All Faculty Deposits

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The "All Faculty Deposits" collection contains works deposited by faculty and appointed delegates from the Elements (EFARs) system. For help with Elements, see Frequently Asked Questions on the Provost's website. In general, items can only be deposited if the item is a scholarly article that is covered by Virginia Tech's open access policy, or the item is openly licensed or in the public domain, or the item is permitted to be posted online under the journal/publisher policy, or the depositor owns the copyright. See Right to Deposit on the VTechWorks Help page. If you have questions email us at vtechworks@vt.edu.

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Effect of stressors during COVID-19 lockdown on malnutrition and health-risk behaviors among Jordanian college students: A cross-sectional study
Alkhalidy, Hana; Al-Shami, Islam; Alnaser, Khadeejah; Alkharabsheh, Ana'am; Nawaiseh, Hala; Liu, Dongmin (LIPPINCOTT WILLIAMS & WILKINS, 2024-10-11)
A stressful condition such as the emergence of the coronavirus and its related lockdown measures might trigger alterations in college students' behaviors. This cross-sectional study aimed to identify the changes in college students' dietary and lifestyle behaviors during the lockdown and the effect of lockdown-related stressors on health-risk behaviors. A web-based survey was conducted among undergraduate college students in Jordan. Weight and height were reported by the students. The students' dietary and lifestyle behaviors and their changes during 1 month of the countrywide lockdown were assessed. The Perceived Stress Scale-4 was utilized to assess stress levels. Results indicated that 77.2% of the students reported weight changes. Notably, 45.9% increased their intake of unhealthy food, while and 38% opted for healthier food choices. Most students experienced alterations in physical activity (80.0%), screen time (86.2%), smoking, and sleep patterns (85.4%), with a higher tendency toward adopting health-risk behaviors. Perceptions of curfew-related stress were associated with distance learning-related stress (OR = 2.73, CI: 1.08-6.90, P = .034), and a greater change in physical activity (OR = 3.59, CI: 1.36-9.48, P = .010). Additionally, weight changes were associated with perception of other types of stressors (OR = 3.39, CI: 1.39-8.28, P = .007). Overall, there was a considerable increase in malnutrition and health-risk behaviors among students during the lockdown. Understanding students' responses to these stressful conditions and the role of stress in driving behavioral changes are crucial for developing interventions that enhance college students' adaptation to such changes and maintaining healthy dietary and lifestyle behaviors in the future.
Conservation of a chromosome 8 inversion and exon mutations suggest a common gulonolactone oxidase gene evolution among primates, including H. Neanderthalis
Good, Deborah; Manseuto, Alexander (SPRINGER, 2024-06)
Ascorbic acid functions as an antioxidant and facilitates other biochemical processes such as collagen triple helix formation, and iron uptake by cells. Animals which endogenously produce ascorbic acid have a functional gulonolactone oxidase gene (GULO); however, humans have a GULO pseudogene (GULOP) and depend on dietary ascorbic acid. In this study, the conservation of GULOP sequences in the primate haplorhini suborder were investigated and compared to the GULO sequences belonging to the primates strepsirrhini suborder. Phylogenetic analysis suggested that the conserved GULOP exons in the haplorhini primates experienced a high rate of mutations following the haplorhini/strepsirrhini divergence. This high mutation rate has decreased during the evolution of the haplorhini primates. Additionally, indels of the haplorhini GULOP sequences were conserved across the suborder. A separate analysis for GULO sequences and well-conserved GULOP sequences focusing on placental mammals identified an in-frame GULO sequence in the Brazilian guinea pig, and a potential GULOP sequence in the pika. Similar to haplorhini primates, the guinea pig and lagomorph species have experienced a high substitution rate when compared to the mammals used in this study. A shared synteny to examine the conservation of local genes near GULO/GULOP identified a conserved inversion around the GULO/GULOP locus between the haplorhini and strepsirrhini primates. Fischer’s exact test did not support an association between GULOP and the chromosomal inversion. Mauve alignment showed that the inversion of the length of the syntenic block that the GULO/GULOP genes belonged to was variable. However, there were frequent rearrangements around ~ 2 million base pairs adjacent to GULOP involving the KIF13B and MSRA genes. These data may suggest that genes acquiring deleterious mutations in the coding sequence may respond to these deleterious mutations with rapid substitution rates.
404 Not Found: Quantitative Methods in Disability Studies
Blanchard, Aurelian; Blanchard, Enka; Shew, Ashley (SAGE, 2024-11-04)
Disability is sometimes theorised as existing between the world (including social norms and infrastructure) and the person (who gets labelled disabled in a ‘misfit’ between the world and them). Disability is often enacted through data systems and infrastructures and the history of disability studies reflects a fight against such systems. In this paper, we examine the fraught relationships between disability studies and data science — from institutions and historical marginalisation to current practices of policing and surveillance. We critique the resulting preeminence of qualitative methods in disability studies as one impediment to translating disability studies to data scientists and to effective policy-making. We then address hopeful movements to crip data studies, looking at work on AI and disability bias, crip technoscience, counterventional research, and cripped data.
