363 research outputs found
Automated glycan assembly of <sup>19</sup>F labelled glycan probes enables highâthroughput NMR studies of proteinâglycan interactions
Proteinâglycan interactions mediate important biological processes, including pathogen host invasion and cellular communication. Major challenges to monitoring these low affinity interactions are the required high sensitivity of a biophysical assay and to cover a breath of synthetic wellâdefined structures. Here, we showcase an expedite approach that integrates automated glycan assembly (AGA) of 19 F labelled probes and highâthroughput NMR methods, enabling the study of proteinâglycan interactions. Synthetic Lewis type 2 antigens were screened against seven glycan binding proteins (GBPs), including DCâSIGN and BambL, respectively involved in HIVâ1 and lung infections in immunocompromised patients, confirming the preference for fucosylated glycans (Le x , H type 2, Le y ). Previously unknown glycanâlectin weak interactions were detected, and thermodynamic data were obtained. Enzymatic reactions were monitored in realâtime, delivering kinetic parameters. These results demonstrate the utility of AGA combined with 19 F NMR for the discovery and characterization of glycanâprotein interactions, opening up new perspectives for 19 F labelled complex glycans
Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: A case-control study
Objective: To assess the role of foot dermatomycosis ( tinea pedis and onychomycosis) and other candidate risk factors in the development of acute bacterial cellulitis of the leg. Methods: A case-control study, including 243 patients ( cases) with acute bacterial cellulitis of the leg and 467 controls, 2 per case, individually matched for gender, age (+/-5 years), hospital and admission date (+/-2 months). Results: Overall, mycology-proven foot dermatomycosis was a significant risk factor for acute bacterial cellulitis (odds ratio, OR: 2.4; p < 0.001), as were tinea pedis interdigitalis (OR: 3.2; p < 0.001), tinea pedis plantaris (OR: 1.7; p = 0.005) and onychomycosis (OR: 2.2; p < 0.001) individually. Other risk factors included: disruption of the cutaneous barrier, history of bacterial cellulitis, chronic venous insufficiency and leg oedema. Conclusions: Tinea pedis and onychomycosis were found to be significant risk factors for acute bacterial cellulitis of the leg that are readily amenable to treatment with effective pharmacological therapy. Copyright (C) 2004 S. Karger AG, Basel
Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate
The H3+ molecular ion plays a fundamental role in interstellar chemistry, as
it initiates a network of chemical reactions that produce many interstellar
molecules. In dense clouds, the H3+ abundance is understood using a simple
chemical model, from which observations of H3+ yield valuable estimates of
cloud path length, density, and temperature. On the other hand, observations of
diffuse clouds have suggested that H3+ is considerably more abundant than
expected from the chemical models. However, diffuse cloud models have been
hampered by the uncertain values of three key parameters: the rate of H3+
destruction by electrons, the electron fraction, and the cosmic-ray ionisation
rate. Here we report a direct experimental measurement of the H3+ destruction
rate under nearly interstellar conditions. We also report the observation of
H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is
already known. Taken together, these results allow us to derive the value of
the third uncertain model parameter: we find that the cosmic-ray ionisation
rate in this sightline is forty times faster than previously assumed. If such a
high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy
between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres
A remote secondary binding pocket promotes heteromultivalent targeting of DC-SIGN
Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGNâs carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general
Detection of very high energy gamma-ray emission from the gravitationally-lensed blazar QSO B0218+357 with the MAGIC telescopes
Context. QSO B0218+357 is a gravitationally lensed blazar located at a
redshift of 0.944. The gravitational lensing splits the emitted radiation into
two components, spatially indistinguishable by gamma-ray instruments, but
separated by a 10-12 day delay. In July 2014, QSO B0218+357 experienced a
violent flare observed by the Fermi-LAT and followed by the MAGIC telescopes.
Aims. The spectral energy distribution of QSO B0218+357 can give information on
the energetics of z ~ 1 very high energy gamma- ray sources. Moreover the
gamma-ray emission can also be used as a probe of the extragalactic background
light at z ~ 1. Methods. MAGIC performed observations of QSO B0218+357 during
the expected arrival time of the delayed component of the emission. The MAGIC
and Fermi-LAT observations were accompanied by quasi-simultaneous optical data
from the KVA telescope and X-ray observations by Swift-XRT. We construct a
multiwavelength spectral energy distribution of QSO B0218+357 and use it to
model the source. The GeV and sub-TeV data, obtained by Fermi-LAT and MAGIC,
are used to set constraints on the extragalactic background light. Results.
