30 research outputs found
A Yersinia Effector with Enhanced Inhibitory Activity on the NF-ÎșB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages
A type III secretion system (T3SS) in pathogenic Yersinia
species functions to translocate Yop effectors, which modulate cytokine
production and regulate cell death in macrophages. Distinct pathways of
T3SS-dependent cell death and caspase-1 activation occur in
Yersinia-infected macrophages. One pathway of cell death
and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an
acetyltransferase that inactivates MAPK kinases and IKKÎČ to cause
TLR4-dependent apoptosis in naĂŻve macrophages. A YopJ isoform in Y.
pestis KIM (YopJKIM) has two amino acid substitutions,
F177L and K206E, not present in YopJ proteins of Y.
pseudotuberculosis and Y. pestis CO92. As compared
to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1
activation, and secretion of IL-1ÎČ in Yersinia-infected
macrophages. The molecular basis for increased apoptosis and activation of
caspase-1 by YopJKIM in Yersinia-infected
macrophages was studied. Site directed mutagenesis showed that the F177L and
K206E substitutions in YopJKIM were important for enhanced apoptosis,
caspase-1 activation, and IL-1ÎČ secretion. As compared to
YopJCO92, YopJKIM displayed an enhanced capacity to
inhibit phosphorylation of IÎșB-α in macrophages and to bind IKKÎČ in
vitro. YopJKIM also showed a moderately increased ability to inhibit
phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1ÎČ secretion
occurred in IKKÎČ-deficient macrophages infected with Y.
pestis expressing YopJCO92, confirming that the
NF-ÎșB pathway can negatively regulate inflammasome activation.
K+ efflux, NLRP3 and ASC were important for secretion of
IL-1ÎČ in response to Y. pestis KIM infection as shown using
macrophages lacking inflammasome components or by the addition of exogenous KCl.
These data show that caspase-1 is activated in naĂŻve macrophages in
response to infection with a pathogen that inhibits IKKÎČ and MAPK kinases
and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis
may represent an early innate immune response to highly virulent pathogens such
as Y. pestis KIM that have evolved an enhanced ability to
inhibit host signaling pathways
The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO2 measurements
During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO2 cycles from 48 European stations were available for 2017 and 2018.The UK sites were funded by the UK Department of Business,
Energy and Industrial Strategy (formerly the Department of Energy
and Climate Change) through contracts TRN1028/06/2015 and
TRN1537/06/2018. The stations at the ClimaDat Network in
Spain have received funding from the âla Caixaâ Foundation, under
agreement 2010-002624
On the computation of long period seismograms in a 3-D earth using normal mode based approximations
International audienceTomographic inversions for large-scale structure of the earth's mantle involve a forward modelling step of wave propagation through 3-D heterogeneity. Until now, most investigators have worked in the framework of the simplest theoretical assumptions, namely the infinite frequency 'ray theory' in the case of body wave traveltime inversions, or the 'path-average' approximation (PAVA) to normal mode perturbation theory, in the case of surface waves and long-period waveforms. As interest is shifting to mapping shorter wavelength structures, the need for a more accurate theoretical account of the interaction of seismic waves with mantle heterogeneity, coupled with improvements in path coverage, has been realized. Here we discuss different levels of approximations used in the context of normal mode perturbation theory, when modelling time domain seismic waveforms. We compare the performance of asymptotic approximations, which collapse the effects of 3-D structure onto the great circle vertical plane: the 1-D PAVA and a 2-D approximation called non-linear asymp-totic coupling theory (NACT), which both are zeroth order asymptotic approximations. We then discuss how off-vertical plane effects can be introduced using higher order asymptotics. These computationally efficient approximations are compared to the linear Born formalism (BORN), which computes scattering integrals over the entire surface of the sphere. We point out some limitations of this linear formalism in the case of spatially extended anomalies, and show how that can be remedied through the introduction of a non-linear term (NBORN). All these approximations are referenced to a precise 3-D numerical computation afforded by the spectral element method. We discuss simple geometries, and explore a range of sizes of anomalies compared to the wavelength of the seismic waves considered, thus illustrating the range of validity and limitations of the various approximations considered