850 research outputs found
Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis
Neutrophils are potent effector cells and contain a battery of harmful substances and degrading enzymes. A silent neutrophil death, i.e., apoptosis, is therefore of importance to avoid damage to the surrounding tissue and to enable termination of the acute inflammatory process. There is a pile of evidence supporting the role for pro-inflammatory cytokines in extending the life-span of neutrophils, but relatively few studies have been devoted to mechanisms actively driving apoptosis induction in neutrophils. We have previously demonstrated that natural killer (NK) cells can promote apoptosis in healthy neutrophils. In this study, we set out to investigate how neutrophil sensitivity to NK cell-mediated cytotoxicity is regulated under inflammatory conditions. Using in vitro-activated neutrophils and a human skin chamber model that allowed collection of in vivo-transmigrated neutrophils, we performed a comprehensive characterization of neutrophil expression of ligands to NK cell receptors. These studies revealed a dramatic downregulation of HLA class I molecules in inflammatory neutrophils, which was associated with an enhanced susceptibility to NK cell cytotoxicity. Collectively, our data shed light on the complex regulation of interactions between NK cells and neutrophils during an inflammatory response and provide further support for a role of NK cells in the resolution phase of inflammation
Detailed Analysis of Nearby Bulgelike Dwarf Stars III. Alpha and Heavy-element abundances
The present sample of nearby bulgelike dwarf stars has kinematics and
metallicities characteristic of a probable inner disk or bulge origin. Ages
derived by using isochrones give 10-11 Gyr for these stars and metallicities
are in the range -0.80< [Fe/H]< +0.40. We calculate stellar parameters from
spectroscopic data, and chemical abundances of Mg, Si, Ca, Ti, La, Ba, Y, Zr
and Eu are derived by using spectrum synthesis.
We found that [alpha-elements/Fe] show different patterns depending on the
element. Si, Ca and Ti-to-iron ratios decline smoothly for increasing
metallicities, and follow essentially the disk pattern. O and Mg, products of
massive supernovae, and also the r-process element Eu, are overabundant
relative to disk stars, showing a steeper decline for metallicities [Fe/H] >
-0.3 dex. [s-elements/Fe] roughly track the solar values with no apparent trend
with metallicity for [Fe/H] < 0, showing subsolar values for the metal rich
stars. Both kinematical and chemical properties of the bulgelike stars indicate
a distinct identity of this population when compared to disk stars.Comment: 21 pages, 9 figures, to appear in Ap
Measurement of proton electromagnetic form factors in in the energy region 2.00-3.08 GeV
The process of is studied at 22 center-of-mass
energy points () from 2.00 to 3.08 GeV, exploiting 688.5~pb of
data collected with the BESIII detector operating at the BEPCII collider. The
Born cross section~() of is
measured with the energy-scan technique and it is found to be consistent with
previously published data, but with much improved accuracy. In addition, the
electromagnetic form-factor ratio () and the value of the
effective (), electric () and magnetic () form
factors are measured by studying the helicity angle of the proton at 16
center-of-mass energy points. and are determined with
high accuracy, providing uncertainties comparable to data in the space-like
region, and is measured for the first time. We reach unprecedented
accuracy, and precision results in the time-like region provide information to
improve our understanding of the proton inner structure and to test theoretical
models which depend on non-perturbative Quantum Chromodynamics
Search for the decay
We search for radiative decays into a weakly interacting neutral
particle, namely an invisible particle, using the produced through the
process in a data sample of
decays collected by the BESIII detector
at BEPCII. No significant signal is observed. Using a modified frequentist
method, upper limits on the branching fractions are set under different
assumptions of invisible particle masses up to 1.2 . The upper limit corresponding to an invisible particle with zero mass
is 7.0 at the 90\% confidence level
First observations of hadrons
Based on events collected with
the BESIII detector, five hadronic decays are searched for via process
. Three of them, ,
, and are observed for the first
time, with statistical significances of 7.4, , and
9.1, and branching fractions of ,
, and ,
respectively, where the first uncertainties are statistical and the second
systematic. No significant signal is observed for the other two decay modes,
and the corresponding upper limits of the branching fractions are determined to
be and at 90% confidence level.Comment: 17 pages, 16 figure
Precise Measurements of Branching Fractions for Meson Decays to Two Pseudoscalar Mesons
We measure the branching fractions for seven two-body decays to
pseudo-scalar mesons, by analyzing data collected at
GeV with the BESIII detector at the BEPCII collider. The branching fractions
are determined to be ,
,
,
,
,
,
,
where the first uncertainties are statistical, the second are systematic, and
the third are from external input branching fraction of the normalization mode
. Precision of our measurements is significantly improved
compared with that of the current world average values
Measurements of Weak Decay Asymmetries of , , , and
Using production from a 567 pb
data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried
out simultaneously on the four decay modes of , , , and . For the first time, the
transverse polarization is studied in unpolarized
collisions, where a non-zero effect is observed with a statistical significance
of 2.1. The decay asymmetry parameters of the weak
hadronic decays into , , and
are measured to be ,
,
, and
, respectively. In comparison with
previous results, the measurements for the and
modes are consistent but with improved precision, while the parameters for the
and modes are measured for the first time
Proteolytic Processing of Nlrp1b Is Required for Inflammasome Activity
Nlrp1b is a NOD-like receptor that detects the catalytic activity of anthrax lethal toxin and subsequently co-oligomerizes into a pro-caspase-1 activation platform known as an inflammasome. Nlrp1b has two domains that promote oligomerization: a NACHT domain, which is a member of the AAA+ ATPase family, and a poorly characterized Function to Find Domain (FIIND). Here we demonstrate that proteolytic processing within the FIIND generates N-terminal and C-terminal cleavage products of Nlrp1b that remain associated in both the auto-inhibited state and in the activated state after cells have been treated with lethal toxin. Functional significance of cleavage was suggested by the finding that mutations that block processing of Nlrp1b also prevent the ability of Nlrp1b to activate pro-caspase-1. By using an uncleaved mutant of Nlrp1b, we established the importance of cleavage by inserting a heterologous TEV protease site into the FIIND and demonstrating that TEV protease processed this site and induced inflammasome activity. Proteolysis of Nlrp1b was shown to be required for the assembly of a functional inflammasome: a mutation within the FIIND that abolished cleavage had no effect on self-association of a FIIND-CARD fragment, but did reduce the recruitment of pro-caspase-1. Our work indicates that a post-translational modification enables Nlrp1b to function
The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains
BACKGROUND:Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis". METHODOLOGY/PRINCIPAL FINDINGS:Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains. CONCLUSIONS/SIGNIFICANCE:The better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we showed that the membrane targets for these molecules are preferentially the fluid membrane domains and that the mechanism involves the induction of membrane negative curvature. Consequences on cellular uptake are discussed
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