Mason Journals (George Mason Univ.)
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Computational Modeling of Protein-DNA Complexes for Artificial Regulation of Shiga Toxin Expression
No full textSelective DNA-Protein interactions precisely control gene expression. The CI repressor protein binds phage DNA in E. coli and prevents expression of the Shiga toxin. Disrupting this interaction can lead to life-threatening hemolytic uremic syndrome in humans. CI repressor mimetics should, in principle, prevent Shiga toxin production, even when cellular events disfavor native CI binding. De Novo proteins were previously generated to target the DNA encoding the Shiga toxin. These proteins avoid the additional biological regulatory structures associated with the CI protein. By generating model structures with AlphaFold and models of DNA-Protein complexes with Haddock and ChimeraX, this study explored the possibility of correlation between binding mode and affinity. Further, we discuss the implications of comparisons between models of these proteins and their dimeric counterparts, both in terms of affinity prediction and consistency of the predicted binding modes. This work lays a firm foundation for rapid exploration of alternate de novo designs intended to repress the Shiga toxin gene
Seasonality and Salinity Shape Parasite Prevalence in an Estuarine Crab Host
No full textParasite-host dynamics in marine ecosystems are strongly influenced by spatial and temporal conditions. We aimed to investigate how spatiotemporal factors such as salinity and seasonality influenced the prevalence of macroparasites - the entoniscid Cryptocancrion brevibrachium, the rhizocephalan Loxothylacus panopaei, and digenean trematode cysts - in the estuarine crab host, Rhithropanopeus harrisii. Crabs (N=912) were collected from the Chesapeake Bay across a salinity gradient of 10.5ppt-20ppt from August 2024-May 2025. Crabs were dissected, and crab and parasite species were recorded. Linear modeling showed that salinity significantly influenced L. panopaei prevalence but had no effect on C. brevibrachium, cysts, or coinfection prevalence. Trematode cyst prevalence was scarce throughout the year, but prevalence of L. panopaei, C. brevibrachium, and coinfections was higher during warmer months (e.g., summer through early fall). The high prevalence of C. brevibrachium (13%), L. panopaei (40%), and coinfections (12%) found in warmer months is likely associated with high parasite reproduction during this time. Understanding the role that salinity and seasonality play in determining the prevalence of these parasites within this host is important because R. harrisii is an invasive species around the globe and can be used as a vector for these parasites to spread
Fairfax Topographic Accessibility Map
No full textFor people with accessibility challenges, bikers, and runners planning their route, topographic maps provide more information than standard online mapping, allowing users to make more informed decisions to plan easier routes. However, most mapping services do not provide a proper or coherent view of topography. Using Fairfax County as a study area, we create a local street map with elevations represented by filled contours. The webmap is based on USGS Elevation data, boundary data from Fairfax County Open Geospatial Data, and additional boundary data from the City of Fairfax Geohub. All the data are collected for the year 2025. We utilize ArcGIS Online to create the webmap. Using ArcGIS Pro, we further process the elevation data to generate additional layers such as contours to better demonstrate terrain height at various intervals and a slope layer to illustrate the degree of terrain inclination. All these output layers, including the bike network, are exported to ArcGIS Online to configure the webmap application. The final interface is carefully designed to make the webmap accessible and understandable to everyone, without requiring any cartographic knowledge. As a next step, we plan to make this web app publicly available to gather user input on the usability of this web app on a grand scale beyond the Fairfax area. We intend to gain direct input from the goal userbase of bikers, walkers, and users with accessibility challenges, to further optimize and improve the webmap
Cancer Cells Under Oxidative Stress Secrete Extracellular Vesicles Containing Damaged Mitochondrial Components That Can Alter the Death Rate and Mitochondrial Function of Recipient Cells
No full textMitophagy is a critical survival mechanism in which damaged mitochondria are separated into mitophagosomes for degradation via the lysosomes and proteasomes. Extracellular vesicles (EVs) are membrane-bound structures that are secreted into the extracellular space by cells and function as transporters of proteins and nucleic acids between cells. In cancer, EVs have been shown to carry bioactive molecules that impact the biology and function of cancer cells. Under stress, EVs are released by cells, which can bring the damaged mitochondria and signals to other cells. However, no research has been conducted about how EVs from oxidatively stressed cancer cells affect recipient cancer cells. This study addresses this gap in knowledge by examining how EVs from 4T1 breast cancer cells treated with CCCP impact mitochondrial health, ATP production, and caspase-3 activity. We hypothesized that the EVs could transfer damaged mitochondria from the stressed cells to the recipient cells. EVs were isolated from both the CCCP-treated and untreated cells by 2K and 2K+ spins and further purified with IZON columns. The EVs from both treated and untreated cells were used to treat the 4T1 cells, and the MitoTox and Caspase-3/7 assays were performed at the time points 1H, 3H, 6H, ON, and 48H. Compared to the control group, all EV-treated groups showed increased mitochondrial membrane depolarization overnight. ATP production decreased slightly across all EV-treated groups, which suggests less mitochondrial energy output. Caspase-3 activity dropped significantly following overnight treatment. These results support that EVs from oxidatively stressed cancer cells can encourage mitochondrial dysfunction in surrounding cells while also modulating cell death. Understanding the effect that these EVs have on cancer cells can offer insight into how cancer cells adapt under therapeutic pressure
