Multiple transition zone seismic discontinuities and low velocity layers below western United States

With P-to-S converted waves recorded at seismic stations of the U.S. Transportable Array, we image the fine structure of upper mantle and transition zone (TZ) beneath the western U.S. We map the topographies of seismic discontinuities by stacking data by common conversion points along profiles. Systematic depth and amplitude measurements are performed not only for the well-known “410” and “660” interfaces but also for minor seismic discontinuities identified around 350, 590, and 630 km depths. The amplitude of conversion suggests shear wave velocity (Vs) increase by 4% at the 410 and the 660. The observed 660 velocity contrast is smaller than expected from the 6% in IASP91 but consistent with a pyrolitic model of mantle composition. The Gorda plate, subducted under northern California, is tracked to the TZ where it seems to flatten and induce uplift of the 410 under northern Nevada. Maps of 410/660 amplitude/topography reveal that the TZ is anomalous beneath the geographical borders of Washington, Oregon, and Idaho, with (1) a thickened TZ, (2) a sharp change in depth of the 660, (3) a reduced 410 conversion amplitude in the North, and (4) a positive “630” discontinuity. Such anomalous structure might be inherited from the past history of plate subduction/accretion. A thinned TZ under the Yellowstone suggests higher-than-average temperatures, perhaps due to a deep thermal plume. Both the “350” and the “590” negative discontinuities extend over very large areas. They might be related either to an increased water content in the TZ, a significant amount of oceanic material accumulated through the past 100 Myr, or both.National Science Foundation (U.S.) (VICI grant NWO:VICI865.03.007

Evidence of Volatile-Induced Melting in the Northeast Asian Upper Mantle

A seismic low velocity layer (LVL) above the mantle transition zone (MTZ), often thought to be caused by volatile-induced melting, can significantly modulate planetary volatile cycles. In this work, we show that an LVL observed beneath northeast Asia is characterized by small, 0.8 (Formula presented.) 0.5 vol%, average degrees of partial melting. Seismically derived P-T conditions of the LVL indicate that slab-derived (Formula presented.), possibly combined with small amounts of (Formula presented.) O, is necessary to induce melting. Modeling the reactive infiltration instability of the melt in a stationary mantle above a stalled slab, we demonstrate that the volatile-rich melt slowly rises above the stalled slab in the MTZ, with percolation velocities of 200–500 (Formula presented.) m/yr. The melt remains stable within the LVL for this geologically significant period of time, potentially transferring up to 52 Mt/yr of (Formula presented.) from the subducting slab to the mantle for an LVL similar in areal extent ((Formula presented.)) to the northeast Asian LVL. Reaction between the melt channels and the LVL mantle precipitates up to 200 ppmw solid C in localized zones. Using the inferred small melt volume fraction to model trace element abundances and isotopic signatures, we show that interaction between this melt and the surrounding mantle can over the long-term produce rocks bearing a HIMU like geochemical signature

Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination.

The Omicron BQ.1.1 variant is now the major SARS-CoV-2 circulating strain in many countries. Because of the many mutations present in its Spike glycoprotein, this variant is resistant to humoral responses elicited by monovalent mRNA vaccines. With the goal to improve immune responses against Omicron subvariants, bivalent mRNA vaccines have recently been approved in several countries. In this study, we measure the capacity of plasma from vaccinated individuals, before and after a fourth dose of mono- or bivalent mRNA vaccine, to recognize and neutralize the ancestral (D614G) and the BQ.1.1 Spikes. Before and after the fourth dose, we observe a significantly better recognition and neutralization of the ancestral Spike. We also observe that fourth-dose vaccinated individuals who have been recently infected better recognize and neutralize the BQ.1.1 Spike, independently of the mRNA vaccine used, than donors who have never been infected or have an older infection. Our study supports that hybrid immunity, generated by vaccination and a recent infection, induces higher humoral responses than vaccination alone, independently of the mRNA vaccine used

Stochastic Inversion of P-to-S Converted Waves for Mantle Composition and Thermal Structure: Methodology and Application

We present a new methodology for inverting P‐to‐S receiver function (RF) waveforms directly for mantle temperature and composition. This is achieved by interfacing the geophysical inversion with self‐consistent mineral phase equilibria calculations from which rock mineralogy and its elastic properties are predicted as a function of pressure, temperature, and bulk composition. This approach anchors temperatures, composition, seismic properties, and discontinuities that are in mineral physics data, while permitting the simultaneous use of geophysical inverse methods to optimize models of seismic properties to match RF waveforms. Resultant estimates of transition zone (TZ) topography and volumetric seismic velocities are independent of tomographic models usually required for correcting for upper mantle structure. We considered two end‐member compositional models: the equilibrated equilibrium assemblage (EA) and the disequilibrated mechanical mixture (MM) models. Thermal variations were found to influence arrival times of computed RF waveforms, whereas compositional variations affected amplitudes of waves converted at the TZ discontinuities. The robustness of the inversion strategy was tested by performing a set of synthetic inversions in which crustal structure was assumed both fixed and variable. These tests indicate that unaccounted‐for crustal structure strongly affects the retrieval of mantle properties, calling for a two‐step strategy presented herein to simultaneously recover both crustal and mantle parameters. As a proof of concept, the methodology is applied to data from two stations located in the Siberian and East European continental platforms.This work was supported by a grant from the Swiss National Science Foundation (SNF project 200021_159907). B. T. was funded by a Délégation CNRS and Congé pour Recherches et Conversion Thématique from the Université de Lyon to visit the Research School of Earth Sciences (RSES), The Australian National University (ANU). B. T. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 79382

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD(+)-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD(+)-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.Peer reviewe

INTEGRAL/SPI ground calibration

Three calibration campaigns of the spectrometer SPI have been performed before launch in order to determine the instrument characteristics, such as the effective detection area, the spectral resolution and the angular resolution. Absolute determination of the effective area has been obtained from simulations and measurements. At 1 MeV, the effective area is 65 cm^2 for a point source on the optical axis, the spectral resolution ~2.3 keV. The angular resolution is better than 2.5 deg and the source separation capability about 1 deg. Some temperature dependant parameters will require permanent in-flight calibration.Comment: 9 pages, 12 figures, 2 tables. Accepted for publication in A&AL (INTEGRAL Special issue

Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration

Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells

Continental flood basalts derived from the hydrous mantle transition zone

It has previously been postulated that the Earth's hydrous mantle transition zone may play a key role in intraplate magmatism, but no confirmatory evidence has been reported. Here we demonstrate that hydrothermally altered subducted oceanic crust was involved in generating the late Cenozoic Chifeng continental flood basalts of East Asia. This study combines oxygen isotopes with conventional geochemistry to provide evidence for an origin in the hydrous mantle transition zone. These observations lead us to propose an alternative thermochemical model, whereby slab-triggered wet upwelling produces large volumes of melt that may rise from the hydrous mantle transition zone. This model explains the lack of pre-magmatic lithospheric extension or a hotspot track and also the arc-like signatures observed in some large-scale intracontinental magmas. Deep-Earth water cycling, linked to cold subduction, slab stagnation, wet mantle upwelling and assembly/breakup of supercontinents, can potentially account for the chemical diversity of many continental flood basalts

Targeting N-myristoylation for therapy of B-cell lymphomas

N-myristoyltransferases (NMTs) target many signaling proteins to membranes. Here the authors show an NMT inhibitor named PCLX-001 selectively kills lymphoma cells by shutting down their main survival signaling pathway and offers an additional treatment strategy for lymphoma patients