Why pursue a career in teaching agriculture? Application of self-determination theory and the theory of planned behavior
Hur, Gangseok; Barry, Debra M.; Katrina, Alford; Jagger, Carla B.; Roberts, T. Grady (2024-06-30)
Given the shortage of agriculture teachers across the country, understanding individuals’ motivation to pursue a career in teaching agricultural education is critical to developing strategies for teacher recruitment and teacher education. Several studies have investigated factors that motivate preservice and in-service agriculture teachers to pursue a career teaching agricultural education based on the Factors Influencing Teaching Choice (FIT-Choice) model. However, little research investigated the topic using different theoretical lenses or a mixed-methods approach, which could provide new perspectives on individuals’ motivation to teach. To address the knowledge gap, we investigated Florida preservice teacher recruitment program participants’ motivation to teach agricultural education using a mixed-methods approach from the self-determination theory and the theory of planned behavior theoretical lens. We found that individuals’ intention to become agriculture teachers was statistically significantly explained by two predictors: attitude toward behavior and perceived behavioral control regarding a career in teaching agriculture. When choosing a career in teaching agriculture, the score for more self-determined motivation was substantially higher than that for less self-determined motivation. Furthermore, inspiring agriculture teachers, positive experiences with SBAE programs, a passion for teaching and agriculture, and paying it forward to students were the main factors that motivated them to pursue a career in teaching agricultural education. Based on the theoretical frameworks and the results, a model for understanding factors influencing individuals to pursue a career in teaching agriculture was proposed to broaden our understanding of the multidimensional nature of individuals’ motivation to teach agriculture.
Stochastic Boolean model of normal and aberrant cell cycles in budding yeast
Taoma, Kittisak; Tyson, John J.; Laomettachit, Teeraphan; Kraikivski, Pavel (Nature Portfolio, 2024-10-18)
The cell cycle of budding yeast is governed by an intricate protein regulatory network whose dysregulation can lead to lethal mistakes or aberrant cell division cycles. In this work, we model this network in a Boolean framework for stochastic simulations. Our model is sufficiently detailed to account for the phenotypes of 40 mutant yeast strains (83% of the experimentally characterized strains that we simulated) and also to simulate an endoreplicating strain (multiple rounds of DNA synthesis without mitosis) and a strain that exhibits ‘Cdc14 endocycles’ (periodic transitions between metaphase and anaphase). Because our model successfully replicates the observed properties of both wild-type yeast cells and many mutant strains, it provides a reasonable, validated starting point for more comprehensive stochastic-Boolean models of cell cycle controls. Such models may provide a better understanding of cell cycle anomalies in budding yeast and ultimately in mammalian cells.
A perturbation approach for refining Boolean models of cell cycle regulation
Banerjee, Anand; Rahaman, Asif Iqbal; Mehandale, Alok; Kraikivski, Pavel (PLOS, 2024-09-06)
Considerable effort is required to build mathematical models of large protein regulatory networks. Utilizing computational algorithms that guide model development can significantly streamline the process and enhance the reliability of the resulting models. In this article, we present a perturbation approach for developing data-centric Boolean models of cell cycle regulation. To evaluate networks, we assign a score based on their steady states and the dynamical trajectories corresponding to the initial conditions. Then, perturbation analysis is used to find new networks with lower scores, in which dynamical trajectories traverse through the correct cell cycle path with high frequency. We apply this method to refine Boolean models of cell cycle regulation in budding yeast and mammalian cells.
Subjective Assessments of Arm-Support Exoskeletons During Simulated Static and Dynamic Overhead Tasks
Morris, Wallace; Kim, Sunwook; Ojelade, Aanuoluwapo; Srinivasan, Divya; Smets, Marty; Nussbaum, Maury A. (SAGE Publications, 2022-10-27)
Multimodal Feedback to Improve Performance of Order Picker Truck Drivers Using a Virtual Reality Simulator
Islam, Md Shafiqul; Hsing, Hsiang-Wen; Kim, Sunwook; Lau, Nathan; Nussbaum, Maury A.; Lim, Sol (SAGE Publications, 2024-10-21)
VR technology presents exciting prospects for immersive forklift training environments. VR facilitates hands-on learning without the risks of real world errors. Real-time multimodal feedback (such as visual and haptic) is an effective way to enhance learning outcomes and skill acquisition. However, the efficacy and usability of real-time multimodal feedback provided for VR-based forklift driving needs to be investigated, as its impact on training outcomes remains unexplored. We aim to understand how various feedback modalities influence task performance, perceived workload, and user preferences. Fifteen (3 female, 12 male) individuals participated and completed VR-based forklift driving tasks with four feedback conditions (No feedback, visual, haptic, combined visual and haptic). A significant main effect of Feedback was found for completion time. Mental demand and frustration were affected by the Sex and Feedback interaction. These differences in the perception of feedback modalities underscore the importance of considering diverse user demographics when designing feedback systems.