Implications of Governance Models and Regulatory Frameworks on Cryptocurrency Exchange Stability and Risk
No full textCryptocurrency exchanges are central to the functioning and growth of digital asset markets as they facilitate billions in daily trading volume. Yet the regulatory frameworks and governance structures shaping these platforms vary widely and remain poorly documented. Existing methods often rely on volatile, surface-level metrics such as trading volume, which often overlook deeper legal and institutional drivers of exchange behavior, limiting the ability to assess compliance risk and systemic stability. This study addresses that gap by constructing a detailed dataset covering over 250 active and defunct cryptocurrency exchanges worldwide. Each exchange was profiled based on its trading volume, institutional structure, regulatory exposure, and operational characteristics including jurisdictional alignment, governance and ownership models, product architecture, and compliance history. Key findings of the analysis suggest structural features such as ambiguous governance and permissive regulatory environments are associated with more complex product offerings and elevated compliance risks. Preliminary analysis also indicated an independent relationship between trading volume and exchange risk. These patterns suggest that it is the interplay of limited oversight and weak institutional accountability that heightens the likelihood of regulatory breaches. By shifting focus from transactional indicators to institutional design and legal context, this research lays the foundation for more rigorous quantitative analysis of the relationship between cryptocurrency exchange characteristics and their operational performance
An Assessment of Current Private Credits, a form of Real World Assets (RWAs), and their Current Financial Statuses
No full textReal World Assets (RWAs) and their tokenization digitizes several of the key elements of previously non-digitized trading schemes, such as private credit. However, the current market and open internet remains relatively barren with regards to comprehensive analyses of common private credits, which can inhibit due diligence assessment for investing firms or the average person looking to invest their own money into the best possible RWA. The purpose of this paper is to consolidate the findings of a variety of RWA private credit products, which use protocols such as Maple, Goldfinch, and PACT. Operating across Ethereum, Aptos, and ZKsync Era blockchains, these products offer varying yields, asset structures, legal frameworks, and investor access models. Some examples of this are shown because of the fact that different RWA products, such as Syrup USDC, are growing faster than some of their counterparts mentioned further in this paper. This paper aims to consolidate the information from all of those private credits into one location with a simple, easy-to-follow format, in such a way that the reader is able to use the information provided here to fuel their own research or investment as needed
The FACTory: An educational experience on digital misinformation literacy utilizing serious game techniques
No full textBy nature, video games are experiences with a greater level of user interaction, beyond typical mediums such as books or videos. Serious games are games that aim to utilize these special advantages of video games as a learning medium. One growing issue that serious games can address is the rise of misinformation in digital media, especially with new psychological techniques made possible by generative AI and deepfakes. Since preadolescents are particularly susceptible to misinformation, The FACTory serves as an accessible and appealing solution, a serious game that incorporates design principles of experiential learning, meaningful play, and narrative immersion, alongside research on belief formation, source monitoring, and misinformation tactics. Players take the role of a fact-checking content moderator who analyzes digital content and utilizes counter-tactics to resist manipulation techniques. Game features include a grand, overarching narrative and interactive minigames, such as logical reasoning tests and emotional manipulation checks. Although quantitative results have not yet been gathered from prototype testing, by simulating engaging and realistic misinformation scenarios, the game’s design is expected to ensure intrinsic teaching of skepticism, metacognition, and heuristic-driven judgements. Future generations require advanced digital literacy skills that extend beyond current frameworks, and The FACTory offers a scalable model for cultivating critical thinking and responsible citizens of the digital age
