Plausible Constraints on the Range of Bulk Terrestrial Exoplanet Compositions in the Solar Neighborhood

Rocky planet compositions regulate planetary evolution by affecting core sizes, mantle properties, and melting behaviors. Yet, quantitative treatments of this aspect of exoplanet studies remain generally underexplored. We attempt to constrain the range of potential bulk terrestrial exoplanet compositions in the solar neighborhood (<200 pc). We circumscribe probable rocky exoplanet compositions based on a population analysis of stellar chemical abundances from the Hypatia and GALAH catalogs. We apply a devolatilization model to simulate compositions of hypothetical, terrestrial-type exoplanets in the habitable zones around Sun-like stars, considering elements O, S, Na, Si, Mg, Fe, Ni, Ca, and Al. We further apply core-mantle differentiation by assuming constant oxygen fugacity, and model the consequent mantle mineralogy with a Gibbs energy minimization algorithm. We report statistics on several compositional parameters and propose a reference set of (21) representative planet compositions for use as end-member compositions in imminent modeling and experimental studies. We find a strong correlation between stellar Fe/Mg and metallic-core sizes, which can vary from 18 to 35 wt%. Furthermore, stellar Mg/Si gives a first-order indication of mantle mineralogy, with high-Mg/Si stars leading to weaker, ferropericlase-rich mantles, and low-Mg/Si stars leading to mechanically stronger mantles. The element Na, which modulates crustal buoyancy and mantle clinopyroxene fraction, is affected by devolatilization the most. While we find that planetary mantles mostly consist of Fe/Mg silicates, the core sizes and relative abundances of common minerals can nevertheless vary significantly among exoplanets. These differences likely lead to different evolutionary pathways among rocky exoplanets in the solar neighborhood

Guidelines for measuring and reporting environmental parameters for experiments in greenhouses

Background: The importance of appropriate, accurate measurement and reporting of environmental parameters in plant sciences is a significant aspect of quality assurance for all researchers and their research. There is a clear need for ensuring research across the world can be compared, understood and where necessary replicated by fellow researchers. A common set of guidelines to educate, assist and encourage comparativeness is of great importance. On the other hand, the level of effort and attention to detail by an individual researcher should be commensurate with the particular research being conducted. For example, a researcher focusing on interactions of light and temperature should measure all relevant parameters and report a measurement summary that includes sufficient detail allowing for replication. Such detail may be less relevant when the impact of environmental parameters on plant growth and development is not the main research focus. However, it should be noted that the environmental experience of a plant during production can have significant impact when subsequent experiments investigate plants at a molecular, biochemical or genetic level or where species interactions are considered. Thus, researchers are encouraged to make a critical assessment of what parameters are of primary importance in their research and these parameters should be measured and reported. Content: This paper brings together a collection of parameters that the authors, as members of International Committee on Controlled Environment Guidelines (ICCEG) in consultation with members of our three parent organizations, believe constitute those which should be recorded and reported when publishing scientific data from experiments in greenhouses. It provides recommendations to end users on when, how and where these parameters should be measured along with the appropriate internationally standardized units that should be used

The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells

CLL cell trafficking between blood and tissue compartments is an integral part of the disease process. Idelalisib, a phosphoinositide 3-kinase delta (PI3K\u3b4) inhibitor causes rapid lymph node shrinkage, along with an increase in lymphocytosis, prior to inducing objective responses in CLL patients. This characteristic activity presumably is due to CLL cell redistribution from tissues into the blood, but the underlying mechanisms are not fully understood. We therefore analyzed idelalisib effects on CLL cell adhesion to endothelial and bone marrow stromal cells (EC, BMSC). We found that idelalisib inhibited CLL cell adhesion to EC and BMSC under static and shear flow conditions. TNF\u3b1-induced VCAM-1 (CD106) expression in supporting layers increased CLL cell adhesion and accentuated the inhibitory effect of idelalisib. Co-culture with EC and BMSC also protected CLL from undergoing apoptosis, and this EC- and BMSC-mediated protection was antagonized by idelalisib. Furthermore, we demonstrate that CLL cell adhesion to EC and VLA-4 (CD49d) resulted in the phosphorylation of Akt, which was sensitive to inhibition by idelalisib. These findings demonstrate that idelalisib interferes with integrin-mediated CLL cell adhesion to EC and BMSC, providing a novel mechanism to explain idelalisib-induced redistribution of CLL cells from tissues into the blood

Transcriptional Silencing of the Wnt-Antagonist DKK1 by Promoter Methylation Is Associated with Enhanced Wnt Signaling in Advanced Multiple Myeloma

The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling

PI3K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia (CLL).

B cells provide immunity to extracellular pathogens by secreting a diverse repertoire of antibodies with high affinity and specificity for exposed antigens. The B cell receptor (BCR) is a transmembrane antibody, which facilitates the clonal selection of B cells producing secreted antibodies of the same specificity. The diverse antibody repertoire is generated by V(D)J recombination of heavy and light chain genes, whereas affinity maturation is mediated by activation-induced cytidine deaminase (AID)-mediated mutagenesis. These processes, which are essential for the generation of adaptive humoral immunity, also render B cells susceptible to chromosomal rearrangements and point mutations that in some cases lead to cancer. In this chapter, we will review the central role of PI3K s in mediating signals from the B cell receptor that not only facilitate the development of functional B cell repertoire, but also support the growth and survival of neoplastic B cells, focusing on chronic lymphocytic leukemia (CLL) B cells. Perhaps because of the central role played by PI3K in BCR signaling, B cell leukemia and lymphomas are the first diseases for which a PI3K inhibitor has been approved for clinical use

Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation

To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation