Quantifying Microstructural Evolution in Moving Magma

Many of the grand challenges in volcanic and magmatic research are focused on understanding the dynamics of highly heterogeneous systems and the critical conditions that enable magmas to move or eruptions to initiate. From the formation and development of magma reservoirs, through propagation and arrest of magma, to the conditions in the conduit, gas escape, eruption dynamics, and beyond into the environmental impacts of that eruption, we are trying to define how processes occur, their rates and timings, and their causes and consequences. However, we are usually unable to observe the processes directly. Here we give a short synopsis of the new capabilities and highlight the potential insights that in situ observation can provide. We present the XRheo and Pele furnace experimental apparatus and analytical toolkit for the in situ X-ray tomography-based quantification of magmatic microstructural evolution during rheological testing. We present the first 3D data showing the evolving textural heterogeneity within a shearing magma, highlighting the dynamic changes to microstructure that occur from the initiation of shear, and the variability of the microstructural response to that shear as deformation progresses. The particular shear experiments highlighted here focus on the effect of shear on bubble coalescence with a view to shedding light on both magma transport and fragmentation processes. The XRheo system is intended to help us understand the microstructural controls on the complex and non-Newtonian evolution of magma rheology, and is therefore used to elucidate the many mobilization, transport, and eruption phenomena controlled by the rheological evolution of a multi-phase magmatic flows. The detailed, in situ characterization of sample textures presented here therefore represents the opening of a new field for the accurate parameterization of dynamic microstructural control on rheological behavior

Dynamic, Large-Scale Profiling of Transcription Factor Activity from Live Cells in 3D Culture

phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture.TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A.This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a platform for screening therapeutics

Phosphorylation of p65(RelA) on Ser547 by ATM Represses NF-κB-Dependent Transcription of Specific Genes after Genotoxic Stress

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65

Inhibition of Interferon Induction and Action by the Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus

The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus). We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons. Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU) found in the viral RNA polymerase. Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action. Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU

Euclid preparation XLVIII. The pre-launch Science Ground Segment simulation framework

Context. The European Space Agency’s Euclid mission is one of a raft of forthcoming large-scale cosmology surveys that will map the large-scale structure in the Universe with unprecedented precision. The mission will collect a vast amount of data that will be processed and analysed by Euclid’s Science Ground Segment (SGS). The development and validation of the SGS pipeline requires state-of-the-art simulations with a high level of complexity and accuracy that include subtle instrumental features not accounted for previously as well as faster algorithms for the large-scale production of the expected Euclid data products. // Aims. In this paper, we present the Euclid SGS simulation framework as it is applied in a large-scale end-to-end simulation exercise named Science Challenge 8. Our simulation pipeline enables the swift production of detailed image simulations for the construction and validation of the Euclid mission during its qualification phase and will serve as a reference throughout operations. // Methods. Our end-to-end simulation framework started with the production of a large cosmological N-body simulation that we used to construct a realistic galaxy mock catalogue. We performed a selection of galaxies down to IE=26 and 28 mag, respectively, for a Euclid Wide Survey spanning 165 deg2 and a 1 deg2 Euclid Deep Survey. We built realistic stellar density catalogues containing Milky Way-like stars down to H < 26 from a combination of a stellar population synthesis model of the Galaxy and real bright stars. Using the latest instrumental models for both the Euclid instruments and spacecraft as well as Euclid-like observing sequences, we emulated with high fidelity Euclid satellite imaging throughout the mission’s lifetime. // Results. We present the SC8 dataset, consisting of overlapping visible and near-infrared Euclid Wide Survey and Euclid Deep Survey imaging and low-resolution spectroscopy along with ground-based data in five optical bands. This extensive dataset enables end-to-end testing of the entire ground segment data reduction and science analysis pipeline as well as the Euclid mission infrastructure, paving the way for future scientific and technical developments and enhancements

XXXIV. The effect of linear redshift-space distortions in photometric galaxy clustering and its cross-correlation with cosmic shear

CONTEXT: The cosmological surveys that are planned for the current decade will provide us with unparalleled observations of the distribution of galaxies on cosmic scales, by means of which we can probe the underlying large-scale structure (LSS) of the Universe. This will allow us to test the concordance cosmological model and its extensions. However, precision pushes us to high levels of accuracy in the theoretical modelling of the LSS observables, so that no biases are introduced into the estimation of the cosmological parameters. In particular, effects such as redshift-space distortions (RSD) can become relevant in the computation of harmonic-space power spectra even for the clustering of the photometrically selected galaxies, as has previously been shown in literature. AIMS: In this work, we investigate the contribution of linear RSD, as formulated in the Limber approximation by a previous work, in forecast cosmological analyses with the photometric galaxy sample of the Euclid survey. We aim to assess their impact and to quantify the bias on the measurement of cosmological parameters that would be caused if this effect were neglected. METHODS: We performed this task by producing mock power spectra for photometric galaxy clustering and weak lensing, as is expected to be obtained from the Euclid survey. We then used a Markov chain Monte Carlo approach to obtain the posterior distributions of cosmological parameters from these simulated observations. RESULTS: When the linear RSD is neglected, significant biases are caused when galaxy correlations are used alone and when they are combined with cosmic shear in the so-called 3 × 2 pt approach. These biases can be equivalent to as much as 5σ when an underlying ΛCDM cosmology is assumed. When the cosmological model is extended to include the equation-of-state parameters of dark energy, the extension parameters can be shifted by more than 1σ

The effects of mutant Ras proteins on the cell signalome

The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells. © 2020, The Author(s)

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

Euclid preparation XXXV. Covariance model validation for the two-point correlation function of galaxy clusters

Aims. We validate a semi-analytical model for the covariance of the real-space two-point correlation function of galaxy clusters. // Methods. Using 1000 PINOCCHIO light cones mimicking the expected Euclid sample of galaxy clusters, we calibrated a simple model to accurately describe the clustering covariance. Then, we used this model to quantify the likelihood-analysis response to variations in the covariance, and we investigated the impact of a cosmology-dependent matrix at the level of statistics expected for the Euclid survey of galaxy clusters. // Results. We find that a Gaussian model with Poissonian shot-noise does not correctly predict the covariance of the two-point correlation function of galaxy clusters. By introducing a few additional parameters fitted from simulations, the proposed model reproduces the numerical covariance with an accuracy of 10%, with differences of about 5% on the figure of merit of the cosmological parameters Ωm and σ8. We also find that the covariance contains additional valuable information that is not present in the mean value, and the constraining power of cluster clustering can improve significantly when its cosmology dependence is accounted for. Finally, we find that the cosmological figure of merit can be further improved when mass binning is taken into account. Our results have significant implications for the derivation of cosmological constraints from the two-point clustering statistics of the Euclid survey of galaxy clusters