288 research outputs found
The complement of protein kinases of the microsporidium Encephalitozoon cuniculi in relation to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe.
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Microsporidia, parasitic fungi-related eukaryotes infecting many cell types in a wide range of animals (including humans), represent a serious health threat in immunocompromised patients. The 2.9 Mb genome of the microsporidium Encephalitozoon cuniculi is the smallest known of any eukaryote. Eukaryotic protein kinases are a large superfamily of enzymes with crucial roles in most cellular processes, and therefore represent potential drug targets. We report here an exhaustive analysis of the E. cuniculi genomic database aimed at identifying and classifying all protein kinases of this organism with reference to the kinomes of two highly-divergent yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. RESULTS: A database search with a multi-level protein kinase family hidden Markov model library led to the identification of 29 conventional protein kinase sequences in the E. cuniculi genome, as well as 3 genes encoding atypical protein kinases. The microsporidian kinome presents striking differences from those of other eukaryotes, and this minimal kinome underscores the importance of conserved protein kinases involved in essential cellular processes. Approximately 30% of its kinases are predicted to regulate cell cycle progression while another approximately 28% have no identifiable homologues in model eukaryotes and are likely to reflect parasitic adaptations. E. cuniculi lacks MAP kinase cascades and almost all protein kinases that are involved in stress responses, ion homeostasis and nutrient signalling in the model fungi S. cerevisiae and S. pombe, including AMPactivated protein kinase (Snf1), previously thought to be ubiquitous in eukaryotes. A detailed database search and phylogenetic analysis of the kinomes of the two model fungi showed that the degree of homology between their kinomes of approximately 85% is much higher than that previously reported. CONCLUSION: The E. cuniculi kinome is by far the smallest eukaryotic kinome characterised to date. The difficulty in assigning clear homology relationships for nine out of the twentynine microsporidian conventional protein kinases despite its compact genome reflects the phylogenetic distance between microsporidia and other eukaryotes. Indeed, the E. cuniculi genome presents a high proportion of genes in which evolution has been accelerated by up to four-fold. There are no orthologues of the protein kinases that constitute MAP kinase pathways and many other protein kinases with roles in nutrient signalling are absent from the E. cuniculi kinome. However, orthologous kinases can nonetheless be identified that correspond to members of the yeast kinomes with roles in some of the most fundamental cellular processes. For example, E. cuniculi has clear orthologues of virtually all the major conserved protein kinases that regulate the core cell cycle machinery (Aurora, Polo, DDK, CDK and Chk1). A comprehensive comparison of the homology relationships between the budding and fission yeast kinomes indicates that, despite an estimated 800 million years of independent evolution, the two model fungi share approximately 85% of their protein kinases. This will facilitate the annotation of many of the as yet uncharacterised fission yeast kinases, and also those of novel fungal genomes.Published versio
Imaging the Renner-Teller effect using laser-induced electron diffraction
Structural information on electronically excited neutral molecules can be
indirectly retrieved, largely through pump-probe and rotational spectroscopy
measurements with the aid of calculations. Here, we demonstrate the direct
structural retrieval of neutral carbonyl disulfide (CS) in the BB
excited electronic state using laser-induced electron diffraction (LIED). We
unambiguously identify the ultrafast symmetric stretching and bending of the
field-dressed neutral CS molecule with combined picometer and attosecond
resolution using intrapulse pump-probe excitation and measurement. We invoke
the Renner-Teller effect to populate the BB excited state in neutral
CS, leading to bending and stretching of the molecule. Our results
demonstrate the sensitivity of LIED in retrieving the geometric structure of
CS, which is known to appear as a two-center scatterer
Down regulation of the high-affinity IgE receptor associated with successful treatment of chronic idiopathic urticaria with omalizumab
Chronic idiopathic urticaria is a condition that is often controllable with antihistamine therapy. However, some patients have disease burden that is difficult to manage, non-responsive to antihistamines and often requires immunosuppressive medications such as corticosteroids or cyclosporine. We present here a study that demonstrates the effectiveness of omalizumab in treating this condition and the temporal relationship between improvement and down regulation of the high affinity IgE receptor (FcΔRI). For this, blood samples were obtained from a symptomatic patient before each treatment and processed for flow cytometric analysis of FcΔRI levels on the surface of blood basophils. Down regulation of FcΔRI was observed in association with significant clinical improvement and discontinuation of immunosuppressive medications
Minimum length, extra dimensions, modified gravity and black hole remnants
We construct a Hilbert space representation of minimum-length deformed
uncertainty relation in presence of extra dimensions. Following this
construction, we study corrections to the gravitational potential (back
reaction on gravity) with the use of correspondingly modified propagator in
presence of two (spatial) extra dimensions. Interestingly enough, for the gravitational force approaches zero and the horizon for
modified Schwarzschild-Tangherlini space-time disappears when the mass
approaches quantum-gravity energy scale. This result points out to the
existence of zero-temperature black hole remnants in ADD brane-world model.Comment: 14 pages, 1 figure; Close to the version published in JCA
Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity
Glycosylated diazeniumdiolates of structure R2NN(O)dNO-R âČ (R âČ ) a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)dNO- ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)dNO-GlcNAc (where R2N) diethylamino or pyrrolidin-l-yl and GlcNAc) N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity
BVRI Light Curves for 29 Type Ia Supernovae
BVRI light curves are presented for 27 Type Ia supernovae discovered during
the course of the Calan/Tololo Survey and for two other SNe Ia observed during
the same period. Estimates of the maximum light magnitudes in the B, V, and I
bands and the initial decline rate parameter m15(B) are also given.Comment: 17 pages, figures and tables are not included (contact first author
if needed), to appear in the Astronomical Journa
Supersymmetric top and bottom squark production at hadron colliders
The scalar partners of top and bottom quarks are expected to be the lightest
squarks in supersymmetric theories, with potentially large cross sections at
hadron colliders. We present predictions for the production of top and bottom
squarks at the Tevatron and the LHC, including next-to-leading order
corrections in supersymmetric QCD and the resummation of soft gluon emission at
next-to-leading-logarithmic accuracy. We discuss the impact of the higher-order
corrections on total cross sections and transverse-momentum distributions, and
provide an estimate of the theoretical uncertainty due to scale variation and
the parton distribution functions.Comment: 29 pages, 6 figure
Gaugino production in proton-proton collisions at a center-of-mass energy of 8 TeV
Motivated by hints for a light Standard Model-like Higgs boson and a shift in
experimental attention towards electroweak supersymmetry particle production at
the CERN LHC, we update in this paper our precision predictions at
next-to-leading order of perturbative QCD matched to resummation at the
next-to-leading logarithmic accuracy for direct gaugino pair production in
proton-proton collisions with a center-of-mass energy of 8 TeV. Tables of total
cross sections are presented together with the corresponding scale and parton
density uncertainties for benchmark points adopted recently by the experimental
collaborations, and figures are presented for up-to-date model lines attached
to them. Since the experimental analyses are currently obtained with parton
showers matched to multi-parton matrix elements, we also analyze the precision
of this procedure by comparing invariant-mass and transverse-momentum
distributions obtained in this way to those obtained with threshold and
transverse-momentum resummation.Comment: 28 pages, 7 figures, 9 tables; version to appear in JHE
The primary cosmic ray composition between 10**15 and 10**16 eV from Extensive Air Showers electromagnetic and TeV muon data
The cosmic ray primary composition in the energy range between 10**15 and
10**16 eV, i.e., around the "knee" of the primary spectrum, has been studied
through the combined measurements of the EAS-TOP air shower array (2005 m
a.s.l., 10**5 m**2 collecting area) and the MACRO underground detector (963 m
a.s.l., 3100 m w.e. of minimum rock overburden, 920 m**2 effective area) at the
National Gran Sasso Laboratories. The used observables are the air shower size
(Ne) measured by EAS-TOP and the muon number (Nmu) recorded by MACRO. The two
detectors are separated on average by 1200 m of rock, and located at a
respective zenith angle of about 30 degrees. The energy threshold at the
surface for muons reaching the MACRO depth is approximately 1.3 TeV. Such muons
are produced in the early stages of the shower development and in a kinematic
region quite different from the one relevant for the usual Nmu-Ne studies. The
measurement leads to a primary composition becoming heavier at the knee of the
primary spectrum, the knee itself resulting from the steepening of the spectrum
of a primary light component (p, He). The result confirms the ones reported
from the observation of the low energy muons at the surface (typically in the
GeV energy range), showing that the conclusions do not depend on the production
region kinematics. Thus, the hadronic interaction model used (CORSIKA/QGSJET)
provides consistent composition results from data related to secondaries
produced in a rapidity region exceeding the central one. Such an evolution of
the composition in the knee region supports the "standard" galactic
acceleration/propagation models that imply rigidity dependent breaks of the
different components, and therefore breaks occurring at lower energies in the
spectra of the light nuclei.Comment: Submitted to Astroparticle Physic
Simplified Models for LHC New Physics Searches
This document proposes a collection of simplified models relevant to the
design of new-physics searches at the LHC and the characterization of their
results. Both ATLAS and CMS have already presented some results in terms of
simplified models, and we encourage them to continue and expand this effort,
which supplements both signature-based results and benchmark model
interpretations. A simplified model is defined by an effective Lagrangian
describing the interactions of a small number of new particles. Simplified
models can equally well be described by a small number of masses and
cross-sections. These parameters are directly related to collider physics
observables, making simplified models a particularly effective framework for
evaluating searches and a useful starting point for characterizing positive
signals of new physics. This document serves as an official summary of the
results from the "Topologies for Early LHC Searches" workshop, held at SLAC in
September of 2010, the purpose of which was to develop a set of representative
models that can be used to cover all relevant phase space in experimental
searches. Particular emphasis is placed on searches relevant for the first
~50-500 pb-1 of data and those motivated by supersymmetric models. This note
largely summarizes material posted at http://lhcnewphysics.org/, which includes
simplified model definitions, Monte Carlo material, and supporting contacts
within the theory community. We also comment on future developments that may be
useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results
from "Topologies for Early LHC Searches" workshop (SLAC, September 2010).
Supplementary material can be found at http://lhcnewphysics.or
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