942 research outputs found
Zinc depletion regulates the processing and secretion of IL-1β.
Sterile inflammation contributes to many common and serious human diseases. The pro-inflammatory cytokine interleukin-1β (IL-1β) drives sterile inflammatory responses and is thus a very attractive therapeutic target. Activation of IL-1β in sterile diseases commonly requires an intracellular multi-protein complex called the NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome. A number of disease-associated danger molecules are known to activate the NLRP3 inflammasome. We show here that depletion of zinc from macrophages, a paradigm for zinc deficiency, also activates the NLRP3 inflammasome and induces IL-1β secretion. Our data suggest that zinc depletion damages the integrity of lysosomes and that this event is important for NLRP3 activation. These data provide new mechanistic insight to how zinc deficiency contributes to inflammation and further unravel the mechanisms of NLRP3 inflammasome activation
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness
Voriconazole is a triazole antifungal agent recommended as primary treatment for invasive aspergillosis, as well as some other mold infections. However, it presents some pharmacokinetic singularities that lead to a great variability intra- and interindividually, nonlinear pharmacokinetics, and a narrow therapeutic range. Most experts have recommended tracing the levels of voriconazole in patients when receiving treatment. This azole is metabolized through the hepatic enzyme complex cytochrome P450 (CYPP450), with the isoenzyme CYP2C19 being principally involved. Allelic variations (polymorphisms) of the gene that encodes this enzyme are known to contribute to variability in voriconazole exposure. Three different allelic variants, CYP2C19*17, CYP2C19*2, and CYP2C19*3, could explain most of the phenotypes related to the voriconazole metabolism and some of its pharmacokinetic singularities. We designed a rapid molecular method based on high-resolution melting to characterize these polymorphisms in a total of 142 samples, avoiding sequencing. Three PCRs were designed with similar cycling conditions to run simultaneously. The results showed that our method represents a fast, accurate, and inexpensive means to study these variants related to voriconazole metabolism. In clinical practice, this could offer a useful tool to individually optimize therapy and reduce expenses in patients with fungal infections.National Institute of Health Carlos III (AES13PI13/01817Research Project MPY 1367/13). L.B.-M. has a contract supported by theMinisterio de Ciencia e Innovación, Instituto de Salud Carlos III, cofinanced by the EuropeanDevelopment Regional Fund (EDRF) “A Way to Achieve Europe” and the SpanishNetwork for the Research in Infectious Diseases (REIPI; RD12/0015/0015). B.M.-R. is astudent in the Master’s Program entitled “Microbiología Aplicada a la Salud Pública eInvestigación en Enfermedades Infecciosas,” Alcalá de Henares University, Madrid,Spain. A.C. and C.C. were supported by the Northern Portugal Regional OperationalProgram (NORTE 2020) under the Portugal 2020 Partnership Agreement through theEuropean Regional Development Fund (FEDER; NORTE-01-0145-FEDER-000013) and theFundação Para a Ciência e Tecnologia (FCT; IF/00735/2014 [A.C.] and SFRH/BPD/96176/2013 [C.C.])
Conformal TiO aerogel-like films by plasma deposition: from omniphobic antireflective coatings to perovskite solar cells photoelectrodes
The ability to control porosity in oxide thin films is one of the key factors
that determine their properties. Despite the abundance of dry processes for the
synthesis of oxide porous layers, the high porosity range is typically achieved
by spin-coating-based wet chemical methods. Besides, special techniques such as
supercritical drying are required to replace the pore liquid with air while
maintaining the porous network. In this study, we propose a new method for the
fabrication of ultra-porous titanium dioxide thin films at room or mild
temperatures (T lower or equal to 120 degrees Celsius) by the sequential
process involving plasma deposition and etching. These films are conformal to
the substrate topography even for high-aspect-ratio substrates and show
percolated porosity values above 85 percent that are comparable to advanced
aerogels. The films deposited at room temperature are amorphous. However, they
become partly crystalline at slightly higher temperatures presenting a
distribution of anatase clusters embedded in the sponge-like structure.
Surprisingly, the porous structure remains after annealing the films at 450
degrees Celsius in air, which increases the fraction of the embedded anatase
nanocrystals. The films are antireflective, omniphobic, and photoactive
becoming super-hydrophilic subjected to UV light irradiation The supported
percolated nanoporous structure can be used as an electron-conducting electrode
in perovskite solar cells. The properties of the cells depend on the aerogel
film thickness reaching efficiencies close to those of commercial mesoporous
anatase electrodes. This generic solvent-free synthesis is scalable and is
applicable to ultra-high porous conformal oxides of different compositions with
potential applications in photonics, optoelectronics, energy storage, and
controlled wetting.Comment: 31 pages, 10 Figs. plus Supporting Information 7 pags, 6 figs. Full
Pape
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider
Measurements of multi-particle azimuthal correlations (cumulants) for charged
particles in p-Pb and Pb-Pb collisions are presented. They help address the
question of whether there is evidence for global, flow-like, azimuthal
correlations in the p-Pb system. Comparisons are made to measurements from the
larger Pb-Pb system, where such evidence is established. In particular, the
second harmonic two-particle cumulants are found to decrease with multiplicity,
characteristic of a dominance of few-particle correlations in p-Pb collisions.
However, when a gap is placed to suppress such correlations,
the two-particle cumulants begin to rise at high-multiplicity, indicating the
presence of global azimuthal correlations. The Pb-Pb values are higher than the
p-Pb values at similar multiplicities. In both systems, the second harmonic
four-particle cumulants exhibit a transition from positive to negative values
when the multiplicity increases. The negative values allow for a measurement of
to be made, which is found to be higher in Pb-Pb collisions at
similar multiplicities. The second harmonic six-particle cumulants are also
found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find
which is indicative of a Bessel-Gaussian
function for the distribution. For very high-multiplicity Pb-Pb
collisions, we observe that the four- and six-particle cumulants become
consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and
Pb-Pb are measured. These are found to be similar for overlapping
multiplicities, when a gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE
In this small note we are concerned with the solution of Forward-Backward
Stochastic Differential Equations (FBSDE) with drivers that grow quadratically
in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem
is a comparison result that allows comparing componentwise the signs of the
control processes of two different qgFBSDE. As a byproduct one obtains
conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio
- …