-dependent terminal loss rate of HO2 to aerosol recently proposed in the literature is shown to be insufficient to reconcile these differences. A comparison of ARCTAS-A to the high latitude springtime portion of the 2000 TOPSE campaign (Tropospheric Ozone Production about the Spring Equinox) shows similar meteorological and chemical environments with the exception of peroxides; observations of H2O2 during ARCTAS-A were 2.5 to 3 times larger than those during TOPSE. The cause of this difference in peroxides remains unresolved and has important implications for the Arctic HOx budget. Unconstrained model predictions for both phases indicate photochemistry alone is unable to simultaneously sustain observed levels of CH2O and H2O2; however when the model is constrained with observed CH2O, H2O2 predictions from a range of rainout parameterizations bracket its observations. A mechanism suitable to explain observed concentrations of CH2O is uncertain. Free tropospheric observations of acetaldehyde (CH3CHO) are 2–3 times larger than its predictions, though constraint of the model to those observations is sufficient to account for less than half of the deficit in predicted CH2O. The box model calculates gross O3 formation during spring to maximize from 1–4 km at 0.8 ppbv d−1, in agreement with estimates from TOPSE, and a gross production of 2–4 ppbv d−1 in the boundary layer and upper troposphere during summer. Use of the lower observed levels of HO2 in place of model predictions decreases the gross production by 25–50%. Net O3 production is near zero throughout the ARCTAS-A troposphere, and is 1–2 ppbv in the boundary layer and upper altitudes during ARCTAS-B.

Observations of a comprehensive suite of inorganic and organic trace gases, including non-methane hydrocarbons (NMHCs), halogenated organics and oxygenated volatile organic compounds (OVOCs), obtained from the NASA DC-8 over Canada during the ARCTAS aircraft campaign in July 2008 illustrate that convection is important for redistributing both long- and short-lived species throughout the troposphere. Convective outflow events were identified by the elevated mixing ratios of organic species in the upper troposphere relative to background conditions. Several dramatic events were observed in which isoprene and its oxidation products were detected at hundreds of pptv at altitudes higher than 8 km. Two events are studied in detail using detailed experimental data and the NASA Langley Research Center (LaRC) box model. One event had no lightning NOx (NO + NO2) associated with it and the other had substantial lightning NOx (LNOx > 1 ppbv). When convective storms transport isoprene from the boundary layer to the upper troposphere and no LNOx is present, OH is reduced due to scavenging by isoprene, which serves to slow the chemistry, resulting in longer lifetimes for species that react with OH. Ozone and PAN production is minimal in this case. In the case where isoprene is convected and LNOx is present, there is a large effect on the expected ensuing chemistry: isoprene exerts a dominant impact on HOx and nitrogen-containing species; the relative contribution from other species to HOx, such as peroxides, is insignificant. The isoprene reacts quickly, resulting in primary and secondary products, including formaldehyde and methyl glyoxal. The model predicts enhanced production of alkyl nitrates (ANs) and peroxyacyl nitrate compounds (PANs). PANs persist because of the cold temperatures of the upper troposphere resulting in a large change in the NOx mixing ratios which, in turn, has a large impact on the HOx chemistry. Ozone production is substantial during the first few hours following the convection to the UT, resulting in a net gain of approximately 10 ppbv compared to the modeled scenario in which LNOx is present but no isoprene is present aloft.

