4,950 research outputs found
The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis.
Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency.This work was supported by an EMBL long-term postdoctoral fellowship to B.Y.C., Sir Henry Wellcome Fellowships to B.Y.C. and N.I., a Wellcome Trust PhD scholarship to J.D.J., a Wellcome Trust Fellowship to A.E.F. (088789), and UK Biotechnology and Biological Sciences Research Council grants to I.B. (BB/L000334/ 1) and A.E.F. (BB/J007072/1). Work in the Baulcombe laboratory is supported by The Gatsby Charitable Foundation and the European Research Council Advanced Investigator grant TRIBE. D.C.B. is the Royal Society Edward Penley Abraham Research Professor. We wish to thank Professor Stuart G. Siddell, University of Bristol, for providing the murine 17 clone 1 cellsThis is the final version of the article. It was first available from Cold Springs Harbor Press via http://dx.doi.org/10.1261/rna.052548.11
Discovery, Synthesis, and Optimization of Diarylisoxazole-3- carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore
This is the peer reviewed version of the following article: Roy, S., Šileikytė, J., Schiavone, M., Neuenswander, B., Argenton, F., Aubé, J., … Schoenen, F. J. (2015). Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore. ChemMedChem, 10(10), 1655–1671. http://doi.org/10.1002/cmdc.201500284, which has been published in final form at doi.org/10.1002/cmdc.201500284. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The mitochondrial permeability transition pore (mtPTP) is a Ca2+-requiring mega-channel which, under pathological conditions, leads to the deregulated release of Ca2+ and mitochondrial dysfunction, ultimately resulting in cell death. Although the mtPTP is a potential therapeutic target for many human pathologies, its potential as a drug target is currently unrealized. Herein we describe an optimization effort initiated around hit 1, 5-(3-hydroxyphenyl)-N-(3,4,5-trimethoxyphenyl)isoxazole-3-carboxamide, which was found to possess promising inhibitory activity against mitochondrial swelling (EC50 100 µm). This enabled the construction of a series of picomolar mtPTP inhibitors that also potently increase the calcium retention capacity of the mitochondria. Finally, the therapeutic potential and in vivo efficacy of one of the most potent analogues, N-(3-chloro-2-methylphenyl)-5-(4-fluoro-3-hydroxyphenyl)isoxazole-3-carboxamide (60), was validated in a biologically relevant zebrafish model of collagen VI congenital muscular dystrophies
Burkhardt-Cottingham sum rule and forward spin polarizabilities in Heavy Baryon Chiral Perturbation Theory
We study spin-dependent sum rules for forward virtual Compton
scattering(VVCS) off the nucleon in heavy baryon chiral perturbation theory at
order . We show how these sum rules can be evaluated from low energy
expansions (in the virtual photon energy) of the forward VVCS amplitudes. We
study in particular the Burkhardt -Cottingham sum rule in HBChPT and higher
terms in the low energy expansion, which can be related to the generalized
forward spin polarizabilities of the nucleon. The dependence of these
observables on the photon virtuality can be accessed, at small and
intermediate values, from existing and forthcoming data at Jefferson Lab.Comment: 16 pages,4 fig
Elastic electron deuteron scattering with consistent meson exchange and relativistic contributions of leading order
The influence of relativistic contributions to elastic electron deuteron
scattering is studied systematically at low and intermediate momentum transfers
( fm). In a -expansion, all leading order
relativistic -exchange contributions consistent with the Bonn OBEPQ models
are included. In addition, static heavy meson exchange currents including boost
terms and lowest order -currents are considered. Sizeable
effects from the various relativistic two-body contributions, mainly from
-exchange, have been found in form factors, structure functions and the
tensor polarization . Furthermore, static properties, viz. magnetic
dipole and charge quadrupole moments and the mean square charge radius are
evaluated.Comment: 15 pages Latex including 5 figures, final version accepted for
publication in Phys.Rev.C Details of changes: (i) The notation of the curves
in Figs. 1 and 2 have been clarified with respect to left and right panels.
