394 research outputs found
Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy
We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin
Mutation in \u3ci\u3eATG5\u3c/i\u3e reduces autophagy and leads to ataxia with developmental delay
Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects’ cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health
Observation of the Crab Nebula with the HAWC Gamma-Ray Observatory
The Crab Nebula is the brightest TeV gamma-ray source in the sky and has been
used for the past 25 years as a reference source in TeV astronomy, for
calibration and verification of new TeV instruments. The High Altitude Water
Cherenkov Observatory (HAWC), completed in early 2015, has been used to observe
the Crab Nebula at high significance across nearly the full spectrum of
energies to which HAWC is sensitive. HAWC is unique for its wide field-of-view,
nearly 2 sr at any instant, and its high-energy reach, up to 100 TeV. HAWC's
sensitivity improves with the gamma-ray energy. Above 1 TeV the
sensitivity is driven by the best background rejection and angular resolution
ever achieved for a wide-field ground array.
We present a time-integrated analysis of the Crab using 507 live days of HAWC
data from 2014 November to 2016 June. The spectrum of the Crab is fit to a
function of the form . The data is well-fit with values of
, , and
log when
is fixed at 7 TeV and the fit applies between 1 and 37 TeV. Study of the
systematic errors in this HAWC measurement is discussed and estimated to be
50\% in the photon flux between 1 and 37 TeV.
Confirmation of the Crab flux serves to establish the HAWC instrument's
sensitivity for surveys of the sky. The HAWC survey will exceed sensitivity of
current-generation observatories and open a new view of 2/3 of the sky above 10
TeV.Comment: Submitted 2017/01/06 to the Astrophysical Journa
Daily monitoring of TeV gamma-ray emission from Mrk 421, Mrk 501, and the Crab Nebula with HAWC
We present results from daily monitoring of gamma rays in the energy range
to TeV with the first 17 months of data from the High
Altitude Water Cherenkov (HAWC) Observatory. Its wide field of view of 2
steradians and duty cycle of % are unique features compared to other TeV
observatories that allow us to observe every source that transits over HAWC for
up to hours each sidereal day. This regular sampling yields
unprecedented light curves from unbiased measurements that are independent of
seasons or weather conditions. For the Crab Nebula as a reference source we
find no variability in the TeV band. Our main focus is the study of the TeV
blazars Markarian (Mrk) 421 and Mrk 501. A spectral fit for Mrk 421 yields a
power law index and
an exponential cut-off
TeV. For Mrk 501, we find an index and exponential cut-off TeV. The light curves for both sources show clear
variability and a Bayesian analysis is applied to identify changes between flux
states. The highest per-transit fluxes observed from Mrk 421 exceed the Crab
Nebula flux by a factor of approximately five. For Mrk 501, several transits
show fluxes in excess of three times the Crab Nebula flux. In a comparison to
lower energy gamma-ray and X-ray monitoring data with comparable sampling we
cannot identify clear counterparts for the most significant flaring features
observed by HAWC.Comment: 18 pages, 10 figures, accepted for publication in The Astrophysical
Journa
The 2HWC HAWC Observatory Gamma Ray Catalog
We present the first catalog of TeV gamma-ray sources realized with the
recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the
most sensitive wide field-of-view TeV telescope currently in operation, with a
1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an
instantaneous field of view >1.5 sr and >90% duty cycle, it continuously
surveys and monitors the sky for gamma ray energies between hundreds GeV and
tens of TeV.
HAWC is located in Mexico at a latitude of 19 degree North and was completed
in March 2015. Here, we present the 2HWC catalog, which is the result of the
first source search realized with the complete HAWC detector. Realized with 507
days of data and represents the most sensitive TeV survey to date for such a
large fraction of the sky. A total of 39 sources were detected, with an
expected contamination of 0.5 due to background fluctuation. Out of these
sources, 16 are more than one degree away from any previously reported TeV
source. The source list, including the position measurement, spectrum
measurement, and uncertainties, is reported. Seven of the detected sources may
be associated with pulsar wind nebulae, two with supernova remnants, two with
blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa
Constraining the Ratio in TeV Cosmic Rays with Observations of the Moon Shadow by HAWC
An indirect measurement of the antiproton flux in cosmic rays is possible as
the particles undergo deflection by the geomagnetic field. This effect can be
measured by studying the deficit in the flux, or shadow, created by the Moon as
it absorbs cosmic rays that are headed towards the Earth. The shadow is
displaced from the actual position of the Moon due to geomagnetic deflection,
which is a function of the energy and charge of the cosmic rays. The
displacement provides a natural tool for momentum/charge discrimination that
can be used to study the composition of cosmic rays. Using 33 months of data
comprising more than 80 billion cosmic rays measured by the High Altitude Water
Cherenkov (HAWC) observatory, we have analyzed the Moon shadow to search for
TeV antiprotons in cosmic rays. We present our first upper limits on the
fraction, which in the absence of any direct measurements, provide
the tightest available constraints of on the antiproton fraction for
energies between 1 and 10 TeV.Comment: 10 pages, 5 figures. Accepted by Physical Review
All-particle cosmic ray energy spectrum measured by the HAWC experiment from 10 to 500 TeV
We report on the measurement of the all-particle cosmic ray energy spectrum
with the High Altitude Water Cherenkov (HAWC) Observatory in the energy range
10 to 500 TeV. HAWC is a ground based air-shower array deployed on the slopes
of Volcan Sierra Negra in the state of Puebla, Mexico, and is sensitive to
gamma rays and cosmic rays at TeV energies. The data used in this work were
taken from 234 days between June 2016 to February 2017. The primary cosmic-ray
energy is determined with a maximum likelihood approach using the particle
density as a function of distance to the shower core. Introducing quality cuts
to isolate events with shower cores landing on the array, the reconstructed
energy distribution is unfolded iteratively. The measured all-particle spectrum
is consistent with a broken power law with an index of prior to
a break at ) TeV, followed by an index of . The
spectrum also respresents a single measurement that spans the energy range
between direct detection and ground based experiments. As a verification of the
detector response, the energy scale and angular resolution are validated by
observation of the cosmic ray Moon shadow's dependence on energy.Comment: 16 pages, 11 figures, 4 tables, submission to Physical Review
- …