40 research outputs found
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Genome-wide Integrative Analysis of Zika-Virus-Infected Neuronal Stem Cells Reveals Roles for MicroRNAs in Cell Cycle and Stemness.
Zika virus (ZIKV) infection is implicated in severe fetal developmental disorders, including microcephaly. MicroRNAs (miRNAs) post-transcriptionally regulate numerous processes associated with viral infection and neurodegeneration, but their contribution to ZIKV pathogenesis is unclear. We analyzed the mRNA and miRNA transcriptomes of human neuronal stem cells (hNSCs) during infection with ZIKV MR766 and Paraiba strains. Integration of the miRNA and mRNA expression data into regulatory interaction networks showed that ZIKV infection resulted in miRNA-mediated repression of genes regulating the cell cycle, stem cell maintenance, and neurogenesis. Bioinformatics analysis of Argonaute-bound RNAs in ZIKV-infected hNSCs identified a number of miRNAs with predicted involvement in microcephaly, including miR-124-3p, which dysregulates NSC maintenance through repression of the transferrin receptor (TFRC). Consistent with this, ZIKV infection upregulated miR-124-3p and downregulated TFRC mRNA in ZIKV-infected hNSCs and mouse brain tissue. These data provide insights into the roles of miRNAs in ZIKV pathogenesis, particularly the microcephaly phenotype
Zika virus infection reprograms global transcription of host cells to allow sustained infection.
Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-BarrΓ© syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection. The four cell types differed in their susceptibility to ZIKV infection, consistent with differences in their expression of viral response genes before infection. Clustering and network analyses of genes differentially expressed after ZIKV infection revealed changes related to the adaptive immune system, angiogenesis and host metabolic processes that are conducive to sustained viral production. Genes related to the adaptive immune response were downregulated in microglia cells, suggesting that ZIKV effectively evades the immune response after reaching the central nervous system. Like other viruses, ZIKV diverts host cell resources and reprograms the metabolic machinery to support RNA metabolism, ATP production and glycolysis. Consistent with these transcriptomic analyses, nucleoside metabolic inhibitors abrogated ZIKV replication in microglia cells
Tribological characteristics of pet track etching membranes after dry friction
The article shows the research of dry friction of PET track membrane according to the pin-on-disk scheme. The results had showed that the friction coefficient increased marginally by increasing the duration of the test. The raise of tests speed more than 5 mm/s contributed to the friction coefficient increasing. The friction coefficient values were comparable in the (1,5 - 5) mm/s range. The load increasing contributed to friction coefficient increasing
ΠΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠ½ΡΡ ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² Π±ΠΈΠΎΡΠΎΠ²ΠΌΠ΅ΡΡΠΈΠΌΡΡ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ½ΡΡ ΠΈ ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ²
ΠΠ±ΡΠ΅ΠΊΡΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π»ΡΡΡΡΡ ΠΎΠ±ΡΠ°Π·ΡΡ ΠΏΠΎΠ»ΠΈΠ»Π°ΠΊΡΠΈΠ΄Π° (ΠΠ), Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ°ΠΏΠ°ΡΠΈΡΠ° (ΠΠ) ΠΈ ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡΠΎΠ² Π½Π° ΠΈΡ
ΠΎΡΠ½ΠΎΠ²Π΅ Ρ ΠΌΠ°ΡΡΠΎΠ²ΡΠΌ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² 80/20, 70/30 ΠΈ 60/40 (ΠΠ/ΠΠ) Π² ΠΈΡΡ
ΠΎΠ΄Π½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ ΠΈ ΠΏΠΎΡΠ»Π΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΈΡ
ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ ΠΈΠΎΠ½Π°ΠΌΠΈ ΡΠ΅ΡΠ΅Π±ΡΠ° ΠΈ ΡΠ³Π»Π΅ΡΠΎΠ΄Π° ΠΈ Π°ΡΠΌΠΎΡΡΠ΅ΡΠ½ΠΎΠΉ Π½ΠΈΠ·ΠΊΠΎΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΠΎΠΉ ΠΏΠ»Π°Π·ΠΌΠΎΠΉ.
Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΡΡΠΊΡΡΡΡ, ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΡΠ²ΠΎΠΉΡΡΠ² ΠΈΡΡ
ΠΎΠ΄Π½ΡΡ
ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΏΠΎΠ»ΠΈΠ»Π°ΠΊΡΠΈΠ΄Π° (ΠΠ), Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ°ΠΏΠ°ΡΠΈΡΠ° (ΠΠ) ΠΈ ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡΠΎΠ² Π½Π° ΠΈΡ
ΠΎΡΠ½ΠΎΠ²Π΅ Ρ ΠΌΠ°ΡΡΠΎΠ²ΡΠΌ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² 80/20, 70/30 ΠΈ 60/40 (ΠΠ/ΠΠ) ΠΈ ΠΏΠΎΡΠ»Π΅ ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠ½ΠΎΠΉ ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ.The object of the study is samples of polylactide (PL), hydroxyapatite (HA) and composites based on them with a mass ratio of components 80/20, 70/30 and 60/40 (PL / HA) in the initial state and after their surface modification by silver and carbon ions and atmospheric low-temperature plasma.
Targeted work is the study of the structures, physico-chemical and functional properties of the initial samples of polylactide (PL), hydroxyapatite (HA) and composites based on them with a mass ratio of components 80/20, 70/30 and 60/40 (PL / HA) and after surface ion-plasma modification
The Long Noncoding RNA HEAL Regulates HIV-1 Replication through Epigenetic Regulation of the HIV-1 Promoter.
A major challenge in finding a cure for HIV-1/AIDS is the difficulty in identifying and eradicating persistent reservoirs of replication-competent provirus. Long noncoding RNAs (lncRNAs, >200 nucleotides) are increasingly recognized to play important roles in pathophysiology. Here, we report the first genome-wide expression analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs). We identified an lncRNA, which we named HIV-1-enhanced lncRNA (HEAL), that is upregulated by HIV-1 infection of MDMs, microglia, and T lymphocytes. Peripheral blood mononuclear cells of HIV-1-infected individuals show elevated levels of HEAL Importantly, HEAL is a broad enhancer of multiple HIV-1 strains because depletion of HEAL inhibited X4, R5, and dual-tropic HIV replications and the inhibition was rescued by HEAL overexpression. HEAL forms a complex with the RNA-binding protein FUS, which facilitates HIV replication through at least two mechanisms: (i) HEAL-FUS complex binds the HIV promoter and enhances recruitment of the histone acetyltransferase p300, which positively regulates HIV transcription by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin-dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Notably, HEAL knockdown and knockout mediated by RNA interference (RNAi) and CRISPR-Cas9, respectively, prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment in vitro Our results suggest that silencing of HEAL or perturbation of the HEAL-FUS ribonucleoprotein complex could provide a new epigenetic silencing strategy to eradicate viral reservoirs and effect a cure for HIV-1/AIDS.IMPORTANCE Despite our increased understanding of the functions of lncRNAs, their potential to develop HIV/AIDS cure strategies remains unexplored. A genome-wide analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs) was performed, and 1,145 differentially expressed lncRNAs were identified. An lncRNA named HIV-1-enhanced lncRNA (HEAL) is upregulated by HIV-1 infection and promotes HIV replication in T cells and macrophages. HEAL forms a complex with the RNA-binding protein FUS to enhance transcriptional coactivator p300 recruitment to the HIV promoter. Furthermore, HEAL knockdown and knockout prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment, suggesting HEAL as a potential therapeutic target to cure HIV-1/AIDS
Formation of budget revenues of different levels coming from a region
The issue about the ability of the Russian Federation territories to accumulate revenues coming to different levels of the country's budget system is actual. The study analyzes the tax revenues arriving from the Tomsk region to different units of the budget system over a 3-year period, moreover, the industry specifics of the region is revealed. Author also pays attention to the problem of tax deduction large share credited to the federal budget that is a consequence of the fiscal policy of the federal center. Moreover, the paper considers the implementation of the planned appointments, the structure, as well as the dynamics of the revenue receipts of the Tomsk region consolidated budget