Decreased Anti-Inflammatory Responses to Vitamin D in Neonatal Neutrophils

Neutrophil activity is prolonged in newborns, suggesting decreased exposure and/or responses to immunosuppressive modulators, such as 1,25-hydroxyvitamin D3 (1,25-vit D3). We hypothesized that 1,25-vit D3 suppresses neutrophil activation and that this response is impaired in newborns. Consistent with this, 1,25-vit D3 decreased LPS-induced expression of macrophage inflammatory protein-1β and VEGF in adult, but not neonatal, neutrophils. Expression of vitamin D receptor (VDR) and 25-hydroxyvitamin D3-1α-hydroxylase was reduced in neonatal, relative to adult neutrophils. Moreover, 1,25-vit D3 induced VDR gene expression in activated adult, but not neonatal, neutrophils. 1,25-vit D3 also suppressed expression of cyclooxygenase-2 and induced expression of 5-lipoxygenase in LPS-exposed adult neutrophils, while neonatal cells were not affected. 1,25-vit D3 had no effect on respiratory burst in either adult or neonatal cells. Anti-inflammatory activity of vitamin D is impaired in neonatal neutrophils, and this may be due to decreased expression of VDR and 1α-hydroxylase. Insensitivity to 1,25-vit D3 may contribute to chronic inflammation in neonates

Reduced Expression of Inflammatory Genes in Deceased Donor Kidneys Undergoing Pulsatile Pump Preservation

Background The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys. Methodology/Principal Findings 99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24–62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/−509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/−485 minutes) (P Conclusions/Significance Inflammation was the most important up-regulated pattern associated with pre-implantation biopsies undergoing CSP even when the PPP group has a larger number of ECD kidneys. No significant difference was observed in delayed graft function incidence and graft function post-transplantation. These findings support the use of PPP in ECD donor kidneys

Synthesis, Characterization, and Computational Study of Three-Coordinate SNS Copper(I) Complexes Based on Bis-Thione Ligand Precursors

A series of tridentate pincer ligands, each possessing two sulfur and one nitrogen donor (SNS), based on bis-imidazolyl or bis-triazolyl salts were metallated with CuCl2 to give new tridentate SNS pincer copper(I) complexes [(SNS)Cu]+. These orange complexes exhibit a three-coordinate pseudo-trigonal-planar geometry in copper. During the formation of these copper(I) complexes, disproportionation is observed as the copper(II) salt precursor is converted into the Cu(I) [(SNS)Cu]+ cation and the [CuCl4]2– counteranion. The [(SNS)Cu]+ complexes were characterized with single crystal X-ray diffraction, electrospray mass spectrometry, EPR spectroscopy, attenuated total reflectance infrared spectroscopy, UV–Vis spectroscopy, cyclic voltammetry, and elemental analysis. The EPR spectra are consistent with anisotropic Cu(II) signals with four hyperfine splittings in the lower-field region (g||) and g values consistent with the presence of the tetrachlorocuprate. Various electronic transitions are apparent in the UV–Vis spectra of the complexes and originate in the copper-containing cations and anions. Density functional calculations support the nature of the SNS binding, allowing assignment of a number of features present in the UV–Vis and IR spectra and cyclic voltammograms of these complexes

Syntheses and characterization of three-and five-coordinate copper(II) complexes based on SNS pincer ligand precursors

A series of tridentate pincer ligands, each possessing two sulfur- and one nitrogen-donor functionalities (SNS), based on a bis-imidazolyl precursor were metallated with CuCl2 to give new tridentate SNS pincer copper(II) complexes [(SNS)CuCl2]. These purple complexes exhibit a five-coordinate pseudo-square pyramidal geometry at the copper center. The [(SNS)CuCl2] complexes were characterized with single crystal X-ray diffraction, electrospray mass spectrometry, EPR spectroscopy, attenuated total reflectance infrared spectroscopy, UV–Vis spectroscopy, cyclic voltammetry, and elemental analysis. The EPR spectra are consistent with typical anisotropic Cu(II) signals with four hyperfine splittings in the lower-field region (g||). Various electronic transitions are apparent in the UV–Vis spectra of the complexes and originate from d-to-d transitions or various charge transfer transitions. We preformed computational studies to understand the influence that structural constraints internal to our tridentate SNS ligand precursors have on the oxidation state of the resulting bound copper complex. We have determined that a d9 copper(II) metal center is better situated than a d10 copper(I) center to bind our tridentate SNS ligand set when it does not contain an internal CH2 group. Without this methylene linker, the SNS ligand forces the N and S atoms into a T-shaped arrangement about the metal center

