Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides

peer-reviewedXanthine oxidase (XO) and dipeptidyl peptidase IV (DPP-IV) inhibition by amino acids and dipeptides was studied. Trp and Trp-containing dipeptides (Arg-Trp, Trp-Val, Val-Trp, Lys-Trp and Ile-Trp) inhibited XO. Three amino acids (Met, Leu and Trp) and eight dipeptides (Phe-Leu, Trp-Val, His-Leu, Glu-Lys, Ala-Leu, Val-Ala, Ser-Leu and Gly-Leu) inhibited DPP-IV. Trp and Trp-Val were multifunctional inhibitors of XO and DPP-IV. Lineweaver and Burk analysis showed that Trp was a non-competitive inhibitor of XO and a competitive inhibitor of DPP-IV. Molecular docking with Autodock Vina was used to better understand the interaction of the peptides with the active site of the enzyme. Because of the non-competitive inhibition observed, docking of Trp-Val to the secondary binding sites of XO and DPP-IV is required. Trp-Val was predicted to be intestinally neutral (between 25% and 75% peptide remaining after 60 min simulated intestinal digestion). These results are of significance for the reduction of reactive oxygen species (ROS) and the increase of the half-life of incretins by food-derived peptides. (C) 2013 Elsevier Ltd. All rights reserved.ACCEPTEDpeer-reviewe

A Multi-wavelength View of the TeV Blazar Markarian 421: Correlated Variability, Flaring, and Spectral Evolution

We report results from a multi-wavelength monitoring campaign on Mrk 421 over the period of 2003-2004. The source was observed simultaneously at TeV and X-ray energies, with supporting observations frequently carried out at optical and radio wavelengths. The large amount of simultaneous data has allowed us to examine the variability of Mrk 421 in detail. The variabilities are generally correlated between the X-ray and gamma-ray bands, although the correlation appears to be fairly loose. The light curves show the presence of flares with varying amplitudes on a wide range of timescales both at X-ray and TeV energies. Of particular interest is the presence of TeV flares that have no coincident counterparts at longer wavelengths, because the phenomenon seems difficult to understand in the context of the proposed emission models for TeV blazars. We have also found that the TeV flux reached its peak days before the X-ray flux during a giant flare in 2004. Such a difference in the development of the flare presents a further challenge to the emission models. Mrk 421 varied much less at optical and radio wavelengths. Surprisingly, the normalized variability amplitude in optical seems to be comparable to that in radio, perhaps suggesting the presence of different populations of emitting electrons in the jet. The spectral energy distribution (SED) of Mrk 421 is seen to vary with flux, with the two characteristic peaks moving toward higher energies at higher fluxes. We have failed to fit the measured SEDs with a one-zone SSC model; introducing additional zones greatly improves the fits. We have derived constraints on the physical properties of the X-ray/gamma-ray flaring regions from the observed variability (and SED) of the source. The implications of the results are discussed. (Abridged)Comment: 32 pages, 12 figures, to appear in Ap

The TeV spectrum of H1426+428

The BL Lac object H1426+428 was recently detected as a high energy gamma-ray source by the VERITAS collaboration (Horan et al. 2002). We have reanalyzed the 2001 portion of the data used in the detection in order to examine the spectrum of H1426+428 above 250 GeV. We find that the time-averaged spectrum agrees with a power law of the shape dF/dE = 10^(-7.31 +- 0.15(stat) +- 0.16(syst)) x E^(-3.50 +- 0.35(stat) +- 0.05(syst)) m^(-2)s^(-1)TeV^(-1) The statistical evidence from our data for emission above 2.5 TeV is 2.6 sigma. With 95% c.l., the integral flux of H1426+428 above 2.5 TeV is larger than 3% of the corresponding flux from the Crab Nebula. The spectrum is consistent with the (non-contemporaneous) measurement by Aharonian et al. (2002) both in shape and in normalization. Below 800 GeV, the data clearly favours a spectrum steeper than that of any other TeV Blazar observed so far indicating a difference in the processes involved either at the source or in the intervening space.Comment: LaTeX, 8 pages, 4 figures, accepted for publication in Ap

