Environmental and Genotypic Influences on Isoquinoline Alkaloid Content in Sanguinaria canadensis

In a common garden, we investigated genetic and environmental influences on alkaloid production using Sanguinaria canadensis as a model. Nutrient and shade regimes were applied to replicated clones over one growing season, and induction of alkaloid production in bloodroot was tested on a whole-plant basis using jasmonic acid as an elicitor. Alkaloid concentrations increased with decreasing light intensity and fertilizer levels. Induction was not achieved by foliar application of jasmonic acid. Genetic influences represented by clone effects may be indicated by variation in alkaloid concentration by clone, but this experimental design did not allow us to distinguish genetic from pre-experiment environmental influences on the rhizomes.     

A Structural Rationale for N-Methylbicuculline Acting as a Promiscuous Competitive Antagonist of Inhibitory Pentameric Ligand-Gated Ion Channels

Bicuculline, a valued chemical tool in neurosciences research, is a competitive antagonist of specific GABA_A receptors and affects other pentameric ligand-gated ion channels including the glycine, nicotinic acetylcholine and 5-hydroxytryptamine type 3 receptors. We used a fluorescence-quenching assay and isothermal titration calorimetry to record low-micromolar dissociation constants for N-methylbicuculline interacting with acetylcholine-binding protein and an engineered version called glycine-binding protein (GBP), which provides a surrogate for the heteromeric interface of the extracellular domain of the glycine receptor (GlyR). The 2.4 Å resolution crystal structure of the GBP:N-methylbicuculline complex, sequence and structural alignments reveal similarities and differences between GlyR and the GABA_A receptor–bicuculline interactions. N-methylbicuculline displays a similar conformation in different structures, but adopts distinct orientations enforced by interactions and steric blocks with key residues and plasticity in the binding sites. These features explain the promiscuous activity of bicuculline against the principal inhibitory pentameric ligand-gated ion channels in the CNS.     

Enhanced gas migration through permeable bubble networks within consolidated soft sediments

Many consolidated sediments experience in situ gas generation from methanogenesis, corrosion, or radiolysis reactions and can retain bubbles for long periods. Particular interest is motivated by the retention and acute release of flammable hydrogen from nuclear legacy waste sludge. X‐ray computed tomography was employed to observe 0.07–10 mm bubble populations within 30–1112 Pa yield strength Mg(OH)₂ sediments. High rates of partial coalescence were observed among sub‐millimeter microvoids, forming extensive bubble networks which spanned the 32 mm field of view. Lattice Boltzmann and Monte Carlo modeling demonstrated these networks to be highly pervious to gas, with effective diffusivities for hydrogen of 3.7–12.5 × 10^?5 m² s^?1. Continuous vessel‐spanning bubble networks, dynamic connectivity between ganglia of coalesced bubbles, Haines jumps, and composite diffusion through the gas and aqueous phase can account for enhanced gas migration over length‐scales of several meters, thus enabling chronic gas release from low‐intermediate strength sediments ( kPa) too strong for buoyant bubble ebullition and too weak for vertical channel formation. © 2018 The Authors. AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers. AIChE J, 64: 4131–4147, 2018     

Determination of the Fe2+/Fe3+ Ratio in Nuclear Waste Glasses

The Fe²⁺/Fe³⁺ ratios of 47 simulated nuclear waste glass samples with ratios varying from 0.01 (oxidized) to 1.6 (reduced) were determined by wet-chemical and Mössbauer spectral analyses. The wet-chemical method involved the spectrophotometric determination of Fe²⁺ and total iron using remote spectroscopy with fiber optic chemical sensing. Interferences from other species present in these glasses were examined and alternative analytical techniques were investigated. Results of wet-chemical and Mössbauer spectral analysis were comparable; however, the wet-chemical method is probably preferable for the analysis of highly radioactive glasses until such glasses have been shown to have satisfactory Mössbauer spectra.     

Synthesis and characterization of cytidine derivatives that inhibit the kinase IspE of the non-mevalonate pathway for isoprenoid biosynthesis

The enzymes of the non-mevalonate pathway for isoprenoid biosynthesis are attractive targets for the development of novel drugs against malaria and tuberculosis. This pathway is used exclusively by the corresponding pathogens, but not by humans. A series of water-soluble, cytidine-based inhibitors that were originally designed for the fourth enzyme in the pathway, IspD, were shown to inhibit the subsequent enzyme, the kinase IspE (from Escherichia coli). The binding mode of the inhibitors was verified by co-crystal structure analysis, using Aquifex aeolicus IspE. The crystal structures represent the first reported example of a co-crystal structure of IspE with a synthetic ligand and confirmed that ligand binding affinity originates mainly from the interactions of the nucleobase moiety in the cytidine binding pocket of the enzyme. In contrast, the appended benzimidazole moieties of the ligands adopt various orientations in the active site and establish only poor intermolecular contacts with the protein. Defined binding sites for sulfate ions and glycerol molecules, components in the crystallization buffer, near the well-conserved ATP-binding Gly-rich loop of IspE were observed. The crystal structures of A. aeolicus IspE nicely complement the one from E. coli IspE for use in structure-based design, namely by providing invaluable structural information for the design of inhibitors targeting IspE from Mycobacterium tuberculosis and Plasmodium falciparum. Similar to the enzymes from these pathogens, A. aeolicus IspE directs the OH group of a tyrosine residue into a pocket in the active site. In the E. coli enzyme, on the other hand, this pocket is lined by phenylalanine and has a more pronounced hydrophobic character.     