We use aircraft observations obtained during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) mission to examine the distributions and source attributions of O3 and NOy in the Arctic and sub-Arctic region. Using a number of marker tracers, we distinguish various air masses from the background troposphere and examine their contributions to NOx, O3, and O3 production in the Arctic troposphere. The background Arctic troposphere has a mean O3 of ~60 ppbv and NOx of ~25 pptv throughout spring and summer with CO decreasing from ~145 ppbv in spring to ~100 ppbv in summer. These observed mixing ratios are not notably different from the values measured during the 1988 ABLE-3A and the 2002 TOPSE field campaigns despite the significant changes in emissions and stratospheric ozone layer in the past two decades that influence Arctic tropospheric composition. Air masses associated with stratosphere-troposphere exchange are present throughout the mid and upper troposphere during spring and summer. These air masses, with mean O3 concentrations of 140–160 ppbv, are significant direct sources of O3 in the Arctic troposphere. In addition, air of stratospheric origin displays net O3 formation in the Arctic due to its sustainable, high NOx (75 pptv in spring and 110 pptv in summer) and NOy (~800 pptv in spring and ~1100 pptv in summer). The air masses influenced by the stratosphere sampled during ARCTAS-B also show conversion of HNO3 to PAN. This active production of PAN is the result of increased degradation of ethane in the stratosphere-troposphere mixed air mass to form CH3CHO, followed by subsequent formation of PAN under high NOx conditions. These findings imply that an adequate representation of stratospheric NOy input, in addition to stratospheric O3 influx, is essential to accurately simulate tropospheric Arctic O3, NOx and PAN in chemistry transport models. Plumes influenced by recent anthropogenic and biomass burning emissions observed during ARCTAS show highly elevated levels of hydrocarbons and NOy (mostly in the form of NOx and PAN), but do not contain O3 higher than that in the Arctic tropospheric background except some aged biomass burning plumes sampled during spring. Convection and/or lightning influences are negligible sources of O3 in the Arctic troposphere but can have significant impacts in the upper troposphere in the continental sub-Arctic during summer.

Many pathophysiological conditions are associated with increased gastrointestinal permeability, reflecting an elevated risk of endotoxaemia, inflammation, and sepsis. Permeability tests are increasingly used in clinical practice to obtain information on gastrointestinal functioning, but tests are often restricted to the small intestine, and require large oral sugar doses. Therefore, a novel multi-sugar assay was developed, allowing assessment of whole gut permeability changes in urinary and plasma samples collected at regular intervals from 10 healthy volunteers at baseline and after intake of monosaccharides (rhamnose and erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection conditions were optimized. After centrifugation, chromatographic separation was achieved on an IOA-1000 column set at 30 degrees C. Column effluent was mixed with ammonia for sugar-ammonium adduct formation. The lower limit of detection was 0.05mumol/L for disaccharides and 0.1mumol/L for monosaccharides. Linearity for each probe was between 1 and 1000mumol/L (R(2): 0.9987-0.9999). Coefficients of variation were

An in vitro study was conducted to investigate effects of tannins on extent and rate of gas and CH4 production using an automated pressure evaluation system (APES). In this study three condensed tannins (CT; quebracho, grape seed, green tea tannins) and four hydrolysable tannins (HT; tara, valonea, myrabolan, chestnut tannins) were evaluated with lucerne as a control substrate. CT and HT were characterised by matrix assisted laser desorption ionisation–time of flight mass spectrometry (MALDI–TOF MS). Tannins were added to the substrate at an effective concentration of 100 g/kg, either with or without polyethylene glycol (PEG 6000), and incubated for 72 h in pooled buffered rumen liquid from four lactating dairy cows. After inoculation, fermentation bottles were immediately connected to the APES to measure total cumulative gas production (GP). During the incubation, 11 gas samples were collected from each bottle at 0, 1, 4, 7, 11, 15, 23, 30, 46, 52 and 72 h of incubation and analysed for CH4. A modified Michaelis–Menten model was fitted to the CH4 concentration patterns, and model estimates were used to calculate total cumulative CH4 production ( G P C H 4 ). GP and G P C H 4 curves were fitted using a modified monophasic Michaelis–Menten model. Addition of quebracho reduced (P=0.002) GP, whilst the other tannins did not affect GP. Addition of PEG increased GP for quebracho (P=0.003), valonea (P=0.058) and grape seed tannins (P=0.071), suggesting that these tannins either inhibited, or tended to inhibit, fermentation. Addition of quebracho and grape seed tannins reduced (P≤0.012) the maximum rate of gas production, indicating that microbial activity was affected. Quebracho, valonea, myrabolan and grape seed decreased (P≤0.003) G P C H 4 and the maximum rate (0.001≤P≤0.102) of CH4 production. Addition of chestnut, green tea and tara tannins did not affect total gas nor CH4 production. Vvalonea and myrabolan tannins have the most promise at reducing CH4 production as they had only a minor impact on gas production. This article is part of the special issue entitled: Greenhouse Gases in Animal Agriculture – Finding a Balance between Food and Emissions, Guest Edited by T.A. McAllister, Section Guest Editors; K.A. Beauchemin, X. Hao, S. McGinn and Editor for Animal Feed Science and Technology, P.H. Robinson.