Incorporation of PSGL-1 into HIV-1 Virions via Env Exclusion Mechanism Blocks Infectivity
No full textHuman immunodeficiency virus (HIV), a virus that causes acquired immune deficiency syndrome (AIDS). HIV primarily targets immune cells, specifically CD4+ T lymphocytes, for infection, through binding to the CD4 receptor and co-receptors, either CCR5 or CXCR4, on the cell surface. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like surface glycoprotein, is primarily expressed on immune cells and has a role in inflammation. PSGL-1 has been recognized as an HIV restriction factor by blocking HIV infectivity through virion incorporation that sterically hinders virion attachment to target cells. PSGL-1 also inhibits the incorporation of HIV Env into virions by spatially excluding HIV Env. In this study, we have tested the efficiency to PSGL-1 in blocking HIV-1 infectivity. In order to compare the HIV-1 infection, we have packaged a pseudotyped virus in a Lenti vector that expresses green fluorescent protein (GFP), labeled Lenti-turbo-GFP (LTG) and Lenti-turbo-GFP-PSGL-1 (LTGP), along with HIV components such as gag-pol and vesicular stomatitis virus G glycoprotein (VSV-G), as Env in a human cell line, HEK293T cells. On three days of post-infection, we analyzed our data using fluorescent microscopy and flow cytometry, and results suggest a significant decrease in the HIV infection with LTGP virus that expresses PSGL-1. Hence, we could effectively block HIV-1 infection by PSGL-1 in HEK293T cells using LTGP viruses. Therefore, we conclude that PSGL-1 could be used as factor for broad-spectrum HIV-1 restriction
Assessing the Economic Impacts of Disruption to Global Positioning System (GPS) Services
No full textThe Global Position System (GPS) is a satellite-based system that provides precise positioning, navigation, and time determination to many economic actors. As space weather increases in frequency and intensity due to changing space conditions, the risk of potential satellite damage underscores the importance of understanding the economic effects that GPS failures can have on key industries. While advancements in technologies, such as Critical Infrastructure Security and Resilience (CISA) vulnerability assessments, National Institute of Standards and Technology (NIST) profiles, and the Interruption Cost Estimate (ICE) calculator have provided valuable insight into the risks and importance associated with Positioning, Navigation, and Timing (PNT) services, there remains a significant gap in knowledge in the potential economic costs of disruption at different time intervals. Despite past extensive documentation on sectoral dependencies on PNT systems, we lack quantitative modeling that provides industrial sectors with crucial information of expected losses from GPS disruptions. This study includes a time-sequenced quantitative model of effects in different time scenarios due to GPS disruptions for the top 20 industries in the North American Industry Classification System (NAICS). This is achieved by identifying sector-specific dependencies on GPS, and then estimating the economic impacts for various time interval outages, accounting for each sector's contribution to US Gross Domestic Product (GDP). By mapping and analyzing the potential consequences of GPS disruption, this study aims to inform future risk assessments, policymaking, and aid further research in GPS resilient infrastructure
Testing three different compounds as potential anti-inflammatory drugs for the modulation of LTA4H AP activity
No full textLeukotriene A4 hydrolase (LTA4H) is an enzyme affecting neutrophil infiltration in inflammatory diseases like tuberculosis, chronic obstructive pulmonary disease (COPD) and atherosclerosis. LTA4H has two enzymatic pathways: the pro-inflammatory epoxide hydrolase (EH) pathway, where it converts LTA4 to LTB4, and the anti-inflammatory aminopeptidase (AP) pathway, where it cleaves proline-glycine-proline (PGP), the natural substrate of LTA4H, to proline and glycine-proline. Most studies have focused on inhibiting LTA4H’s EH pathway, but fewer studies have focused on promoting its AP pathway. Studies on LTA4H’s AP pathway have mainly been conducted using Ala-pNA as the reporter group because PGP does not have intrinsic fluorescence or absorbance for detection and therefore does not allow for continuous measurements. Herein, we use Pro-pNA as the reporter group, which is more similar to the endogenous PGP structure. For this study, we aimed to determine whether three compounds (B08-2a, B08-2b, and batatasin III), synthesized in our labs, would modulate LTA4H’s AP activity. For the assay, 4-methoxydiphenylmethane (4MDM) and bestatin were used as positive controls for activation or inhibition, respectively. The negative control was treated with buffer alone. Pro-pNA was used as our reporter group. We first produced and purified our LTA4H protein, characterized by a gel electrophoresis, then treated the protein with escalating concentrations of each compound and measured the rate of Pro-pNA cleavage, which was continuously monitored at 405 nm. After analyzing the data, we concluded that B08-2a, B08-2b, and batatasin III inhibit the AP activity with IC50 values of 50.52 μM, 177.68 μM, and 539.04 μM, respectively. More careful assessment and mechanistic characterization of LTA4H enzymatic activities are being pursued to further inform strategies for developing therapeutics for this target. Our next steps will be to test new compounds in order to determine whether any of them will be activators