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"Petrova, Evgeniya"
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Comparison of bulk interior and fusion crust of Chelyabinsk LL5, Ozerki L6 and Kemer L4 ordinary chondrite fragments using X-ray diffraction and Mössbauer spectroscopy
Fragments of Chelyabinsk LL5 No 1a and 2a, Kemer L4 and Ozerki L6 ordinary chondrites covered with the fusion crust were studied by X-ray diffraction (XRD) and Mössbauer spectroscopy. In addition, Kemer L4 and Ozerki L6 were studied by magnetization measurements. These results were analyzed for comparison of the bulk interior and the fusion crust in these meteorites. XRD showed the main and minor iron-bearing phases variations between both the bulk interior and the fusion crust in these meteorite fragments. Magnetization measurements of the bulk interior showed the magnetic phase transitions in chromite and hercynite in Ozerki L6 and Kemer L4 and different saturation magnetization moments for two meteorites as well as its decrease for the fusion crust from both fragments. Mössbauer spectra of the bulk interior and the fusion crust from Chelyabinsk LL5 No 1a and 2a, Kemer L4 and Ozerki L6 showed some differences in the numbers and contents of iron-bearing phases, small variations in the 57Fe hyperfine parameters in the same iron-bearing phases from different ordinary chondrites. Some differences in the Fe2+ occupations of the M1 and M2 sites in silicate crystals as well as variations in the temperatures of cation equilibrium distribution between these sites in olivine and orthopyroxene in the bulk interior were determined based on XRD and Mössbauer data.
Journal Article
Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen
Flaviviruses, such as dengue (DENV), West Nile (WNV), yellow fever (YFV) and Zika (ZIKV) viruses, are mosquito-borne pathogens that present a major risk to global public health. To identify host factors that promote flavivirus replication, we performed a genome-wide gain-of-function cDNA screen for human genes that enhance the replication of flavivirus reporter particles in human cells. The screen recovered seventeen potential host proteins that promote viral replication, including the previously known dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit (DDOST). Using silencing approaches, we validated the role of four candidates in YFV and WNV replication: ribosomal protein L19 (RPL19), ribosomal protein S3 (RPS3), DDOST and importin 9 (IPO9). Applying a panel of virological, biochemical and microscopic methods, we validated further the role of RPL19 and DDOST as host factors required for optimal replication of YFV, WNV and ZIKV. The genome-wide gain-of-function screen is thus a valid approach to advance our understanding of flavivirus replication.
Journal Article
Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways
Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (
SPINK5
) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here we describe a novel and viable,
Spink5
conditional knock-out (cKO) mouse model, allowing to study NS progression. By combining transcriptomics and proteomics, we determine a disease molecular profile common to mouse models and NS patients.
Spink5
cKO mice and NS patients share skin barrier and inflammation signatures defined by up-regulation and increased activity of proteases, IL-17, IL-36, and IL-20 family cytokine signaling. Systemic inflammation in
Spink5
cKO mice correlates with disease severity and is associated with thymic atrophy and enlargement of lymph nodes and spleen. This systemic inflammation phenotype is marked by neutrophils and IL-17/IL-22 signaling, does not involve primary T cell immunodeficiency and is independent of bacterial infection. By comparing skin transcriptomes and proteomes, we uncover several putative substrates of tissue kallikrein-related proteases (KLKs), demonstrating that KLKs can proteolytically regulate IL-36 pro-inflammatory cytokines. Our study thus provides a conserved molecular framework for NS and reveals a KLK/IL-36 signaling axis, adding new insights into the disease mechanisms and therapeutic targets.
Combined transcriptomics and proteomics of skin and lymphoid organs reveal the significance of SPINK5 in the regulation of protease activity and systemic inflammation, providing a conserved molecular framework for Netherton syndrome.
Journal Article
X-ray diffraction and Mössbauer spectroscopy of Gandom Beryan 008 ordinary chondrite
The results of the study of newly found Gandom Beryan 008 H5 ordinary chondrite by means of X-ray diffraction and Mössbauer spectroscopy with additional characterization by optical and scanning electron microscopy are considered. The main iron-bearing phases and their hyperfine parameters were determined. A comparison of Fe2+ occupancies of the M1 and M2 sites in olivine and orthopyroxene determined by X-ray diffraction and Mössbauer spectroscopy data demonstrates some consistency and partial oxidation of Fe2+ in olivine.
Journal Article
Flower-deficient mice have reduced susceptibility to skin papilloma formation
Skin papillomas arise as a result of clonal expansion of mutant cells. It has been proposed that the expansion of pretumoral cell clones is propelled not only by the increased proliferation capacity of mutant cells, but also by active cell selection. Previous studies in Drosophila describe a clonal selection process mediated by the Flower (Fwe) protein, whereby cells that express certain Fwe isoforms are recognized and forced to undergo apoptosis. It was further shown that knock down of fwe expression in Drosophila can prevent the clonal expansion of dMyc-overexpressing pretumoral cells. Here, we study the function of the single predicted mouse homolog of Drosophila Fwe, referred to as mFwe, by clonal overexpression of mFwe isoforms in Drosophila and by analyzing mFwe knock-out mice. We show that clonal overexpression of certain mFwe isoforms in Drosophila also triggers non-autonomous cell death, suggesting that Fwe function is evolutionarily conserved. Although mFwe-deficient mice display a normal phenotype, they develop a significantly lower number of skin papillomas upon exposure to DMBA/TPA two-stage skin carcinogenesis than do treated wild-type and mFwe heterozygous mice. Furthermore, mFwe expression is higher in papillomas and the papilloma-surrounding skin of treated wild-type mice compared with the skin of untreated wild-type mice. Thus, we propose that skin papilloma cells take advantage of Fwe activity to facilitate their clonal expansion.
Journal Article
Assessment of contamination of marine sediments and their potential toxicity in the Uglovoy Bay, Peter the Great Gulf, Sea of Japan/East Sea
The content of harmful heavy metals in the bottom sediments of the Uglovoy Bay (Peter the Great Gulf, Sea of Japan/East Sea) was studied based on the surveys carried out in 2016–2021. The contamination of the sediments in the bay was compared to the background concentrations of elements and to common contamination indices. The degree of contamination was calculated using the contamination factor (
C
f
), modified overall degree of contamination (
mC
d
), and index of geoaccumulation (
I
geo
). The toxicity of marine sediment samples for each metal was evaluated using the threshold effect level/probable effect level (TEL/PEL) values and the sediment quality guideline quotient (SQG-Q). The sources of pollutants entering the studied water area were analyzed. It is shown that the contamination of the Uglovoy Bay occurs continuously as a result of economic activities on its coast. The dynamics of contamination of the bay for the period 2016–2021 is presented.
Journal Article
The sialyl-glycolipid stage-specific embryonic antigen 4 marks a subpopulation of chemotherapy-resistant breast cancer cells with mesenchymal features
Introduction
Chemotherapy resistance resulting in incomplete pathologic response is associated with high risk of metastasis and early relapse in breast cancer. The aim of this study was to identify and evaluate biomarkers of treatment-resistant tumor cells.
Methods
We performed a cell surface marker screen in triple-negative breast cancer patient-derived xenograft models treated with standard care genotoxic chemotherapy. Global expression profiling was used to further characterize the identified treatment-resistant subpopulations.
Results
High expression of sialyl-glycolipid stage-specific embryonic antigen 4 (SSEA4) was found in residual tumor cells surviving chemotherapy and in samples from metastatic patients who relapsed after neoadjuvant chemotherapy. Gene and microRNA (miRNA) expression profiling linked SSEA4 positivity with a mesenchymal phenotype and a deregulation of drug resistance pathways. Functional assays demonstrated a direct link between epithelial–mesenchymal transition (EMT) and SSEA4 expression. Interestingly, SSEA4 expression, EMT, and drug resistance seemed to be regulated posttranscriptionally. Finally, high expression of CMP-
N
-acetylneuraminate-β-galactosamide-α-2,3-sialyltransferase 2 (ST3GAL2), the rate-limiting enzyme of SSEA4 synthesis, was found to be associated with poor clinical outcome in breast and ovarian cancer patients treated with chemotherapy.
Conclusions
In this study, we identified SSEA4 as highly expressed in a subpopulation of tumor cells resistant to multiple commonly used chemotherapy drugs, as well as ST3GAL2, the rate-limiting enzyme of SSEA4 synthesis, as a predictive marker of poor outcome for breast and ovarian cancer patients undergoing chemotherapy. Both biomarkers and additionally identified regulatory miRNAs may be used to further understand chemoresistance, to stratify patient groups in order to avoid ineffective and painful therapies, and to develop alternative treatment regimens for breast cancer patients.
Journal Article
POST-PEASANTRY RUSSIA
The events of the Russian Revolution had a major impact on significant processes in many countries around the world. The Soviet phenomenon is of interest for studying different disciplinary fields and directions. The understanding of post-Soviet Russia is closely related to historical roots.
In this chapter, we propose to pay attention to those phenomena that characterise modern Russia, but have a close relationship with the historical context. We are trying to track connections between Pre-revolutionary Russia, the Soviet Era, and contemporary Russia. The main angle of our research is beyond the Russian Revolution. The historical context is pivotal to an
Book Chapter