Search for High Energy Gamma Rays from an X-ray Selected Blazar Sample

Our understanding of blazars has been greatly increased in recent years by extensive multi-wavelength observations, particularly in the radio, X-ray and gamma-ray regions. Over the past decade the Whipple 10m telescope has contributed to this with the detection of 5 BL Lacertae objects at very high gamma-ray energies. The combination of multi-wavelength data has shown that blazars follow a well-defined sequence in terms of their broadband spectral properties. Together with providing constraints on emission models, this information has yielded a means by which potential sources of TeV emission may be identified and predictions made as to their possible gamma-ray flux. We have used the Whipple telescope to search for TeV gamma-ray emission from eight objects selected from a list of such candidates. No evidence has been found for VHE emission from the objects in our sample, and upper limits have been derived for the mean gamma-ray flux above 390GeV. These flux upper limits are compared with the model predictions and the implications of our results for future observations are discussed.Comment: 15 pages, 2 figures, Accepted for publication in Ap

A Search for TeV Gamma-Ray Emission from High-Peaked Flat Spectrum Radio Quasars Using the Whipple Air-Cherenkov Telescope

Blazars have traditionally been separated into two broad categories based upon their optical emission characteristics; BL Lacs, with faint or no emission lines, and flat spectrum radio quasars (FSRQs) with prominent, broad emission lines. The spectral energy distribution of FSRQs has generally been thought of as being more akin to the low-peaked BL Lacs, which exhibit a peak in the infrared region of the spectrum, as opposed to high-peaked BL Lacs (HBLs), which exhibit a peak in UV/X-ray region of the spectrum. All blazars currently confirmed as sources of TeV emission are HBLs. Recent surveys have found several FSRQs exhibiting spectral properties similar to HBLs, particularly the synchrotron peak frequency. These objects are potential sources of TeV emission according to several models of blazar jet emission and blazar evolution. Measurements of TeV flux or upper limits could impact existing theories explaining the links between different blazar types and could have a significant impact on our understanding of the nature of objects that are capable of TeV emission. In particular, the presence (or absence) of TeV emission from FSRQs could confirm (or cast doubt upon) recent evolutionary models that expect intermediate objects in a transitionary state between FSRQ and BL Lac. The Whipple 10 meter imaging air-Cherenkov gamma-ray telescope is well suited for TeV gamma-ray observations. Using the Whipple telescope, we have taken data on a small selection of nearby(z<0.1 in most cases), high-peaked FSRQs. Although one of the objects, B2 0321+33, showed marginal evidence of flaring, no significant emission was detected. The implications of this paucity of emission and the derived upper limits are discussed.Comment: accepted for publication in Astrophysical Journa

A Very High Energy Gamma-Ray Spectrum of 1ES 2344+514

The BL Lacertae (BL Lac) object 1ES 2344+514 (1ES 2344), at a redshift of 0.044, was discovered as a source of very high energy (VHE) gamma rays by the Whipple Collaboration in 1995 \citep{2344Catanese98}. This detection was recently confirmed by the HEGRA Collaboration \citep{2344Hegra03}. As is typical for high-frequency peaked blazars, the VHE gamma-ray emission is highly variable. On the night of 20 December, 1995, a gamma-ray flare of 5.3-sigma significance was detected, the brightest outburst from this object to-date. The emission region is compatible with a point source. The spectrum between 0.8 TeV and 12.6 TeV can be described by a power law $\frac{ ^3 N}{ E A t}=(5.1\pm1.0_{st}\pm1.2_{sy})\times10^{-7} (E/ \mathrm{TeV})^{-2.54 \pm0.17_{st}\pm0.07_{sy}} \mathrm{\frac{1}{TeV m^2 s}}$. Comparing the spectral index with that of the other five confirmed TeV blazars, the spectrum of 1ES 2344 is similar to 1ES 1959+650, located at almost the same distance. The spectrum of 1ES 2344 is steeper than the brightest flare spectra of Markarian 421 (Mrk~421) and Markarian 501 (Mrk~501), both located at a distance about 2/3 that of 1ES 2344, and harder than the spectra of PKS 2155-304 and H~1426+428, which are located almost three times as far. This trend is consistent with attenuation caused by the infrared extragalactic background radiation.Comment: 27 pages, 11 figures, accepted by Ap

Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape

Citation: Leys, B. A., Commerford, J. L., & McLauchlan, K. K. (2017). Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape. Plos One, 12(4), 15. doi:10.1371/journal.pone.0176445Fire is a key Earth system process, with 80% of annual fire activity taking place in grassland areas. However, past fire regimes in grassland systems have been difficult to quantify due to challenges in interpreting the charcoal signal in depositional environments. To improve reconstructions of grassland fire regimes, it is essential to assess two key traits: (1) charcoal count, and (2) charcoal shape. In this study, we quantified the number of charcoal pieces in 51 sediment samples of ponds in the Great Plains and tested its relevance as a proxy for the fire regime by examining 13 potential factors influencing charcoal count, including various fire regime components (e.g. the fire frequency, the area burned, and the fire season), vegetation cover and pollen assemblages, and climate variables. We also quantified the width to length (W: L) ratio of charcoal particles, to assess its utility as a proxy of fuel types in grassland environments by direct comparison with vegetation cover and pollen assemblages. Our first conclusion is that charcoal particles produced by grassland fires are smaller than those produced by forest fires. Thus, a mesh size of 120 mu m as used in forested environments is too large for grassland ecosystems. We recommend counting all charcoal particles over 60 mu m in grasslands and mixed grass-forest environments to increase the number of samples with useful data. Second, a W: L ratio of 0.5 or smaller appears to be an indicator for fuel types, when vegetation surrounding the site is before composed of at least 40% grassland vegetation. Third, the area burned within 1060m of the depositional environments explained both the count and the area of charcoal particles. Therefore, changes in charcoal count or charcoal area through time indicate a change in area burned. The fire regimes of grassland systems, including both human and climatic influences on fire behavior, can be characterized by long-term charcoal records

A Graph Algorithmic Approach to Separate Direct from Indirect Neural Interactions

Network graphs have become a popular tool to represent complex systems composed of many interacting subunits; especially in neuroscience, network graphs are increasingly used to represent and analyze functional interactions between neural sources. Interactions are often reconstructed using pairwise bivariate analyses, overlooking their multivariate nature: it is neglected that investigating the effect of one source on a target necessitates to take all other sources as potential nuisance variables into account; also combinations of sources may act jointly on a given target. Bivariate analyses produce networks that may contain spurious interactions, which reduce the interpretability of the network and its graph metrics. A truly multivariate reconstruction, however, is computationally intractable due to combinatorial explosion in the number of potential interactions. Thus, we have to resort to approximative methods to handle the intractability of multivariate interaction reconstruction, and thereby enable the use of networks in neuroscience. Here, we suggest such an approximative approach in the form of an algorithm that extends fast bivariate interaction reconstruction by identifying potentially spurious interactions post-hoc: the algorithm flags potentially spurious edges, which may then be pruned from the network. This produces a statistically conservative network approximation that is guaranteed to contain non-spurious interactions only. We describe the algorithm and present a reference implementation to test its performance. We discuss the algorithm in relation to other approximative multivariate methods and highlight suitable application scenarios. Our approach is a tractable and data-efficient way of reconstructing approximative networks of multivariate interactions. It is preferable if available data are limited or if fully multivariate approaches are computationally infeasible.Comment: 24 pages, 8 figures, published in PLOS On

Spectrum of very high energy gamma-rays from the blazar 1ES 1959+650 during flaring activity in 2002

The blazar 1ES 1959+650 was observed in a flaring state with the Whipple 10 m Imaging Atmospheric Cerenkov Telescope in 2002 May. A spectral analysis has been carried out on the data from that time period, and the resulting very high energy gamma-ray spectrum (E greater than or equal to 316 GeV) can be well fitted by a power law of differential spectral index alpha = 2.78 +/- 0.12(stat) +/- 0.21(sys). On 2002 June 4, the source flared dramatically in the gamma-ray range without any coincident increase in the X-ray emission, providing the first unambiguous example of an orphan\u27\u27 gamma-ray flare from a blazar. The gamma-ray spectrum for these data can also be described by a simple power-law fit with alpha = 2.82 +/- 0.15(stat) +/- 0.30(sys). There is no compelling evidence for spectral variability or for any cutoff to the spectrum