Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype

Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18–30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: ERCC5 Asp1104His (rs17655); XPC Lys939Gln (rs2228001); ERCC2 Lys751Gnl (rs13181); XPC PAT (an 83 bp poly A/T insertion–deletion polymorphism in the XPC gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene–gene interactions were observed between XPC Lys939Gln and ERCC5 Asp1104His and XPC Lys939Gln and ERCC2 Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the ERCC2 Lys751Gnl single nucleotide polymorphism

Crystal polymorphism of methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-d-glucopyranouronate

The polymorphism of the glycoside donor methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-d-glucopyranouronate (1) has been investigated. Two polymorphic forms (labelled Forms I and II) have been elucidated and fully characterised by DSC, PXRD and single crystal analysis, both crystallizing in the space group P21. Form I was obtained by crystallization from a wide range of solvents, while Form II was obtained only from ethyl acetate or isopropanol on certain occasions. Unit cell dimensions for Form I are a 14.0292(12), b 8.9641(8), c 16.8580(14) Å, β 94.285(2)°, and for Form II a 11.266(3), b 6.8889(17), c 13.921(4) Å, β 101.161(6)°. Z’ is 2 for Form I and 1 for Form II. Form I displays two moderate intermolecular hydrogen bonds in the unit cell whereas Form II shows no moderate hydrogen-bonding motifs. All three molecules in the two polymorphs differ significantly in their conformations, especially with respect to the methyl carboxylate and trichloroacetimidoyl group

Effect of Daily Fluctuations from Flaming Gorge Dam on Ice Processes in the Green River

This report provides results and conclusions of a detailed investigation of ice processes in the main channel of the reach of the Green River between the downstream end of Split Mountain (River Mile [RM1] 320) and the Ouray, Utah Bridge (R.M248). The objective of the study was to examine the influence of daily fluctuations in water releases from Flaming Gorge Damon river ice processes in this reach, which serves as an overwintering area for endangered Colorado pikeminnow and razorback sucker. The objective of the study was met through examination of historical records of winter water and air temperatures, flow measurements, and ice observations; through measurements of differences in ice conditions under steady and fluctuating flow regimes; and through calibration and use of an ice process model to compare hydraulic and ice conditions expected under steady and fluctuating flow regimes

Investigation of paediatric PKU breath malodour, comparing glycomacropeptide with phenylalanine free L-amino acid supplements

In clinical practice, caregivers of children with phenylketonuria (PKU) report that their children have breath malodour. This might be linked to the regular consumption of low phenylalanine (Phe)/Phe-free protein substitutes (PS), which are an essential component of a low-Phe diet. Oral malodour can negatively affect interpersonal communication, lead to bullying, low self-esteem and social isolation. In this longitudinal cross-over study, exhaled volatile organic compounds (VOCs) were measured using gas chromatography - ion mobility spectrometry (GC-IMS). 40 children (20 PKU, 20 controls) were recruited. Subjects with PKU took either L-Amino Acid (L-AA) or Casein Glycomacropeptide (CGMP-AA) exclusively for 1 week, in a randomised order. On the 7th day, 7 exhaled breath samples were collected over a 10-hr period. Subjects then transferred to the other PS for a week and on day 7, provided 7 further breath samples. All subjects had a standardised menu using low-Phe food alternatives and all food intake was measured and recorded. In the PKU group, the aim was to collect samples 30-min after consuming PS. In 3 subjects, breath was collected 5-min post-PS consumption. Fasted L-AA and CGMP-AA breath samples contained a similar number of VOC peaks (10-12) as controls. Longitudinal breath testing results demonstrate that there was no significant difference in the number of exhaled VOCs, comparing L-AA or CGMP-AA with controls, or between PS (12-18 VOC peaks). Breath analysed immediately after consumption of PS (n=3) showed an immediate increase in the number of VOC peaks (25-30), but these were no longer detectable at 30-min post-consumption. This suggests PS have a transient effect on exhaled breath. Measurements taken 30-min after consuming L-AA or CGMP-AA were not significantly different to controls. This indicates that timing food and drinks with PS consumption may be a potential solution for carers to reduce or eliminate unpleasant PS-related breath odours. [Abstract copyright: © 2019 IOP Publishing Ltd.

