Synthesis, X-ray Structures, Electronic Properties, and O\u3csub\u3e2\u3c/sub\u3e/NO Reactivities of Thiol Dioxygenase Active-Site Models

Mononuclear non-heme iron complexes that serve as structural and functional mimics of the thiol dioxygenases (TDOs), cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO), have been prepared and characterized with crystallographic, spectroscopic, kinetic, and computational methods. The high-spin Fe(II) complexes feature the facially coordinating tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP) ligand that replicates the three histidine (3His) triad of the TDO active sites. Further coordination with bidentate l-cysteine ethyl ester (CysOEt) or cysteamine (CysAm) anions yielded five-coordinate (5C) complexes that resemble the substrate-bound forms of CDO and ADO, respectively. Detailed electronic-structure descriptions of the [Fe(Ph2TIP)(LS,N)]BPh4 complexes, where LS,N = CysOEt (1) or CysAm (2), were generated through a combination of spectroscopic techniques [electronic absorption, magnetic circular dichroism (MCD)] and density functional theory (DFT). Complexes 1 and 2 decompose in the presence of O2 to yield the corresponding sulfinic acid (RSO2H) products, thereby emulating the reactivity of the TDO enzymes and related complexes. Rate constants and activation parameters for the dioxygenation reactions were measured and interpreted with the aid of DFT calculations for O2-bound intermediates. Treatment of the TDO models with nitric oxide (NO)—a well-established surrogate of O2—led to a mixture of high-spin and low-spin {FeNO}7 species at low temperature (−70 °C), as indicated by electron paramagnetic resonance (EPR) spectroscopy. At room temperature, these Fe/NO adducts convert to a common species with EPR and infrared (IR) features typical of cationic dinitrosyl iron complexes (DNICs). To complement these results, parallel spectroscopic, computational, and O2/NO reactivity studies were carried out using previously reported TDO models that feature an anionic hydrotris(3-phenyl-5-methyl-pyrazolyl)borate (Ph,MeTp–) ligand. Though the O2 reactivities of the Ph2TIP- and Ph,MeTp-based complexes are quite similar, the supporting ligand perturbs the energies of Fe 3d-based molecular orbitals and modulates Fe–S bond covalency, suggesting possible rationales for the presence of neutral 3His coordination in CDO and ADO

Reconciling optical and radio observations of the binary millisecond pulsar PSR J1640+2224

Previous optical and radio observations of the binary millisecond pulsar PSR J1640+2224 have come to inconsistent conclusions about the identity of its companion, with some observations suggesting the companion is a low-mass helium-core (He-core) white dwarf (WD), while others indicate it is most likely a high-mass carbon-oxygen (CO) WD. Binary evolution models predict PSR J1640+2224 most likely formed in a low-mass X-ray binary (LMXB) based on the pulsar's short spin period and long-period, low-eccentricity orbit, in which case its companion should be a He-core WD with mass about $0.35 - 0.39 \, M_\odot$, depending on metallicity. If it is instead a CO WD, that would suggest the system has an unusual formation history. In this paper we present the first astrometric parallax measurement for this system from observations made with the Very Long Baseline Array (VLBA), from which we determine the distance to be $1520^{+170}_{-150}\,\mathrm{pc}$. We use this distance and a reanalysis of archival optical observations originally taken in 1995 with the Wide Field Planetary Camera 2 (WFPC2) on the Hubble Space Telescope (HST) in order to measure the WD's mass. We also incorporate improvements in calibration, extinction model, and WD cooling models. We find that the existing observations are not sufficient to tightly constrain the companion mass, but we conclude the WD mass is $>0.4\,M_\odot$ with $>90\%$ confidence. The limiting factor in our analysis is the low signal-to-noise ratio of the original HST observations.Comment: 6 pages, 5 figure

Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells.

Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34(+) hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds

What is an endangered species?: judgments about acceptable risk

Judgments about acceptable risk in the context of policy may be influenced by law makers, policy makers, experts and the general public. While significant effort has been made to understand public attitudes on acceptable risk of environmental pollution, little is known about such attitudes in the context of species\u27 endangerment. We present survey results on these attitudes in the context of United States\u27 legal-political apparatus intended to mitigate species endangerment. The results suggest that the general public exhibit lower tolerance for risk than policy makers and experts. Results also suggest that attitudes about acceptable risk for species endangerment are importantly influenced by one\u27s knowledge about the environment and social identity. That result is consistent with notions that risk judgments are a synthesis of facts and values and that knowledge is associated with one\u27s social identity. We explain the implications of these findings for understanding species endangerment across the planet

Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection

Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fc gamma receptor-bearing cells. While IgM and IgG are the most commonly studied DENV-reactive antibody isotypes, our group and others have described the induction of DENV-specific serum IgA responses during dengue. We hypothesized that monomeric IgA would be able to neutralize DENV without the possibility of ADE. To test this, we synthesized IgG and IgA versions of two different DENV-reactive monoclonal antibodies. We demonstrate that isotype-switching does not affect the antigen binding and neutralization properties of the two mAbs. We show that DENV-reactive IgG, but not IgA, mediates ADE in Fc gamma receptor-positive K562 cells. Furthermore, we show that IgA potently antagonizes the ADE activity of IgG. These results suggest that levels of DENV-reactive IgA induced by DENV infection might regulate the overall IgG mediated ADE activity of DENV-immune plasma in vivo, and may serve as a predictor of disease risk

Anderson localisation in steady states of microcavity polaritons

We present an experimental signature of the Anderson localisation of microcavity polaritons, and provide a systematic study of the dependence on disorder strength. We reveal a controllable degree of localisation, as characterised by the inverse-participation ratio, by tuning the positional disorder of arrays of interacting mesas. This constitutes the realisation of disorder-induced localisation in a driven-dissipative system. In addition to being an ideal candidate for investigating localisation in this regime, microcavity polaritons hold promise for low-power, ultra-small devices and their localisation could be used as a resource in quantum memory and quantum information processing.Comment: 7 pages, 3 figure

Search for high-frequency periodicities in time-tagged event data from gamma ray bursts and soft gamma repeaters

We analyze the Time-Tagged Event (TTE) data from observations of gamma ray bursts (GRBs) and soft gamma repeaters (SGRs) by the Burst and Transient Source Experiment (BATSE). These data provide the best available time resolution for GRBs and SGRs. We have performed an extensive search for weak periodic signals in the frequency range 400 Hz to 2500 Hz using the burst records for 2203 GRBs and 152 SGR flares. The study employs the Rayleigh power as a test statistic to evaluate the evidence for periodic emissions. We find no evidence of periodic emissions from these events at these frequencies. In all but a very few cases the maximum power values obtained are consistent with what would be expected by chance from a non-periodic signal. In those few instances where there is marginal evidence for periodicity there are problems with the data that cast doubt on the reality of the signal. For classical GRBs, the largest Rayleigh power occurs in bursts whose TTE data appear to be corrupted. For SGRs, our largest Rayleigh power, with a significance of 1%, occurs in one record for SGR 1900+14 (at 2497 Hz), and in no other outbursts associated with this source; we thus consider it unlikely to represent detection of a real periodicity. From simulations, we deduce that the Rayleigh test would have detected significant oscillations with relative amplitude ~10% about half the time. Thus, we conclude that high frequency oscillations, if present, must have small relative amplitudes.Comment: 22 pages, 7 figures, submitted to Ap

Toward TeV Conformality

We study the chiral condensate $$ for an SU(3) gauge theory with $N_f$ massless Dirac fermions in the fundamental representation when $N_f$ is increased from 2 to 6. For $N_f=2$, our lattice simulations of $<\bar{\psi} \psi >/F^3$, where $F$ is the Nambu-Goldstone-boson decay constant, agree with the measured QCD value. For $N_f = 6$, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as $N_f$ increases further, toward the critical value for transition from confinement to infrared conformality.Comment: 4 pages, 4 figures. v2: revised version for PR