(ii) In Figs. 3 and 4 an experimental point for T_20 has been added and a
corresponding reference [48] (iii) At the end of the text we have added a
paragraph concerning the quality of the Bonn OBEPQ potential
Dream-enactment behaviours during the COVID-19 pandemic: an international COVID-19 sleep study
There has been increasing concern about the long-term impact of coronavirus disease 2019 (COVID-19) as evidenced by anecdotal case reports of acute-onset parkinsonism and the polysomnographic feature of increased rapid eye movement sleep electromyographic activity. This study aimed to determine the prevalence and correlates of dream-enactment behaviours, a hallmark of rapid eye movement sleep behaviour disorder, which is a prodrome of α-synucleinopathy. This online survey was conducted between May and August 2020 in 15 countries/regions targeting adult participants (aged ≥18 years) from the general population with a harmonised structured questionnaire on sleep patterns and disorders, COVID-19 diagnosis and symptoms. We assessed dream-enactment behaviours using the Rapid Eye Movement Sleep Behaviour Disorder Single-Question Screen with an additional question on their frequency. Among 26,539 respondents, 21,870 (82.2%) answered all items that were analysed in this study (mean [SD] age 41.6 [15.8] years; female sex 65.5%). The weighted prevalence of lifetime and weekly dream-enactment behaviours was 19.4% and 3.1% and were found to be 1.8- and 2.9-times higher in COVID-19-positive cases, respectively. Both lifetime and weekly dream-enactment behaviours were associated with young age, male sex, smoking, alcohol consumption, higher physical activity level, nightmares, COVID-19 diagnosis, olfactory impairment, obstructive sleep apnea symptoms, mood, and post-traumatic stress disorder features. Among COVID-19-positive cases, weekly dream-enactment behaviours were positively associated with the severity of COVID-19. Dream-enactment behaviours are common among the general population during the COVID-19 pandemic and further increase among patients with COVID-19. Further studies are needed to investigate the potential neurodegenerative effect of COVID-19
Measurement of pion, kaon and proton production in proton-proton collisions at TeV
The measurement of primary , K, p and
production at mid-rapidity ( 0.5) in proton-proton collisions at
TeV performed with ALICE (A Large Ion Collider Experiment) at
the Large Hadron Collider (LHC) is reported. Particle identification is
performed using the specific ionization energy loss and time-of-flight
information, the ring-imaging Cherenkov technique and the kink-topology
identification of weak decays of charged kaons. Transverse momentum spectra are
measured from 0.1 up to 3 GeV/ for pions, from 0.2 up to 6 GeV/ for kaons
and from 0.3 up to 6 GeV/ for protons. The measured spectra and particle
ratios are compared with QCD-inspired models, tuned to reproduce also the
earlier measurements performed at the LHC. Furthermore, the integrated particle
yields and ratios as well as the average transverse momenta are compared with
results at lower collision energies.Comment: 33 pages, 19 captioned figures, 3 tables, authors from page 28,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/156
Ultrahigh Energy Cosmic Rays: The state of the art before the Auger Observatory
In this review we discuss the important progress made in recent years towards
understanding the experimental data on cosmic rays with energies \agt 10^{19}
eV. We begin with a brief survey of the available data, including a description
of the energy spectrum, mass composition, and arrival directions. At this point
we also give a short overview of experimental techniques. After that, we
introduce the fundamentals of acceleration and propagation in order to discuss
the conjectured nearby cosmic ray sources. We then turn to theoretical notions
of physics beyond the Standard Model where we consider both exotic primaries
and exotic physical laws. Particular attention is given to the role that
TeV-scale gravity could play in addressing the origin of the highest energy
cosmic rays. In the final part of the review we discuss the potential of future
cosmic ray experiments for the discovery of tiny black holes that should be
produced in the Earth's atmosphere if TeV-scale gravity is realized in Nature.Comment: Final version. To be published in Int. J. Mod. Phys.
Near-Infrared Properties of Metal-poor Globular Clusters in the Galactic Bulge Direction
Aims. J, H, and K' images obtained from the near-infrared imager CFHTIR on
the Canada-France-Hawaii Telescope are used to derive the morphological
parameters of the red giant branch (RGB) in the near-infrared color-magnitude
diagrams for 12 metal-poor globular clusters in the Galactic bulge direction.
Using the compiled data set of the RGB parameters for the observed 12 clusters,
in addition to the previously studied 5 clusters, we discuss the properties of
the RGB morphology for the clusters and compare them with the calibration
relations for the metal-rich bulge clusters and the metal-poor halo clusters.
Methods. The photometric RGB shape indices such as colors at fixed magnitudes
of MK = MH = (-5.5, -5, -4, and -3), magnitudes at fixed colors of (J - K)o =
(J - H)o = 0.7, and the RGB slope are measured from the fiducial normal points
defined in the near- infrared color-magnitude diagrams for each cluster. The
magnitudes of RGB bump and tip are also estimated from the differential and
cumulative luminosity functions of the selected RGB stars. The derived RGB
parameters have been used to examine the overall behaviors of the RGB
morphology as a function of cluster metallicity. Results. The correlations
between the near-infrared photometric RGB shape indices and the cluster
metallicity for the programme clusters compare favorably with the previous
observational calibration relations for metal-rich clusters in the Galactic
bulge and the metal-poor halo clusters. The observed near-infrared magnitudes
of the RGB bump and tip for the investigated clusters are also in accordance
with the previous calibration relations for the Galactic bulge clusters.Comment: 12 pages, 9 figures, accepted for publication in Astronomy &
Astrophysic
Flow Measurements via Two-particle Azimuthal Correlations in Au + Au Collisions at sqrt(s_NN) = 130 GeV
Two particle azimuthal correlation functions are presented for charged
hadrons produced in Au + Au collisions at RHIC sqrt(s_NN) = 130 GeV. The
measurements permit determination of elliptic flow without event-by-event
estimation of the reaction plane. The extracted elliptic flow values v_2 show
significant sensitivity to both the collision centrality and the transverse
momenta of emitted hadrons, suggesting rapid thermalization and relatively
strong velocity fields. When scaled by the eccentricity of the collision zone,
epsilon, the scaled elliptic flow shows little or no dependence on centrality
for charged hadrons with relatively low p_T. A breakdown of this epsilon
scaling is observed for charged hadrons with p_T > 1.0 GeV/c for the most
central collisions.Comment: 6 pages, RevTeX 3, 4 figures, 307 authors, submitted to Phys. Rev.
Lett. on 11 April 2002. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (will be made) publicly
available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
Net Charge Fluctuations in Au + Au Interactions at sqrt(s_NN) = 130 GeV
Data from Au + Au interactions at sqrt(s_NN) = 130 GeV, obtained with the
PHENIX detector at RHIC, are used to investigate local net charge fluctuations
among particles produced near mid-rapidity. According to recent suggestions,
such fluctuations may carry information from the Quark Gluon Plasma. This
analysis shows that the fluctuations are dominated by a stochastic distribution
of particles, but are also sensitive to other effects, like global charge
conservation and resonance decays.Comment: 6 pages, RevTeX 3, 3 figures, 307 authors, submitted to Phys. Rev.
Lett. on 21 March, 2002. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (will be made) publicly
available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
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