To move or to evolve: contrasting patterns of intercontinental connectivity and climatic niche evolution in “Terebinthaceae” (Anacardiaceae and Burseraceae)

Many angiosperm families are distributed pantropically, yet for any given continent little is known about which lineages are ancient residents or recent arrivals. Here we use a comprehensive sampling of the pantropical sister pair Anacardiaceae and Burseraceae to assess the relative importance of continental vicariance, long-distance dispersal and niche-conservatism in generating its distinctive pattern of diversity over time. Each family has approximately the same number of species and identical stem age, yet Anacardiaceae display a broader range of fruit morphologies and dispersal strategies and include species that can withstand freezing temperatures, whereas Burseraceae do not. We found that nuclear and chloroplast data yielded a highly supported phylogenetic reconstruction that supports current taxonomic concepts and time-calibrated biogeographic reconstructions that are broadly congruent with the fossil record. We conclude that the most recent common ancestor of these families was widespread and likely distributed in the Northern Hemisphere during the Cretaceous and that vicariance between Eastern and Western Hemispheres coincided with the initial divergence of the families. The tempo of diversification of the families is strikingly different. Anacardiaceae steadily accumulated lineages starting in the Late Cretaceous–Paleocene while the majority of Burseraceae diversification occurred in the Miocene. Multiple dispersal- and vicariance-based intercontinental colonization events are inferred for both families throughout the past 100 million years. However, Anacardiaceae have shifted climatic niches frequently during this time, while Burseraceae have experienced very few shifts between dry and wet climates and only in the tropics. Thus, we conclude that both Anacardiaceae and Burseraceae move easily but that Anacardiaceae have adapted more often, either due to more varied selective pressures or greater intrinsic lability

Model- and calibration-independent test of cosmic acceleration

We present a calibration-independent test of the accelerated expansion of the universe using supernova type Ia data. The test is also model-independent in the sense that no assumptions about the content of the universe or about the parameterization of the deceleration parameter are made and that it does not assume any dynamical equations of motion. Yet, the test assumes the universe and the distribution of supernovae to be statistically homogeneous and isotropic. A significant reduction of systematic effects, as compared to our previous, calibration-dependent test, is achieved. Accelerated expansion is detected at significant level (4.3 sigma in the 2007 Gold sample, 7.2 sigma in the 2008 Union sample) if the universe is spatially flat. This result depends, however, crucially on supernovae with a redshift smaller than 0.1, for which the assumption of statistical isotropy and homogeneity is less well established.Comment: 13 pages, 2 figures, major change

Atom probe tomography of a Cu-doped TiNiSn thermoelectric material : nanoscale structure and optimization of analysis conditions

Funding: The Oxford Atom Probe facility is funded by EPSRC (EP/M022803/1) and the Glasgow plasma focused ion beam system was funded by EPSRC grant EP/P001483/1. Thermoelectric materials were developed under joint EPSRC grants EP/N017218/1 and EP/N01717X/1.Cu-doping and crystallographic site occupations within the half-Heusler (HH) TiNiSn, a promising thermoelectric material, have been examined by atom probe tomography. In particular, this investigation aims to better understand the influence of atom probe analysis conditions on the measured chemical composition. Under a voltage-pulsing mode, atomic planes are clearly resolved and suggest an arrangement of elements in-line with the expected HH (F-43m space group) crystal structure. The Cu dopant is also distributed uniformly throughout the bulk material. For operation under laser-pulsed modes, the returned composition is highly dependent on the selected laser energy, with high energies resulting in the measurement of excessively high absolute Ti counts at the expense of Sn and in particular Ni. High laser energies also appear to be correlated with the detection of a high fraction of partial hits, indicating nonideal evaporation behavior. The possible mechanisms for these trends are discussed, along with suggestions for optimal analysis conditions for these and similar thermoelectric materials.PostprintPeer reviewe