Biology subjects

Shimoyama, M.

Publications and source records attributed to Shimoyama, M..

3 recordsLinked to original sources

bioRxiv2024

EhRacM differentially regulates macropinocytosis and motility in the enteric protozoan parasite Entamoeba histolytica

Macropinocytosis is an evolutionarily conserved endocytic process that plays a vital role in internalizing extracellular fluids and particles in cells. This non-selective endocytic pathway is crucial for various physiological functions such as nutrient uptake, sensing, signaling, antigen presentation, and cell migration. While macropinocytosis has been extensively studied in macrophages and cancer cells, the molecular mechanisms of macropinocytosis in pathogens are less understood. It has been known that Entamoeba histolytica, the causative agent of amebiasis, exploits macropinocytosis for survival and pathogenesis. Since macropinocytosis is initiated by actin polymerization, leading to the formation of membrane ruffles and the subsequent trapping of solutes in macropinosomes, actin cytoskeleton regulation is crucial. Thus, this study focuses on unraveling the role of well-conserved actin cytoskeleton regulators, Rho small GTPase family proteins, in macropinocytosis in E. histolytica. Through gene silencing of highly transcribed Ehrho/Ehrac genes and following flow cytometry analysis, we identified that silencing EhracM enhances dextran macropinocytosis and affects cellular migration persistence. Live imaging and interactome analysis unveiled the cytosolic and vesicular localization of EhRacM, along with its interaction with signaling and membrane traffic-related proteins, shedding light on EhRacMs multiple roles. Our findings provide insights into the specific regulatory mechanisms of macropinocytosis among endocytic pathways in E. histolytica, highlighting the significance of EhRacM in both macropinocytosis and cellular migration. Author SummaryEntamoeba histolytica is an intestinal protozoan parasite that causes amoebic dysentery and liver abscesses in humans. This organism exploits macropinocytosis, a cellular process that engulfs extracellular fluids and particles, for its survival and pathogenicity. Although macropinocytosis is well-characterized in immune cells and cancer cells as it is essential for nutrient uptake, its mechanisms in pathogens, such as E. histolytica, remain less explored. Our research focused on the molecular mechanisms underpinning macropinocytosis in this parasite, specifically examining the role of Rho small GTPase family proteins. These proteins are critical regulators of the actin cytoskeleton in eukaryotic cells. Our study reveals that one specific Rho small GTPase, EhRacM, is in the maturation of macropinosomes as well as in directing linear cell migration. The physiological significance of EhRacM in regulating both macropinocytosis and migration opens new avenues for understanding the role of Rho small GTPases in these signaling pathways, which could eventually lead to the development of new control measures against diseases caused by this parasite.

cell biology↗

bioRxiv2019

FAIRshake: toolkit to evaluate the findability, accessibility, interoperability, and reusability of research digital resources

As more datasets, tools, workflows, APIs, and other digital resources are produced by the research community, it is becoming increasingly difficult to harmonize and organize these efforts for maximal synergistic integrated utilization. The Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles have prompted many stakeholders to consider strategies for tackling this challenge by making these digital resources follow common standards and best practices so that they can become more integrated and organized. Faced with the question of how to make digital resources more FAIR, it has become imperative to measure what it means to be FAIR. The diversity of resources, communities, and stakeholders have different goals and use cases and this makes assessment of FAIRness particularly challenging. To begin resolving this challenge, the FAIRshake toolkit was developed to enable the establishment of community-driven FAIR metrics and rubrics paired with manual, semi- and fully-automated FAIR assessment capabilities. The FAIRshake toolkit contains a database that lists registered digital resources, with their associated metrics, rubrics, and assessments. The FAIRshake toolkit also has a browser extension and a bookmarklet that enables viewing and submitting assessments from any website. The FAIR assessment results are visualized as an insignia that can be viewed on the FAIRshake website, or embedded within hosting websites. Using FAIRshake, a variety of bioinformatics tools, datasets listed on dbGaP, APIs registered in SmartAPI, workflows in Dockstore, and other biomedical digital resources were manually and automatically assessed for FAIRness. In each case, the assessments revealed room for improvement, which prompted enhancements that significantly upgraded FAIRness scores of several digital resources.

bioinformatics↗

bioRxiv2019

PhenoGeneRanker: A Tool for Gene Prioritization Using Complete Multiplex Heterogeneous Networks

Uncovering genotype-phenotype relationships is a fundamental challenge in genomics. Gene prioritization is an important step for this endeavor to make a short manageable list from a list of thousands of genes coming from high-throughput studies. Network propagation methods are promising and state of the art methods for gene prioritization based on the premise that functionally-related genes tend to be close to each other in the biological networks.\n\nIn this study, we present PhenoGeneRanker, an improved version of a recently developed network propagation method called Random Walk with Restart on Multiplex Heterogeneous Networks (RWR-MH). PhenoGeneRanker allows multi-layer gene and disease networks. It also calculates empirical p-values of gene ranking using random stratified sampling of genes based on their connectivity degree in the network.\n\nWe ran PhenoGeneRanker using multi-omics datasets of rice to effectively prioritize the cold tolerance-related genes. We observed that top genes selected by PhenoGeneRanker were enriched in cold tolerance-related Gene Ontology (GO) terms whereas bottom ranked genes were enriched in general GO terms only. We also observed that top-ranked genes exhibited significant p-values suggesting that their rankings were independent of their degree in the network.\n\nCCS CONCEPTS* Bioinformatics * Biological networks * System biology * Computational genomics\n\nAvailability and implementationThe source code is available on GitHub at https://github.com/bozdaglab/PhenoGeneRanker under Creative Commons Attribution 4.0 license\n\nContactcdursun@mcw.edu or serdar.bozdag@marquette.edu

bioinformatics↗