Gamma-ray Observations Under Bright Moonlight with VERITAS

Imaging atmospheric Cherenkov telescopes (IACTs) are equipped with sensitive photomultiplier tube (PMT) cameras. Exposure to high levels of background illumination degrades the efficiency of and potentially destroys these photo-detectors over time, so IACTs cannot be operated in the same configuration in the presence of bright moonlight as under dark skies. Since September 2012, observations have been carried out with the VERITAS IACTs under bright moonlight (defined as about three times the night-sky-background (NSB) of a dark extragalactic field, typically occurring when Moon illumination > 35%) in two observing modes, firstly by reducing the voltage applied to the PMTs and, secondly, with the addition of ultra-violet (UV) bandpass filters to the cameras. This has allowed observations at up to about 30 times previous NSB levels (around 80% Moon illumination), resulting in 30% more observing time between the two modes over the course of a year. These additional observations have already allowed for the detection of a flare from the 1ES 1727+502 and for an observing program targeting a measurement of the cosmic-ray positron fraction. We provide details of these new observing modes and their performance relative to the standard VERITAS observations

Evidence for proton acceleration up to TeV energies based on VERITAS and Fermi-LAT observations of the Cas A SNR

We present a study of $\gamma$-ray emission from the core-collapse supernova remnant Cas~A in the energy range from 0.1GeV to 10TeV. We used 65 hours of VERITAS data to cover 200 GeV - 10 TeV, and 10.8 years of \textit{Fermi}-LAT data to cover 0.1-500 GeV. The spectral analysis of \textit{Fermi}-LAT data shows a significant spectral curvature around $1.3 \pm 0.4_{stat}$ GeV that is consistent with the expected spectrum from pion decay. Above this energy, the joint spectrum from \textit{Fermi}-LAT and VERITAS deviates significantly from a simple power-law, and is best described by a power-law with spectral index of $2.17\pm 0.02_{stat}$ with a cut-off energy of $2.3 \pm 0.5_{stat}$ TeV. These results, along with radio, X-ray and $\gamma$-ray data, are interpreted in the context of leptonic and hadronic models. Assuming a one-zone model, we exclude a purely leptonic scenario and conclude that proton acceleration up to at least 6 TeV is required to explain the observed $\gamma$-ray spectrum. From modeling of the entire multi-wavelength spectrum, a minimum magnetic field inside the remnant of $B_{\mathrm{min}}\approx150\,\mathrm{\mu G}$ is deduced.Comment: 33 pages, 9 Figures, 6 Table

Dark Matter Constraints from a Joint Analysis of Dwarf Spheroidal Galaxy Observations with VERITAS

We present constraints on the annihilation cross section of WIMP dark matter based on the joint statistical analysis of four dwarf galaxies with VERITAS. These results are derived from an optimized photon weighting statistical technique that improves on standard imaging atmospheric Cherenkov telescope (IACT) analyses by utilizing the spectral and spatial properties of individual photon events. We report on the results of $\sim$230 hours of observations of five dwarf galaxies and the joint statistical analysis of four of the dwarf galaxies. We find no evidence of gamma-ray emission from any individual dwarf nor in the joint analysis. The derived upper limit on the dark matter annihilation cross section from the joint analysis is $1.35\times 10^{-23} {\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the bottom quark ($b\bar{b}$) final state, $2.85\times 10^{-24}{\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the tau lepton ($\tau^{+}\tau^{-}$) final state and $1.32\times 10^{-25}{\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the gauge boson ($\gamma\gamma$) final state.Comment: 14 pages, 9 figures, published in PRD, Ascii tables containing annihilation cross sections limits are available for download as ancillary files with readme.txt file description of limit