We determine enhancement ratios for NOx, PAN, and other NOy species from boreal biomass burning using aircraft data obtained during the ARCTAS-B campaign and examine the impact of these emissions on tropospheric ozone in the Arctic. We find an initial emission factor for NOx of 1.06 g NO per kg dry matter (DM) burned, much lower than previous observations of boreal plumes, and also one third the value recommended for extratropical fires. Our analysis provides the first observational confirmation of rapid PAN formation in a boreal smoke plume, with 40% of the initial NOx emissions being converted to PAN in the first few hours after emission. We find little clear evidence for ozone formation in the boreal smoke plumes during ARCTAS-B in either aircraft or satellite observations, or in model simulations. Only a third of the smoke plumes observed by the NASA DC8 showed a correlation between ozone and CO, and ozone was depleted in the plumes as often as it was enhanced. Special observations from the Tropospheric Emission Spectrometer (TES) also show little evidence for enhanced ozone in boreal smoke plumes between 15 June and 15 July 2008. Of the 22 plumes observed by TES, only 4 showed ozone increasing within the smoke plumes, and even in those cases it was unclear that the increase was caused by fire emissions. Using the GEOS-Chem atmospheric chemistry model, we show that boreal fires during ARCTAS-B had little impact on the median ozone profile measured over Canada, and had little impact on ozone within the smoke plumes observed by TES.

The solid compounds [La(3)(chel)(Hchel)(3)(H(2)O)(8)]center dot H(2)O (1) and [La(Hchel)(H(2)O)(6)](2)[La(2)(Hchel)(4)(H(2)O)(4)]center dot 10H(2)O (2) (H(3)chel = 4-hydroxypyridine-2,6-dicarboxylic acid or chelidamic acid) were isolated from aqueous solutions upon mixing La(3+) cations and chelidamic acid at various pHs (pH 5-10). Compound I is a two-dimensional (213) coordination polymer consisting of La(Hchel)and La(Hchel)(2) units connected bycoordination bonds. Compound 2 is an ion-pair complex made Lip of alternating layers of La(Hchel)(+) and La(2)(Hchel)(4)(2-) ionic units linked between them by lattice water Molecules. The comparison of the two structures showed that the 2D coordination polymer, 1, is formed by a dehydration-condensation reaction between the La(Hchel)(+) and La(2)(Hchel)(4)(2-) units. The relative positions of these units in the crystal lattice suggest that the assembly of 1 takes place by a dehydration-condensation reaction between oligomeric layers of opposite charge and not by reaction between individual ions of opposite charge. Crystal Growth & Design

The mitochondrial phospholipid cardiolipin plays an important role in cellular metabolism as exemplified by its involvement in mitochondrial energy production and apoptosis. Following its biosynthesis, cardiolipin is actively remodeled to achieve its final acyl composition. An important cardiolipin remodeling enzyme is tafazzin, of which several mRNA splice variants exist. Mutations in the tafazzin gene cause the X-linked recessive disorder Barth syndrome. In addition to providing an overview of the current knowledge in literature about tafazzin, we present novel experimental data and use this to discuss the functional role of the different tafazzin variants in cardiolipin metabolism in relation to Barth syndrome. We developed and performed specific quantitative PCR analyses of different tafazzin mRNA splice variants in 16 human tissues and correlated this with the tissue cardiolipin profile. In BTHS fibroblasts we showed that mutations in the tafazzin gene affected both the level and distribution of tafazzin mRNA variants. Transient expression of selected human tafazzin variants in BTHS fibroblasts showed for the first time in a human cell system that tafazzin lacking exon5 indeed functions in cardiolipin remodeling. (C) 2009 Elsevier B.V. All rights reserved.