In situ observation of dynamic elastic modulus in polypyrrole actuators

Polypyrrole is a leading conducting polymer actuator, but the factors that influence its performance when actuated under load in devices (such as the polymer stiffness) are not yet fully understood. To this end, we have probed the dynamic elastic modulus of polypyrrole in situ during actuation in a variety of electrolytes. As part of this study, we demonstrate that the electroactive response in dilute 1-butyl-3-methylimidazolium hexafluorophosphate can be changed from cation- to anion-dominated by adjusting the applied potential waveform. We observe that when conservative electrochemical conditions are applied in order to avoid dual ion movement or significant transfer of neutral solvent, the stiffness is determined by level of counterion swelling. The elastic modulus decreases during the net influx of ions into the bulk polymer and increases as these ions are expelled, regardless of whether the electroactive response is cation- or anion-dominated or whether there is a neutral solvent present in the electrolyte. This effect is quite significant, and we have observed up to a 3× increase in elastic modulus upon actuation in neat 1-butyl-3-methylimidazolium hexafluorophosphate.     

Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8–12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.     

Relative effects of cultivar, heat-treatment and sucrose content on the sensory properties of blackcurrant juice

The effects of processing treatments (heat, sucrose addition) on the sensory quality of blackcurrant juices prepared from two genetically diverse cultivars (Ben Lomond and Ben Alder) were examined using sensory profiling. Sucrose level had the largest effect on the sensory profile, with heating and cultivar having smaller but still significant effects. Some interaction between sucrose level and heating of the juices was observed in the sensory profile. The results indicate that selection of preferred genotypes remains an important breeding objective in blackcurrant improvement programmes, since the sensory attributes associated with genotype persist, despite processing effects, in the extracted juice.     

An appraisal of the Great Lakes advanced hydrologic prediction system

Great Lakes water level forecasts are used to inform decisions ranging from personal choices of recreational activities to corporate evaluations of alternative cargo transport options. For effective decision-making it is important that these model-based forecasts include an accurate expression of the forecast uncertainty, as well as information regarding the model forecasting skill. We provide an assessment of water level forecasts from 1997 through 2009 that were made using the National Oceanic and Atmospheric Administration (NOAA) Great Lakes Environmental Research Laboratory (GLERL) Advanced Hydrologic Prediction System (AHPS). A visual comparison between observed and forecast water levels suggests that AHPS generally captures seasonal and inter-annual patterns. A more quantitative assessment based on the percentage of observations within 90% prediction intervals, however, indicates that AHPS generally underestimates the observed variability of Great Lakes water levels. This assessment provides a benchmark for forecast performance against which alternative model structures (including future evolutions of AHPS) can be tested, and a basis to identify and prioritize the implementation of those alternatives. Including a calibrated model error term into the AHPS framework, to accommodate the underestimated variability, is a priority for short-term development and research, and represents one step toward more accurately quantifying forecast uncertainty. Our results also underscore the importance of storing historical forecasts and the data from which they were derived to serve as a basis for assessing model performance and prioritizing future model improvements.     

Concentrations of polybrominated diphenyl ethers in air and soil on a rural-urban transect across a major UK conurbation

Polybrominated diphenyl ethers (PBDEs) were measured in air (using PUF disk passive samplers) and soil samples taken at approximately monthly intervals over 1 year at 10 locations on a transect across the West Midlands of the UK. Concentrations in air are consistent with those detected elsewhere in Europe and the Great Lakes basin. Concentrations in soil fall within the range reported for rural woodland and grassland soils in the UK and Norway. In both air and soil, concentrations clearly decrease with increasing distance from the city center, supporting the existence of an urban "pulse", indicating the West Midlands conurbation to be a source of PBDEs to the wider environment. Examination of seasonal trends revealed no evidence of a "spring pulse" in concentrations in air, with no summer peak in concentrations in air observed for 70% of sites. The PBDE congener pattern in air differs from that in soil, with ratios of congeners 47:99 higher in air than in soil. It is hypothesized that PBDEs volatilize from treated products indoors, before ventilating outdoors, where congener 99 undergoes preferential atmospheric deposition and accumulation in soil.