Identification of 2-Piperidone as a Biomarker of CYP2E1 Activity Through Metabolomic Phenotyping

Cytochrome P450 2E1 (CYP2E1) is a key enzyme in the metabolic activation of many low molecular weight toxicants and also an important contributor to oxidative stress. A noninvasive method to monitor CYP2E1 activity in vivo would be of great value for studying the role of CYP2E1 in chemical-induced toxicities and stress-related diseases. In this study, a mass spectrometry-based metabolomic approach was used to identify a metabolite biomarker of CYP2E1 through comparing the urine metabolomes of wild-type (WT), Cyp2e1-null, and CYP2E1-humanized mice. Metabolomic analysis with multivariate models of urine metabolites revealed a clear separation of Cyp2e1-null mice from WT and CYP2E1-humanized mice in the multivariate models of urine metabolomes. Subsequently, 2-piperidone was identified as a urinary metabolite that inversely correlated to the CYP2E1 activity in the three mouse lines. Backcrossing of WT and Cyp2e1-null mice, together with targeted analysis of 2-piperidone in mouse serum, confirmed the genotype dependency of 2-piperidone. The accumulation of 2-piperidone in the Cyp2e1-null mice was mainly caused by the changes in the biosynthesis and degradation of 2-piperidone because compared with the WT mice, the conversion of cadaverine to 2-piperidone was higher, whereas the metabolism of 2-piperidone to 6-hydroxy-2-piperidone was lower in the Cyp2e1-null mice. Overall, untargeted metabolomic analysis identified a correlation between 2-piperidone concentrations in urine and the expression and activity of CYP2E1, thus providing a noninvasive metabolite biomarker that can be potentially used in to monitor CYP2E1 activit

A Unified Description of Cuprate and Iron Arsenide Superconductors

We propose a unified description of cuprate and iron-based superconductivity. Consistency with magnetic structure inferred from neutron scattering implies significant constraints on the symmetry of the pairing gap for the iron-based superconductors. We find that this unification requires the orbital pairing formfactors for the iron arsenides to differ fundamentally from those for cuprates at the microscopic level.Comment: 12 pages, 10 figures, 2 table

MYOD-1 in normal colonic mucosa : role as a putative biomarker?

Background DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Results We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development. Conclusions Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer

Efficient glueball simulations on anisotropic lattices

Monte Carlo results for the low-lying glueball spectrum using an improved, anisotropic action are presented. Ten simulations at lattice spacings ranging from 0.2 to 0.4 fm and two different anisotropies have been performed in order demonstrate the advantages of using coarse, anisotropic lattices to calculate glueball masses. Our determinations of the tensor (2++) and pseudovector (1+-) glueball masses are more accurate than previous Wilson action calculations.Comment: 43 pages, LaTeX (with revtex). 13 postscript figures. Submitted to Phys. Rev.

Pion-nucleus elastic scattering on 12C, 40Ca, 90Zr, and 208Pb at 400 and 500 MeV

Pion-nucleus elastic scattering at energies above the Delta(1232) resonance is studied using both pi+ and pi- beams on 12C, 40Ca, 90Zr, and 208Pb. The present data provide an opportunity to study the interaction of pions with nuclei at energies where second-order corrections to impulse approximation calculations should be small. The results are compared with other data sets at similar energies, and with four different first-order impulse approximation calculations. Significant disagreement exists between the calculations and the data from this experiment

Release 2 data products from the Ozone Mapping and Profiler Suite (OMPS) Limb Profiler

The OMPS Limb Profiler (LP) was launched on board the NASA Suomi National Polar-orbiting Partnership (SNPP) satellite in October 2011. OMPS-LP is a limb-scattering hyperspectral sensor that provides ozone profiling capability at 1.5 km vertical resolution from cloud top to 60 km altitude. The use of three parallel slits allows global coverage in approximately four days. We have recently completed a full reprocessing of all LP data products, designated as Release 2, that improves the accuracy and quality of these products. Level 1 gridded radiance (L1G) changes include intra-orbit and seasonal correction of variations in wavelength registration, revised static and intra-orbit tangent height adjustments, and simplified pixel selection from multiple images. Ozone profile retrieval changes include removal of the explicit aerosol correction, exclusion of channels contaminated by stratospheric OH emission, a revised instrument noise characterization, improved synthetic solar spectrum, improved pressure and temperature ancillary data, and a revised ozone climatology. Release 2 data products also include aerosol extinction coefficient profiles derived with the prelaunch retrieval algorithm. Our evaluation of OMPS LP Release 2 data quality is good. Zonal average ozone profile comparisons with Aura MLS data typically show good agreement, within 5-10% over the altitude range 20-50 km between 60 deg S and 60 deg N. The aerosol profiles agree well with concurrent satellite measurements such as CALIPSO and OSIRIS, and clearly detect exceptional events such as volcanic eruptions and the Chelyabinsk bolide in February 2013

“I can do everything but see!” – How People with Vision Impairments Negotiate their Abilities in Social Contexts

This research takes an orientation to visual impairment (VI) that does not regard it as fixed or determined alone in or through the body. Instead, we consider (dis)ability as produced through interactions with the environment and configured by the people and technology within it. Specifically, we explore how abilities become negotiated through video ethnography with six VI athletes and spectators during the Rio 2016 Paralympics. We use generated in-depth examples to identify how technology can be a meaningful part of ability negotiations, emphasizing how these embed into the social interactions and lives of people with VI. In contrast to treating technology as a solution to a ‘sensory deficit’, we understand it to support the triangulation process of sense-making through provision of appropriate additional information. Further, we suggest that technology should not try and replace human assistance, but instead enable people with VI to better identify and interact with other people in-situ