Using exomarkers to assess mitochondrial reactive species in vivo

Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scope of review: One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Major conclusions and general significance: Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Abbreviations: EPR, electron paramagnetic resonance; GFP, green fluorescent protein; 4-HNE, 4-hydroxynonenal; MitoB, 3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide; MitoP, (3-hydroxybenzyl)triphenylphosphonium bromide; ROS, reactive oxygen species; SOD, superoxide dismutase; TPMP, methyltriphenylphosphonium; TPP, triphenylphosphonium catio

Longitudinal Proton Polarization in the Cooler

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Selective Uncoupling of Individual Mitochondria within a Cell Using a Mitochondria-Targeted Photoactivated Protonophore

Depolarization of an individual mitochondrion or small clusters of mitochondria within cells has been achieved using a photoactivatable probe. The probe is targeted to the matrix of the mitochondrion by an alkyltriphenylphosphonium lipophilic cation and releases the protonophore 2,4-dinitrophenol locally in predetermined regions in response to directed irradiation with UV light via a local photolysis system. This also provides a proof of principle for the general temporally and spatially controlled release of bioactive molecules, pharmacophores, or toxins to mitochondria with tissue, cell, or mitochondrion specificity

Form Factors in the radiative pion decay

We perform an analysis of the form factors that rule the structure-dependent amplitude in the radiative pion decay. The resonance contributions to pion -> e nu_e gamma decays are computed through the proper construction of the vector and axial-vector form factors by setting the QCD driven asymptotic properties of the three-point Green functions VVP and VAP, and by demanding the smoothing of the form factors at high transfer of momentum. A comparison between theoretical and experimental determinations of the form factors is also carried out. We also consider and evaluate the role played by a non-standard tensor form factor. We conclude that, at present and due to the hadronic incertitudes, the search for New Physics in this process is not feasible.Comment: 14 pages, no figures. Typos corrected. Accepted for publication in The European Physical Journal

Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor

We present the discovery of an optical transient (OT) in Messier 51, designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed luminosity of $M_r=-13$ (${\nu}L_{\nu}=9\times10^6~L_{\odot}$), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of $\approx400$ km s$^{-1}$, Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called "SN impostors" and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a $4.5~\mu$m luminosity of $M_{[4.5]}\approx-12.2$ and a $[3.6]-[4.5]$ color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of $E(B-V)\approx0.7$ mag and higher intrinsic luminosity of $M_r\approx-14.9$ (${\nu}L_{\nu}=5.3\times10^7~L_{\odot}$) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51 OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ

Detection of interstellar oxidaniumyl: abundant H2O+ towards the star-forming regions DR21, Sgr B2, and NGC6334

We identify a prominent absorption feature at 1115 GHz, detected in first HIFI spectra towards high-mass star-forming regions, and interpret its astrophysical origin. The characteristic hyperfine pattern of the H2O+ ground-state rotational transition, and the lack of other known low-energy transitions in this frequency range, identifies the feature as H2O+ absorption against the dust continuum background and allows us to derive the velocity profile of the absorbing gas. By comparing this velocity profile with velocity profiles of other tracers in the DR21 star-forming region, we constrain the frequency of the transition and the conditions for its formation. In DR21, the velocity distribution of H2O+ matches that of the [CII] line at 158\mu\m and of OH cm-wave absorption, both stemming from the hot and dense clump surfaces facing the HII-region and dynamically affected by the blister outflow. Diffuse foreground gas dominates the absorption towards Sgr B2. The integrated intensity of the absorption line allows us to derive lower limits to the H2O+ column density of 7.2e12 cm^-2 in NGC 6334, 2.3e13 cm^-2 in DR21, and 1.1e15 cm^-2 in Sgr B2.Comment: Accepted for publication in A&

MicroRNA Expression in Abdominal and Gluteal Adipose Tissue Is Associated with mRNA Expression Levels and Partly Genetically Driven

To understand how miRNAs contribute to the molecular phenotype of adipose tissues and related traits, we performed global miRNA expression profiling in subcutaneous abdominal and gluteal adipose tissue of 70 human subjects and characterised which miRNAs were differentially expressed between these tissues. We found that 12% of the miRNAs were significantly differentially expressed between abdominal and gluteal adipose tissue (FDR adjusted p<0.05) in the primary study, of which 59 replicated in a follow-up study of 40 additional subjects. Further, 14 miRNAs were found to be associated with metabolic syndrome case-control status in abdominal tissue and three of these replicated (primary study: FDR adjusted p<0.05, replication: p<0.05 and directionally consistent effect). Genome-wide genotyping was performed in the 70 subjects to enable miRNA expression quantitative trait loci (eQTL) analysis. Candidate miRNA eQTLs were followed-up in the additional 40 subjects and six significant, independent cis-located miRNA eQTLs (primary study: p<0.001; replication: p<0.05 and directionally consistent effect) were identified. Finally, global mRNA expression profiling was performed in both tissues to enable association analysis between miRNA and target mRNA expression levels. We find 22% miRNAs in abdominal and 9% miRNAs in gluteal adipose tissue with expression levels significantly associated with the expression of corresponding target mRNAs (FDR adjusted p<0.05). Taken together, our results indicate a clear difference in the miRNA molecular phenotypic profile of abdominal and gluteal adipose tissue, that the expressions of some miRNAs are influenced by cis-located genetic variants and that miRNAs are associated with expression levels of their predicted mRNA targets

Evidence for Irradiation Triggered Nonuniform Defect Distribution In Multiharmonic Magnetic Susceptibility of Neutron Irradiated YBa2Cu3O7-x

Multiharmonic ac-magnetic susceptibility \ch11,\chi2,chi3, of neutron irradiated Li-doped YBa2Cu3O7-x has revealed a nonmonotonic dependence of all harmonics on the neutron fluence. The irradiation has a strongly depressive influence on the intergrain connection suggesting an increase of the effective thickness of the intergranular Josephson junction at aneutron fluence of 0.98x10$^{17}$ cm$_{-2}$. Less damaged are the intragrain properties. A spectacular enhancement of the superconducting intragranular properties reflected in the characteristics of all harmonics was observed at highest fluence \Phi = 9.98x10$^{17}$ cm$_{-2}$. We assume that this effect results from the development of a space inhomogeneous distribution with alternating defectless and defect rich regions.Comment: 24 pages, 9 figures, accepted to J. Supercon

Experimental search for super and hyper heavy nuclei at cyclotron Institute Texas A&M University

The question "How heavy can an atomic nucleus be?" is a fundamental problem in nuclear physics. The possible existence of island(s) of stable super-heavy nuclei has been an inspiring problem in heavy ion physics for almost four decades. This paper is focused on the experimental search of Super/Hyper Heavy Elements (SHE/HHE) conducted at the Cyclotron Institute, Texas A&M University. A novel experimental idea and experimental set up introduced for this research will be presented