Biology subjects

Askari, M.

Publications and source records attributed to Askari, M..

3 recordsLinked to original sources

bioRxiv2025

Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at meiotic promoters in mice

Meiotic prophase I characterized by homologous recombination and synapsis is an intricate step for spermatogenesis. This process entails extensive changes to chromatin and transcription. Prior to prophase I, accessible chromatin bound by paused Pol II at meiotic gene promoters is essential for their timely activation later during meiosis. However, the factor responsible for promoting accessible chromatin at meiotic gene promoters before entry into prophase I is unknown. Here, we discovered that NFYA expressed in pre-meiotic germ cells promotes accessible chromatin at meiotic gene promoters including those regulated by STRA8/MEISON axis. Concordantly, conditional germline deletion of Nfya in male mice blocks meiotic entry. Functionally, our spatial and single-cell ATAC-seq data revealed that loss of NFYA in pre-meiotic cells disrupts accessible chromatin at meiotic gene promoters. Our study identifies a pioneer role for NFYA in facilitating accessible chromatin at meiotic gene promoters before meiosis, thereby regulating the timely activation of meiotic genetic program.

developmental biology↗

bioRxiv2024

Emerging Drug Combinations for Targeting Tongue Neoplasms Associated Proteins/Genes: Employing Graph Neural Networks within the RAIN Protocol

BackgroundTongue Neoplasms is a common form of malignancy, with squamous cell carcinoma of the tongue being the most frequently diagnosed type due to regular mechanical stimulation. Its prevalence remains on the rise among neoplastic cancer cases. Finding effective combinations of drugs to target the genetic and protein elements contributing to the development of Managing Tongue Neoplasms poses a difficulty owing to the intricate and varied nature of the ailment. MethodIn this research, we introduce a novel approach using Deep Modularity Networks (DMoN) to identify potential synergistic drug combinations for the condition, following the RAIN protocol. This procedure comprises three primary phases: First, employing Graph Neural Network (GNN) to propose drug combinations for treating the ailment by extracting embedding vectors of drugs and proteins from an extensive knowledge graph containing various biomedical data types, such as drug-protein interactions, gene expression, and drug-target interactions. Second, utilizing natural language processing to gather pertinent articles from clinical trials involving the previously recommended drugs. Finally, conducting network meta-analysis to evaluate the comparative efficacy of these drug combinations. ResultWe utilized our approach on a dataset containing drugs and genes as nodes, connected by edges indicating their associated p-values. Our DMoN model identified Cisplatin, Bleomycin, and Fluorouracil as the optimal drug combination for targeting the human genes/proteins associated with this cancer. Subsequent scrutiny of clinical trials and literature confirmed the validity of our findings. Additionally, network meta-analysis substantiated the efficacy of these medications concerning the pertinent genes. ConclusionThrough the utilization of DMoN as part of the RAIN protocol, our method introduces a fresh and effective way to suggest notable drug combinations for addressing proteins/genes linked to Tongue Neoplasms. This approach holds promise in assisting healthcare practitioners and researchers in pinpointing the best treatments for patients, as well as uncovering the fundamental mechanisms of the disease. HighlightsO_LIA new method using Deep Modularity Networks and the RAIN protocol can find the best drug combinations for treating Tongue Neoplasms, a common and deadly form of cancer. C_LIO_LIThe method uses a Graph Neural Network to suggest drug pairings from a large knowledge graph of biomedical data, then searches for clinical trials and performs network meta-analysis to compare their effectiveness. C_LIO_LIThe method discovered that Cisplatin, Bleomycin, and Fluorouracil are suitable drugs for targeting the genes/proteins involved in this cancer, and confirmed this finding with literature review and statistical analysis. C_LIO_LIThe method offers a novel and powerful way to assist doctors and researchers in finding the optimal treatments for patients with Tongue Neoplasms, and to understand the underlying causes of the disease. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/598402v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@56bc74org.highwire.dtl.DTLVardef@6e9308org.highwire.dtl.DTLVardef@177144aorg.highwire.dtl.DTLVardef@d53c5e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2

Antiviral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Coppers antiviral properties have been widely documented; but the antiviral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). Copper and copper oxide surfaces exhibited superior anti-SARS-CoV-2 activity; however, level of antiviral activity was dependent upon the composition of the carrier solution used to deliver virus inoculum. We demonstrate that copper ions released into solution from test surfaces can mediate virus inactivation, indicating a copper ion dissolution-dependent antiviral mechanism. Level of antiviral activity is, however, not dependent on the amount of copper ions released into solution per se. Instead, our findings suggest that degree of virus inactivation is dependent upon copper ion complexation with other biomolecules (e.g., proteins/metabolites) in the virus carrier solution that compete with viral components. Although using tissue culture-derived virus inoculum is experimentally convenient to evaluate the antiviral activity of copper-derived test surfaces, we propose that the high organic content of tissue culture medium reduces the availability of "uncomplexed" copper ions to interact with the virus, negatively affecting virus inactivation and hence surface antiviral performance. We propose that laboratory antiviral surface testing should include virus delivered in a physiologically relevant carrier solution (saliva or nasal secretions when testing respiratory viruses) to accurately predict real-life surface antiviral performance when deployed in public spaces. ImportanceThe purpose of evaluating antiviral activity of test surfaces in the laboratory is to identify surfaces that will perform efficiently in preventing fomite transmission when deployed on high-traffic touch surfaces in public spaces. The conventional method in laboratory testing is to use tissue culture-derived virus inoculum, however this study demonstrates that antiviral performance of test copper-containing surfaces is dependent on the composition of the carrier solution in which the virus inoculum is delivered to test surfaces. Therefore, we recommend that laboratory surface testing should include virus delivered in a physiologically relevant carrier solution, to accurately predict real-life test surface performance in public spaces. Understanding the mechanism of virus inactivation is key to future rational design of improved antiviral surfaces. Here, we demonstrate that copper ions released from copper surfaces into small liquid droplets containing SARS-CoV-2, is a mechanism by which the virus that causes COVID-19 can be inactivated.

microbiology↗