731 research outputs found
Genome of Diaporthe sp. provides insights into the potential inter-phylum transfer of a fungal sesquiterpenoid biosynthetic pathway.
Made available in DSpace on 2017-08-22T09:28:35Z (GMT). No. of bitstreams: 1
Genome.pdf: 1649894 bytes, checksum: 15ed2d80128563978cbd38ead7301c5c (MD5)
Previous issue date: 2017-02-0
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
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
Measurement of H<sub>2</sub>O<sub>2</sub> within living drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix
Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due to the difficulty of measuring mitochondrial H<sub>2</sub>O<sub>2</sub> in vivo. Here we report a ratiometric mass spectrometry probe approach to assess mitochondrial matrix H<sub>2</sub>O<sub>2</sub> levels in vivo. The probe, MitoB, comprises a triphenylphosphonium (TPP) cation driving its accumulation within mitochondria, conjugated to an arylboronic acid that reacts with H<sub>2</sub>O<sub>2</sub> to form a phenol, MitoP. Quantifying the MitoP/MitoB ratio by liquid chromatography-tandem mass spectrometry enabled measurement of a weighted average of mitochondrial H<sub>2</sub>O<sub>2</sub> that predominantly reports on thoracic muscle mitochondria within living flies. There was an increase in mitochondrial H<sub>2</sub>O<sub>2</sub> with age in flies, which was not coordinately altered by interventions that modulated life span. Our findings provide approaches to investigate mitochondrial ROS in vivo and suggest that while an increase in overall mitochondrial H<sub>2</sub>O<sub>2</sub> correlates with aging, it may not be causative
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
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 (), 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
km s, 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 m luminosity of
and a 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 mag and higher
intrinsic luminosity of
() 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
- …