A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB 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 IKKβ to cause TLR4-dependent apoptosis in naïve 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-1β 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-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β 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 naïve macrophages in response to infection with a pathogen that inhibits IKKβ 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 ‘la Caixa’ Foundation, under agreement 2010-002624

P and S tomography using normal-mode and surface waves data with a neighbourhood algorithm

Traditionally P- and S-wave tomography has been based on the inversion of data that are sensitive to the desired Earth structure, and model covariance is estimated from imperfect resolution and data error propagation. This analysis ignores the usually large null-spaces, and hence the significant non-uniqueness of the solution encountered in seismic tomography problems. Here we perform a model space search for P- and S-velocity structure to find acceptable fits to recent normal-mode splitting and fundamental-mode phase velocity data. The survey of the model space employs the neighbourhood algorithm of Sambridge, which preferentially samples the good data-fitting regions. A Bayesian approach is used subsequently to extract robust information from the ensemble of models. We particularly focus on posterior marginal probability density functions and covariances for the various model parameters. The covariance matrix obtained is very useful in providing insights into the trade-offs between the different variables and the uncertainties associated with them. We stay within the framework of perturbation theory, meaning that our emphasis is on the null-space of the linear inverse problem rather than the neglected non-linearity. The whole model space (including the null-space) is sampled within reasonable parameter bounds, and hence the error bars are determined by all fitting models rather than subjective prior information. We estimated P and S models for spherical harmonic degree two only. The uncertainties are quite large and corresponding relative errors can exceed 100 per cent in the mid-mantle for V . We find a good correlation of our most likely S model with previous models but some small changes in amplitude. Our most likely P model differs quite strongly from the recent P model SB10L 18 and the correlation between our most likely P and S models is small. Among all the good data-fitting models, there are, however, many that have a significant V - V correlation. We compute d In V /d In V from the models that correlate significantly. We find an increase with depth in the top 1500 km. Deeper in the mantle, normal-mode data prefer modest values compared with traveltime data. p p s s

P and S tomography using normal-mode and surface waves data with a neighbourhood algorithm

Traditionally P- and S-wave tomography has been based on the inversion of data that are sensitive to the desired Earth structure, and model covariance is estimated from imperfect resolution and data error propagation. This analysis ignores the usually large null-spaces, and hence the significant non-uniqueness of the solution encountered in seismic tomography problems. Here we perform a model space search for P- and S-velocity structure to find acceptable fits to recent normal-mode splitting and fundamental-mode phase velocity data. The survey of the model space employs the neighbourhood algorithm of Sambridge, which preferentially samples the good data-fitting regions. A Bayesian approach is used subsequently to extract robust information from the ensemble of models. We particularly focus on posterior marginal probability density functions and covariances for the various model parameters. The covariance matrix obtained is very useful in providing insights into the trade-offs between the different variables and the uncertainties associated with them. We stay within the framework of perturbation theory, meaning that our emphasis is on the null-space of the linear inverse problem rather than the neglected non-linearity. The whole model space (including the null-space) is sampled within reasonable parameter bounds, and hence the error bars are determined by all fitting models rather than subjective prior information. We estimated P and S models for spherical harmonic degree two only. The uncertainties are quite large and corresponding relative errors can exceed 100 per cent in the mid-mantle for Vp. We find a good correlation of our most likely S model with previous models but some small changes in amplitude. Our most likely P model differs quite strongly from the recent P model SB10L 18 and the correlation between our most likely P and S models is small. Among all the good data-fitting models, there are, however, many that have a significant Vp - Vs correlation. We compute d In Vs/d In Vp from the models that correlate significantly. We find an increase with depth in the top 1500 km. Deeper in the mantle, normal-mode data prefer modest values compared with traveltime data

