Micro-Raman study of crichtonite group minerals enclosed into mantle garnet

We report the first comprehensive micro-Raman study of crichtonite group minerals (CGM) as inclusions in pyropic garnet grains from peridotite and pyroxenite mantle xenoliths of the Yakutian kimberlites as well as in garnet xenocrysts from the Aldan shield lamprophyres (Russia). The CGM form (i) morphologically oriented needles, lamellae, and short prisms and (ii) optically unoriented subhedral to euhedral grains, either single or intergrown with other minerals. We considered common mantle-derived CGM species (like loveringite, lindsleyite, and their analogues), with Ca, Ba, or Sr dominating in the dodecahedral A site and Zr or Fe in the octahedral B site. The Raman bands at the region of 600–830 cm−1 are indicative of CGM and their crystal-chemical distinction, although the intensity and shape of the bands appear to be dependent on laser beam power and wavelength. The factor-group analysis based on the loveringite crystal structure showed the octahedral and tetrahedral cation groups with 18f and 6c Wyckoff positions, namely, dominantly TiO6 and to a lower extent CrO6, MgO4, and FeO4 groups, to be the major contributors to the Raman spectral features. The ionic groups with dodecahedral (M0) and octahedral (M1) coordination are inactive for Raman scattering while active in infrared absorption. A number of observed Raman modes in the CGM spectra are several times lower than that predicted by the factor group analysis. The noticed broadening of modes in the CGM Raman spectra may result from a combining of bands at the narrow frequency shift regions. Solid solution behavior, luminescence, and partial metamictization of the CGM may exert additional influence on the Raman band shape. The Raman spectral features showed CGM to be accurately identified and distinguished from other Ti-, Fe-, Cr-, and Zr-containing oxides (e.g., ilmenite or those of spinel and magnetoplumbite groups) occurring as accessory mantle minerals. © 2020 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons LtdRussian Science Foundation, RSF: 18‐77‐10062Council on grants of the President of the Russian FederationThis study was supported by the Russian Science Foundation (Grant 18‐77‐10062). The equipment of the Ural Center for Shared Use «Modern Nanotechnology», Ural Federal University, and the Analytical Center for Multi‐elemental and Isotope Research, IGM, was used. Sampling was supported by the Russian Federation state assignment project of IGM. We are grateful to Nikolai V. Sobolev for Samples O‐173, O‐39, and O‐264. Vladimir N. Korolyuk, Elena N. Nigmatulina (IGM), and Allan Patchen (UT) are highly appreciated for the help with EMP analyses. We express our sincere thanks to F. Nestola and an anonymous reviewer for their thorough reviews and helpful suggestions, and to C. Marshall for regardful editorial handling of the manuscript on every stage of its revision

Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer

Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series

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

Epigenetics and the estrogen receptor

The position effect variegation in Drosophila and Schizosaccharomyces pombe, and higher-order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group, (e.g., histone deacetylases ([HDACs]), protein phosphatases) and enhancer E(Var) group (e.g., ATP [adenosine 5\u27-triphosphate]-dependent nucleosome remodeling proteins). Higher-order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin, and histone tails in turn serve as platforms for recruitment of signaling modules that include nonhistone proteins such as heterochromatin protein (HP1) and NuRD. Because the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also target nonhistone substrates, a mechanism is in place by which epigenetic regulatory processes can affect the function of these alternate substrates. The posttranslational modification of histones, through phosphorylation and acetylation at specific residues, alters chromatin structure in an orchestrated manner in response to specific signals and is considered the basis of a histone code. In an analogous manner, specific residues within transcription factors form a signaling module within the transcription factor to determine genetic target specificity and cellular fate. The architecture of these signaling cascades in transcription factors (SCITs) are poorly understood. The regulation of estrogen receptor (ERalpha) by enzymes that convey epigenetic signals is carefully orchestrated and is reviewed here

Monosodium urate crystals promote innate anti-mycobacterial immunity and improve BCG efficacy as a vaccine against tuberculosis

A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination

Oxidative stress in pregnancy and fertility pathologies

Oxidative stress designates the state of imbalance between reactive oxygen species (ROS) production and antioxidant levels. In a healthy placenta, there is an increase in ROS production, due to formation of new tissues and inherent metabolism, but this is balanced by higher levels of antioxidants. However, this balance is lost in some situations, with a consequent increase in oxidative stress levels. Oxidative stress has been implicated in several placental disorders and pregnancy pathologies. The present review intends to summarize what is known about the relationship between oxidative stress and well-known pregnancy disorders

Small Non-coding RNAs Govern Mammary Gland Tumorigenesis

Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described

Biogenesis and Dynamics of Mitochondria during the Cell Cycle: Significance of 3′UTRs

Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of β-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (ΔΨm) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of β-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 3′UTR of the transcript. The 3′UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated β-F1-ATPase expression in human cancer

Maps of Open Chromatin Guide the Functional Follow-Up of Genome-Wide Association Signals: Application to Hematological Traits

Turning genetic discoveries identified in genome-wide association (GWA) studies into biological mechanisms is an important challenge in human genetics. Many GWA signals map outside exons, suggesting that the associated variants may lie within regulatory regions. We applied the formaldehyde-assisted isolation of regulatory elements (FAIRE) method in a megakaryocytic and an erythroblastoid cell line to map active regulatory elements at known loci associated with hematological quantitative traits, coronary artery disease, and myocardial infarction. We showed that the two cell types exhibit distinct patterns of open chromatin and that cell-specific open chromatin can guide the finding of functional variants. We identified an open chromatin region at chromosome 7q22.3 in megakaryocytes but not erythroblasts, which harbors the common non-coding sequence variant rs342293 known to be associated with platelet volume and function. Resequencing of this open chromatin region in 643 individuals provided strong evidence that rs342293 is the only putative causative variant in this region. We demonstrated that the C- and G-alleles differentially bind the transcription factor EVI1 affecting PIK3CG gene expression in platelets and macrophages. A protein–protein interaction network including up- and down-regulated genes in Pik3cg knockout mice indicated that PIK3CG is associated with gene pathways with an established role in platelet membrane biogenesis and thrombus formation. Thus, rs342293 is the functional common variant at this locus; to the best of our knowledge this is the first such variant to be elucidated among the known platelet quantitative trait loci (QTLs). Our data suggested a molecular mechanism by which a non-coding GWA index SNP modulates platelet phenotype