The objective of this study was to determine to what extent the attenuation or loss of andic soil properties caused by land use change ¿ from forest (FOR, average C content 118.2 ± 23.7 g kg¿1) to agricultural land (AGR, average C content 55.7 ± 16.7 g kg¿1) use ¿ is reflected in soil organic matter (SOM) at the molecular level. For this, NaOH-extractable SOM of A horizons from 17 soils developed on amphibolitic parent material in NW Spain was studied by pyrolysis gas chromatography spectrometry (Py-GC/MS). We also included two buried andic A horizons (PAL, 2200 cal yr BP in age) on the same parent material, as a reference for the molecular composition of SOM from soils without recent litter additions. Organic matter of PAL soils had a composition largely different from that of superficial soils (FOR and AGR), with an important relative contribution of microbial polysaccharides and N-compounds, and an absence of compounds that characterize fresh plant litter (e.g. lignins). In the superficial soils, the relative contribution of lignin-derived compounds was greater in AGR than in FOR soils. Differences were also observed in the relative contribution of aliphatic compounds, FOR soils being enriched in this type of components compared with AGR soils. The results indicated that land use change from FOR to AGR, which was accompanied by a decrease in total SOM, resulted in an enrichment in primary SOM. The smaller relative abundance of primary SOM derivatives in andic FOR soils indicates that these compounds were quickly degraded in Andisols

The intrinsically disordered and amyloidogenic protein α-synuclein (AS) has been linked to several neurodegenerative states, including Parkinsons disease. Here, nanoelectrospray-ionization mass spectrometry (nano-ESI-MS), ion mobility (IM), and native top-down electron transfer dissociation (ETD) techniques are employed to study AS interaction with small molecules known to modulate its aggregation, such as epigallocatechin-3-gallate (EGCG) and dopamine (DA). The complexes formed by the two ligands under identical conditions reveal peculiar differences. While EGCG engages AS in compact conformations, DA preferentially binds to the protein in partially extended conformations. The two ligands also have different effects on AS structure as assessed by IM, with EGCG leading to protein compaction and DA to its extension. Native top-down ETD on the proteinligand complexes shows how the different observed modes of binding of the two ligands could be related to their known opposite effects on AS aggregation. The results also show that the protein can bind either ligand in the absence of any covalent modifications, such as oxidation.

Article, Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90 % relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid–dimethylamine, and sulfuric acid–organics derived from α-pinene oxidation. The hygroscopicity parameter κ decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5.1 × 106 molecules cm−3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured κ of 15 nm particles was 0.31 ± 0.01: close to the value reported for dimethylaminium sulfate (DMAS) (κDMAS ∼ 0.28). Furthermore, the difference in κ between sulfuric acid and sulfuric acid–imethylamine experiments increased with increasing particle size. The κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes., published version, peerReviewed

The Maillard reaction product 3-deoxyglucosone (3DG) was quantified in wines, by high-performance liquid chromatography-mass spectrometry analysis after derivatization with ortho-phenylenediamine. Both sweet red Port wines and dry white wines were analysed during natural and forced aging. In natural aging, and for dry white wines, 3DG is negatively correlated to age (r=0.939), while for sweet red Port wines, 3DG is positively correlated to age (r=0.782). The same tendency was observed during a wine forced aging protocol. For a dry white wine, with higher levels of alpha-amino acids, 3DG is consumed (k(consumption) 0.077-0.098 day(-1)) along the time protocol, while for a sweet red Port wine, with lower levels of alpha-amino acids, an accumulation of 3DG is observed with time (k(formation) 0.041-0.060 day(-1)). These results suggest that 3DG content can be used as an aging marker, as it has discriminated dry white and sweet red Port wines from different ages and cultivars. Analysis of wine-model solutions allowed verifying that the fructose content has a higher effect on 3DG formation than glucose, as well as that an increase on amino acids content does not lead to an increase of 3DG yields. (C) 2016 Elsevier Inc. All rights reserved.