Very high energy gamma-ray emission was detected from the direction of QSO
B0218+357 by the MAGIC telescopes during the expected time of arrival of the
trailing component of the flare, making it the farthest very high energy
gamma-ray sources detected to date. The observed emission spans the energy
range from 65 to 175 GeV. The combined MAGIC and Fermi-LAT spectral energy
distribution of QSO B0218+357 is consistent with current extragalactic
background light models. The broad band emission can be modeled in the
framework of a two zone external Compton scenario, where the GeV emission comes
from an emission region in the jet, located outside the broad line region.Comment: 11 pages, 6 figures, accepted for publication in A&
Long-term multi-wavelength variability and correlation study of Markarian 421 from 2007 to 2009
We study the multi-band variability and correlations of the TeV blazar Mrk
421 on year time scales, which can bring additional insight on the processes
responsible for its broadband emission. We observed Mrk 421 in the very high
energy (VHE) gamma-ray range with the Cherenkov telescope MAGIC-I from March
2007 to June 2009 for a total of 96 hours of effective time after quality cuts.
The VHE flux variability is quantified with several methods, including the
Bayesian Block algorithm, which is applied to data from Cherenkov telescopes
for the first time. The 2.3 year long MAGIC light curve is complemented with
data from the Swift/BAT and RXTE/ASM satellites and the KVA, GASP-WEBT, OVRO,
and Mets\"ahovi telescopes from February 2007 to July 2009, allowing for an
excellent characterisation of the multi-band variability and correlations over
year time scales. Mrk 421 was found in different gamma-ray emission states
during the 2.3 year long observation period. Flares and different levels of
variability in the gamma-ray light curve could be identified with the Bayesian
Block algorithm. The same behaviour of a quiet and active emission was found in
the X-ray light curves measured by Swift/BAT and the RXTE/ASM, with a direct
correlation in time. The behaviour of the optical light curve of GASP-WEBT and
the radio light curves by OVRO and Mets\"ahovi are different as they show no
coincident features with the higher energetic light curves and a less variable
emission. The fractional variability is overall increasing with energy. The
comparable variability in the X-ray and VHE bands and their direct correlation
during both high- and low-activity periods spanning many months show that the
electron populations radiating the X-ray and gamma-ray photons are either the
same, as expected in the Synchrotron-Self-Compton mechanism, or at least
strongly correlated, as expected in electromagnetic cascades.Comment: Corresponding authors: Ann-Kristin Overkemping
([email protected]), Marina Manganaro
([email protected]), Diego Tescaro ([email protected]), To be published
in Astronomy&Astrophysics (A&A), 12 pages, 9 figure
Investigating the peculiar emission from the new VHE gamma-ray source H1722+119
The MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes observed
the BL Lac object H1722+119 (redshift unknown) for six consecutive nights
between 2013 May 17 and 22, for a total of 12.5 h. The observations were
triggered by high activity in the optical band measured by the KVA (Kungliga
Vetenskapsakademien) telescope. The source was for the first time detected in
the very high energy (VHE, GeV) -ray band with a statistical
significance of 5.9 . The integral flux above 150 GeV is estimated to
be per cent of the Crab Nebula flux. We used contemporaneous
high energy (HE, 100 MeV GeV) -ray observations from
Fermi-LAT (Large Area Telescope) to estimate the redshift of the source. Within
the framework of the current extragalactic background light models, we estimate
the redshift to be . Additionally, we used contemporaneous
X-ray to radio data collected by the instruments on board the Swift satellite,
the KVA, and the OVRO (Owens Valley Radio Observatory) telescope to study
multifrequency characteristics of the source. We found no significant temporal
variability of the flux in the HE and VHE bands. The flux in the optical and
radio wavebands, on the other hand, did vary with different patterns. The
spectral energy distribution (SED) of H1722+119 shows surprising behaviour in
the Hz frequency range. It can be modelled
using an inhomogeneous helical jet synchrotron self-Compton model.Comment: 12 pages, 5 figures, 2 table
Multi-Wavelength Observations of the Blazar 1ES 1011+496 in Spring 2008
The BL Lac object 1ES 1011+496 was discovered at Very High Energy gamma-rays
by MAGIC in spring 2007. Before that the source was little studied in different
wavelengths. Therefore a multi-wavelength (MWL) campaign was organized in
spring 2008. Along MAGIC, the MWL campaign included the Metsahovi radio
observatory, Bell and KVA optical telescopes and the Swift and AGILE
satellites. MAGIC observations span from March to May, 2008 for a total of 27.9
hours, of which 19.4 hours remained after quality cuts. The light curve showed
no significant variability. The differential VHE spectrum could be described
with a power-law function. Both results were similar to those obtained during
the discovery. Swift XRT observations revealed an X-ray flare, characterized by
a harder when brighter trend, as is typical for high synchrotron peak BL Lac
objects (HBL). Strong optical variability was found during the campaign, but no
conclusion on the connection between the optical and VHE gamma-ray bands could
be drawn. The contemporaneous SED shows a synchrotron dominated source, unlike
concluded in previous work based on nonsimultaneous data, and is well described
by a standard one zone synchrotron self Compton model. We also performed a
study on the source classification. While the optical and X-ray data taken
during our campaign show typical characteristics of an HBL, we suggest, based
on archival data, that 1ES 1011+496 is actually a borderline case between
intermediate and high synchrotron peak frequency BL Lac objects.Comment: 13 pages, accepted for publication in MNRA
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