808 research outputs found
Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages
Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing of bacteria are interrelated functions essential for bacterial clearance but the rate-limiting step when macrophages are challenged with large numbers of the major medical pathogen Staphylococcus aureus is unknown. We show that macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S. aureus (Newman, SH1000 and USA300 strains). S. aureus ingestion by macrophages is associated with a rapid decline in bacterial viability immediately after phagocytosis. However, not all bacteria are killed in the phagolysosome, and we demonstrate reduced acidification of the phagolysosome, associated with failure of phagolysosomal maturation and reduced activation of cathepsin D. This results in accumulation of viable intracellular bacteria in macrophages. We show macrophages fail to engage apoptosis-associated bacterial killing. Ultittop mately macrophages with viable bacteria undergo cell lysis, and viable bacteria are released and can be internalized by other macrophages. We show that cycles of lysis and reuptake maintain a pool of viable intracellular bacteria over time when killing is overwhelmed and demonstrate intracellular persistence in alveolar macrophages in the lungs in a murine model
No Go Theorem for Kinematic Self-Similarity with A Polytropic Equation of State
We have investigated spherically symmetric spacetimes which contain a perfect
fluid obeying the polytropic equation of state and admit a kinematic
self-similar vector of the second kind which is neither parallel nor orthogonal
to the fluid flow. We have assumed two kinds of polytropic equations of state
and shown in general relativity that such spacetimes must be vacuum.Comment: 5 pages, no figures. Revtex. One word added to the title. Final
version to appear in Physical Review D as a Brief Repor
SRAO CO Observation of 11 Supernova Remnants in l = 70 to 190 deg
We present the results of 12CO J = 1-0 line observations of eleven Galactic
supernova remnants (SNRs) obtained using the Seoul Radio Astronomy Observatory
(SRAO) 6-m radio telescope. The observation was made as a part of the SRAO CO
survey of SNRs between l = 70 and 190 deg, which is intended to identify SNRs
interacting with molecular clouds. The mapping areas for the individual SNRs
are determined to cover their full extent in the radio continuum. We used
halfbeam grid spacing (60") for 9 SNRs and full-beam grid spacing (120") for
the rest. We detected CO emission towards most of the remnants. In six SNRs,
molecular clouds showed a good spatial relation with their radio morphology,
although no direct evidence for the interaction was detected. Two SNRs are
particularly interesting: G85.4+0.7, where there is a filamentary molecular
cloud along the radio shell, and 3C434.1, where a large molecular cloud appears
to block the western half of the remnant. We briefly summarize the results
obtained for individual SNRs.Comment: Accepted for publication in Astrophysics & Space Science. 12 pages,
12 figures, and 3 table
The Biogenetic Origin of the Biologically Active Naematolin of Hypholoma Species Involves an Unusual Sesquiterpene Synthase
Naematolin is a biologically active sesquiterpene produced by Hypholoma species. Low titres and complex structure constrain the exploitation of this secondary metabolite. Here, we de novo sequenced the H. fasciculare genome to identify a candidate biosynthetic gene cluster for production of naematolin. Using Aspergillus oryzae as a heterologous host for gene expression, the activity of several sesquiterpene synthases were investigated, highlighting one atypical sesquiterpene synthase apparently capable of catalysing the 1,11 and subsequent 2,10 ring closures, which primes the synthesis of the distinctive structure of caryophyllene derivatives. Co-expression of the cyclase with an FAD oxidase adjacent within the gene cluster generated four oxidised caryophyllene-based sesquiterpenes: 5β,6α,8β-trihydroxycariolan, 5β,8β-dihydroxycariolan along with two previously unknown caryophyllene derivatives 2 and 3. This represents the first steps towards heterologous production of such basidiomycete-derived caryophyllene-based sesquiterpenes, opening a venue for potential novel antimicrobials via combinatorial biosynthesis
Changes in the ceIl membrane of Lactobacillus bulgaricus during storage following freeze-drying
The mechanism of inactivation of freeze-dried Lactobacillus bulgaricus during storage in maltodextrin under controlled humidity was investigated. Evidence is presented supporting the hypothesis that membrane damage occurs during storage. A study on the lipid composition of the cells by gas chromatography showed a decrease in the unsaturated and saturated fatty acid content of the cell. Further evidence indicating membrane damage includes a decrease in membrane bound proton-translocating ATPase activity
Measurement of (anti)deuteron and (anti)proton production in DIS at HERA
The first observation of (anti)deuterons in deep inelastic scattering at HERA
has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV
using an integrated luminosity of 120 pb-1. The measurement was performed in
the central rapidity region for transverse momentum per unit of mass in the
range 0.3<p_T/M<0.7. The particle rates have been extracted and interpreted in
terms of the coalescence model. The (anti)deuteron production yield is smaller
than the (anti)proton yield by approximately three orders of magnitude,
consistent with the world measurements.Comment: 26 pages, 9 figures, 5 tables, submitted to Nucl. Phys.
Observation of isolated high-E_T photons in deep inelastic scattering
First measurements of cross sections for isolated prompt photon production in
deep inelastic ep scattering have been made using the ZEUS detector at the HERA
electron-proton collider using an integrated luminosity of 121 pb^-1. A signal
for isolated photons in the transverse energy and rapidity ranges 5 < E_T^gamma
< 10 GeV and -0.7 < eta^gamma < 0.9 was observed for virtualities of the
exchanged photon of Q^2 > 35 GeV^2. Cross sections are presented for inclusive
prompt photons and for those accompanied by a single jet in the range E_T^jet
\geq 6 GeV and -1.5 \leq eta^jet < 1.8. Calculations at order alpha^3alpha_s
describe the data reasonably well.Comment: 16 pages, 5 figure
Photoproduction of mesons associated with a leading neutron
The photoproduction of mesons associated with a leading
neutron has been observed with the ZEUS detector in collisions at HERA
using an integrated luminosity of 80 pb. The neutron carries a large
fraction, {}, of the incoming proton beam energy and is detected at
very small production angles, { mrad}, an indication of
peripheral scattering. The meson is centrally produced with
pseudorapidity {
GeV}, which is large compared to the average transverse momentum of the neutron
of 0.22 GeV. The ratio of neutron-tagged to inclusive production is
in the photon-proton
center-of-mass energy range { GeV}. The data suggest that the
presence of a hard scale enhances the fraction of events with a leading neutron
in the final state.Comment: 28 pages, 4 figures, 2 table
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