International audience; Agricultural activities involve the use of crop preservation such as "trench-type" silo, which can sometimes be contaminated by fungi. To investigate the exposure of livestock and farm workers to fungal spores and mycotoxins, a multimycotoxin analysis method has been developed. Six mycotoxins (aflatoxin B-1, citrinin, deoxynivalenol, gliotoxin, ochratoxin A, and zearalenone) were quantified by high-performance liquid chromatography coupled to mass spectrometry after solid-phase extraction. An experimental study of fungal species and mycotoxins was conducted in corn silage (Normandy, France) during 9 months of monitoring. The results indicated the recurrence of around 20 different species, with some of them being potentially toxigenic fungi such as Aspergillus fumigatus, Aspergillus parasiticus, Fusarium verticillioides, and Monascus ruber, and the detection of aflatoxin B1 (4-34 ppb), citrinin (4-25 ppb), zearalenone (23-41 ppb), and deoxynivalenol (100-213 ppb). This suggested a possible chronic exposure to low levels of mycotoxins.

International audience; The NADPH-dependent dimeric flavoenzyme 4-hydroxyacetophenone monooxygenase (HAPMO) catalyzes Baeyer-Villiger oxidations of a wide range of ketones, thereby generating esters or lactones. In the current work, we probed HAPMO-coenzyme complexes present during the enzyme catalytic cycle with the aim to gain mechanistic insight. Moreover, we investigated the structural role of the nicotinamide coenzyme. For these studies, we used (i) wild type HAPMO, (ii) the R339A variant, which is active but has a low affinity toward NADPH, and (iii) the R440A variant, which is inactive but has a high affinity toward NADPH. Electrospray ionization mass spectrometry was used as the primary tool to directly observe noncovalent protein-coenzyme complexes in real time. These analyzes showed for the first time that the nicotinamide coenzyme remains bound to HAPMO during the entire catalytic cycle of the NADPH oxidase reaction. This may also have implications for other homologous Baeyer-Villiger monooxygenases. Together with the observations that NADP(+) only weakly interacts with oxidized enzyme and that HAPMO is mainly in the reduced form during catalysis, we concluded that NADP(+) interacts tightly with the reduced form of HAPMO. We also demonstrated that the association with the coenzyme is crucial for enzyme stability. The interaction with the coenzyme analog 3-aminopyridine adenine dinucleotide phosphate (AADP(+)) strongly enhanced the thermal stability of wild type HAPMO. This coenzyme-induced stabilization may also be important for related enzymes.

Toxicogenomics can facilitate the identification and characterization of toxicity, as illustrated in this review. Toxicogenomics, the application of the functional genomics technologies (transcriptomics, proteomics and metabolomics) in toxicology enables the study of adverse effects of xenobiotic substances in relation to structure and activity of the genome. The advantages and limitations of the different technologies are evaluated, and the prospects for integration of the technologies into a systems biology or systems toxicology approach are discussed. Applications of toxicogenomics in various laboratories around the world show that the crucial steps and sequence of events at the molecular level can be studied to provide detailed insights into mechanisms of toxic action. Toxicogenomics allowed for more sensitive and earlier detection of adverse effects in (animal) toxicity studies. Furthermore, the effects of exposure to mixtures could be studied in more detail. This review argues that in the (near) future, human health risk assessment will truly benefit from toxicogenomics (systems toxicology).