The signal of mantle anisotropy in the coupling of normal modes

We investigate whether the coupling of normal mode (NM) multiplets can help us constrain mantle anisotropy. We first derive explicit expressions of the generalized structure coefficients of coupled modes in terms of elastic coefficients, including the Love parameters describing radial anisotropy and the parameters describing azimuthal anisotropy (J , J , K , K , M , M , B , B , G , G , E , E , H , H , D and D ). We detail the selection rules that describe which modes can couple together and which elastic parameters govern their coupling. We then focus on modes of type S T and determine whether they can be used to constrain mantle anisotropy. We show that they are sensitive to six elastic parameters describing azimuthal anisotropy, in addition to the two shear-wave elastic parameters L and N (i.e. V and V ). We find that neither isotropic nor radially anisotropic mantle models can fully explain the observed degree two signal. We show that the NM signal that remains after correction for the effect of the crust and mantle radial anisotropy can be explained by the presence of azimuthal anisotropy in the upper mantle. Although the data favour locating azimuthal anisotropy below 400km, its depth extent and distribution is still not well constrained by the data. Consideration of NM coupling can thus help constrain azimuthal anisotropy in the mantle, but joint analyses with surface-wave phase velocities is needed to reduce the parameter trade-offs and improve our constraints on the individual elastic parameters and the depth location of the azimuthal anisotropy. © 2008 The Authors Journal compilation © 2008 RAS. c s c s c s c s c s c s c s c s 0 l-0 l+1 SV S

The signal of mantle anisotropy in the coupling of normal modes

We investigate whether the coupling of normal mode (NM) multiplets can help us constrain mantle anisotropy. We first derive explicit expressions of the generalized structure coefficients of coupled modes in terms of elastic coefficients, including the Love parameters describing radial anisotropy and the parameters describing azimuthal anisotropy (Jc, Js, Kc, Ks, Mc, Ms, Bc, Bs, Gc, Gs, Ec, Es, Hc, Hs, Dc and Ds). We detail the selection rules that describe which modes can couple together and which elastic parameters govern their coupling. We then focus on modes of type 0Sl-0Tl+1 and determine whether they can be used to constrain mantle anisotropy. We show that they are sensitive to six elastic parameters describing azimuthal anisotropy, in addition to the two shear-wave elastic parameters L and N (i.e. VSV and VSH). We find that neither isotropic nor radially anisotropic mantle models can fully explain the observed degree two signal. We show that the NM signal that remains after correction for the effect of the crust and mantle radial anisotropy can be explained by the presence of azimuthal anisotropy in the upper mantle. Although the data favour locating azimuthal anisotropy below 400km, its depth extent and distribution is still not well constrained by the data. Consideration of NM coupling can thus help constrain azimuthal anisotropy in the mantle, but joint analyses with surface-wave phase velocities is needed to reduce the parameter trade-offs and improve our constraints on the individual elastic parameters and the depth location of the azimuthal anisotropy. © 2008 The Authors Journal compilation © 2008 RAS

Radial anisotropy in seismic reference models of the mantle

Sambridge's Neighborhood Algorithm was applied to normal mode and surface wave phase velocity data to determine the likelihood of radial anisotropy in mantle reference models. This full model space search technique provides probability density functions for each model parameter and therefore reliable estimates of resolution and uncertainty, without having to introduce unnecessary regularization on the model space. Our results for shear wave anisotropy (described by parameter ξ) show a fast decrease with depth with no significant deviation ftom Preliminary Reference Earth Model (PREM) at any depth. The data do not require strong deviations from PREM for P wave anisotropy either, except between 220 and 400 km depth and in the D″layer. The intermediate parameter η might depart from PREM between 220 and 670 km depth. This implies a likely deeper P wave anisotropy and η anisotropy than S wave anisotropy. The sign change in the anisotropic parameters across the 670-km discontinuity found by other authors is not warranted by our data set, which is far more extensive than in previous studies. We found that density needs to be well resolved because we observe a high dependence of the results for P wave-related parameters on the presence or absence of density in the parameterization. S wave anisotropy and η are less affected by density. A well-resolved negative density anomaly was found in the uppermost mantle, and a density excess was observed in the transition zone and the lowermost mantle which might be a seismic signature of the recently identified postperovskite phase. Copyright 2006 by the American Geophysical Union