Publications by authors named "Maxim Frolov"

Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by the drug RU486 has gained widespread use in the Drosophila community. However, some concerns were raised as negative effects were seen depending on the stock, transgene, stage, and tissue under study.

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The retinoblastoma (RB) and Hippo pathways interact to regulate cell proliferation and differentiation. However, the mechanism of interaction is not fully understood. Drosophila photoreceptors with inactivated RB and Hippo pathways specify normally but fail to maintain their neuronal identity and dedifferentiate.

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  • Inflammatory epidermolysis bullosa acquisita (EBA) is an autoimmune condition where antibodies against type VII collagen lead to skin inflammation and blistering, mimicked in animal models.
  • Scientists used single-cell RNA sequencing on blood and skin samples to analyze neutrophils, finding significant differences between neutrophils in circulation and those in affected skin.
  • Despite the upregulation of certain genes in activated neutrophils, experiments showed that these genes do not play a crucial role in the disease process of EBA, suggesting their presence might not be necessary for its development.
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The RB and Hippo pathways interact to regulate cell proliferation and differentiation. However, their mechanism of interaction is not fully understood. photoreceptors with inactivated RB and Hippo pathways specify normally but fail to maintain neuronal identity and dedifferentiate.

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The canonical role of the transcription factor E2F is to control the expression of cell cycle genes by binding to the E2F sites in their promoters. However, the list of putative E2F target genes is extensive and includes many metabolic genes, yet the significance of E2F in controlling the expression of these genes remains largely unknown. Here, we used the CRISPR/Cas9 technology to introduce point mutations in the E2F sites upstream of five endogenous metabolic genes in .

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  • The AIDS autoimmune hypothesis suggests that managing autoimmunity against CD4 T lymphocytes could improve HIV infection outcomes.
  • The study explores using neonatal immunization with gp120 to prevent the harmful autoimmune response against CD4 lymphocytes initiated by HIV-1.
  • Results from both computer modeling and experimental studies indicate that neonatal immunization can suppress the production of anti-CD4 autoantibodies, promoting tolerance to CD4 and preventing autoimmune issues in adult rats triggered by gp120.
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Unlabelled: The transcription factor Forkhead box M1 (FoxM1) is overexpressed in breast cancers and correlates with poor prognosis. Mechanistically, FoxM1 associates with CBP to activate transcription and with Rb to repress transcription. Although the activating function of FoxM1 in breast cancer has been well documented, the significance of its repressive activity is poorly understood.

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Hexokinase 2 (HK2), which catalyzes the first committed step in glucose metabolism, is induced in cancer cells. HK2's role in tumorigenesis has been attributed to its glucose kinase activity. Here, we describe a kinase independent HK2 activity, which contributes to metastasis.

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The E2F transcription factors play a critical role in controlling cell fate. In , the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood.

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Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors.

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Studies in three mouse models of breast cancer identified profound discrepancies between cell-autonomous and systemic Akt1- or Akt2-inducible deletion on breast cancer tumorigenesis and metastasis. Although systemic Akt1 deletion inhibits metastasis, cell-autonomous Akt1 deletion does not. Single-cell mRNA sequencing revealed that systemic Akt1 deletion maintains the pro-metastatic cluster within primary tumors but ablates pro-metastatic neutrophils.

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The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation and differentiation. Here, we profile the larval brain by single-cell RNA-sequencing and identify (), which encodes a cell adhesion protein of the immunoglobulin IgLON family, as regulating the RTK pathway activity during glial cell development. Depletion of Ama reduces cell proliferation, affects glial cell type composition and disrupts the blood-brain barrier (BBB), which leads to hemocyte infiltration and neuronal death.

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In Drosophila, the wing disc-associated muscle precursor cells give rise to the fibrillar indirect flight muscles (IFM) and the tubular direct flight muscles (DFM). To understand early transcriptional events underlying this muscle diversification, we performed single-cell RNA-sequencing experiments and built a cell atlas of myoblasts associated with third instar larval wing disc. Our analysis identified distinct transcriptional signatures for IFM and DFM myoblasts that underlie the molecular basis of their divergence.

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The importance of the retinoblastoma tumor suppressor protein pRB in cell cycle control is well established. However, less is known about its role in differentiation during animal development. Here, we investigated the role of Rbf, the Drosophila pRB homolog, in adult skeletal muscles.

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The function of Retinoblastoma tumor suppressor (pRB) is greatly influenced by the cellular context, therefore the consequences of pRB inactivation are cell-type-specific. Here we employ single cell RNA-sequencing (scRNA-seq) to profile the impact of an Rbf mutation during Drosophila eye development. First, we build a catalogue of 11,500 wild type eye disc cells containing major known cell types.

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To understand the consequences of the complete elimination of E2F regulation, we profiled the proteome of Drosophila dDP mutants that lack functional E2F/DP complexes. The results uncovered changes in the larval fat body, a differentiated tissue that grows via endocycles. We report an unexpected mechanism of E2F/DP action that promotes quiescence in this tissue.

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Article Synopsis
  • The efficiency of processing primary microRNA transcripts (pri-miRNAs) into pre-miRNAs is influenced by the Microprocessor complex, consisting of Drosha and DGCR8, though the mechanisms regulating this have been unclear.
  • Research demonstrates that the Drosophila DGCR8 (Pasha) interacts with the phosphorylated C-terminal domain of RNA polymerase II, affecting how different pri-miRNAs are processed.
  • Blocking Cdk9 activity alters pri-miRNA processing: pri-miRNAs with a UGU sequence are processed more efficiently, while those without it are processed less, indicating that the phosphorylation status of RNA polymerase II plays a crucial role in the recruitment of the Microprocessor complex.
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In this paper, we introduce wide-aperture aspherical lens for high-resolution terahertz (THz) imaging. The lens has been designed and analyzed by numerical methods of geometrical optics and electrodynamics. It has been made of high-density polyethylene by shaping at computer-controlled lathe and characterized using a continuous-wave THz imaging setup based on a backward-wave oscillator and Golay detector.

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The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals.

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The importance of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore coexpressed. The mir-11∼998 cluster consists of two miRNAs, miR-11 and miR-998.

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The family of E2F transcription factors is the key downstream target of the retinoblastoma tumor suppressor protein (pRB), which is frequently inactivated in human cancer. E2F is best known for its role in cell-cycle regulation and triggering apoptosis. However, E2F binds to thousands of genes and, thus, could directly influence a number of biologic processes.

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Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation.

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The importance of microRNAs in the regulation of various aspects of biology and disease is well recognized. However, what remains largely unappreciated is that a significant number of miRNAs are embedded within and are often co-expressed with protein-coding host genes. Such a configuration raises the possibility of a functional interaction between a miRNA and the gene it resides in.

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E2F/DP transcription factors regulate cell proliferation and apoptosis. Here, we investigated the mechanism of the resistance of Drosophila dDP mutants to irradiation-induced apoptosis. Contrary to the prevailing view, this is not due to an inability to induce the apoptotic transcriptional program, because we show that this program is induced; rather, this is due to a mitochondrial dysfunction of dDP mutants.

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The Hippo signaling pathway regulates organ size by controlling the activity of the transcriptional co-activator Yorkie (Yki). Yki is recruited to its target genes by DNA-binding proteins such as Scalloped (Sd). In addition, transcription factor dE2f1, of the Retinoblastoma (Rb) pathway, cooperates with Yki/Sd to synergistically activate a set of common cell cycle target genes.

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