FaaSr: Cross-Platform Function-as-a-Service Serverless Scientific Workflows in R
Park, Sungjae; Thomas, R. Quinn; Carey, Cayelan C.; Delany, Austin D.; Ku, Yun-Jung; Lofton, Mary E.; Figueiredo, Renato J. (IEEE, 2024-09)
Modern Function-as-a-Service (FaaS) cloud platforms offer great potential for supporting event-driven scientific workflows. Nonetheless, there remain barriers to adoption by the scientific community in domains such as environmental sciences, where R is the focal language used for the development of applications and where users are typically not well-versed with FaaS APIs. This paper describes the design and implementation of FaaSr, a novel middleware system that supports event-driven scientific workflows in R. A key novelty in FaaSr is the ability to deploy workflows across FaaS providers without the need for any managed servers for coordination. With FaaSr: 1) functions are written in R; 2) the runtime environments for their execution are customizable containers; 3) functions access data in cloud storage (S3) with a familiar file-based abstraction supporting both full file put/get primitives and subsetting using the Parquet format; and 4) function invocation and workflow coordination only requires S3 cloud object storage, without relying on any dedicated, active workflow engine server or cloud-specific queues/databases. The paper reports on the functionality and performance of FaaSr for micro-benchmarks and two case studies: event-driven forecast and batch job workflows. These demonstrate the ability to deploy workflows across multiple platforms (GitHub Actions, Amazon Web Services Lambda, and the open-source OpenWhisk), without the need for dedicated coordination servers, across both cloud and edge resources. FaaSr is open-source and available as a CRAN package.
An in vitro evaluation of intravenous lipid emulsion on three common canine toxicants
Jones, Emery; Walton, Stuart A.; Davis, Jennifer; Council-Troche, McAlister (Frontiers, 2024-09-25)
Objective: To determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time. Animals: Seven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group). Procedures: Injectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, Intralipid®) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 g for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at −80°C prior to analysis. Results: A significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration. Conclusion: ILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment in vitro study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis.
The Chemistry of the Defensive Secretions of Three Species of Millipedes in the Genus Brachycybe
Banks, Paige; Funkhouser, Emma M.; Macias, Angie M.; Lovett, Brian; Meador, Shelby; Hatch, Arden; Garraffo, H. Martin; Cartwright, Kaitie C.; Kasson, Matt T.; Marek, Paul E.; Jones, Tappey H.; Mevers, Emily (Springer, 2024-06-10)
Millipedes have long been known to produce a diverse array of chemical defense agents that deter predation. These compounds, or their precursors, are stored in high concentration within glands (ozadenes) and are released upon disturbance. The subterclass Colobognatha contains four orders of millipedes, all of which are known to produce terpenoid alkaloids—spare the Siphonophorida that produce terpenes. Although these compounds represent some of the most structurally-intriguing millipede-derived natural products, they are the least studied class of millipede defensive secretions. Here, we describe the chemistry of millipede defensive secretions from three species of Brachycybe: Brachycybe producta, Brachycybe petasata, and Brachycybe rosea. Chemical investigations using mass spectrometry-based metabolomics, chemical synthesis, and 2D NMR led to the identification of five alkaloids, three of which are new to the literature. All identified compounds are monoterpene alkaloids with the new compounds representing indolizidine (i.e. hydrogosodesmine) and quinolizidine alkaloids (i.e. homogosodesmine and homo-hydrogosodesmine). The chemical diversity of these compounds tracks the known species phylogeny of this genus, rather than the geographical proximity of the species. The indolizidines and quinolizidines are produced by non-sympatric sister species, B. producta and B. petasata, while deoxybuzonamine is produced by another set of non-sympatric sister species, B. rosea and Brachycybe lecontii. The fidelity between the chemical diversity and phylogeny strongly suggests that millipedes generate these complex defensive agents de novo and begins to provide insights into the evolution of their biochemical pathways.
Discovery of Biofilm Inhibitors from the Microbiota of Marine Egg Masses
Kyei, Lois; Piedl, Karla; Miller, Eleanor M.; Mevers, Emily (American Chemical Society, 2024-05-30)
Biofilms commonly develop in immunocompromised patients, which leads to persistent infections that are difficult to treat. In the biofilm state, bacteria are protected against both antibiotics and the host’s immune system; currently, there are no therapeutics that target biofilms. In this study, we screened a chemical fraction library representing the natural product capacity of the microbiota of marine egg masses, namely, the moon snail egg collars. This led to the identification of active fractions targeting both Pseudomonas aeruginosa and Staphylococcus aureus biofilms. Subsequent analysis revealed that a subset of these fractions were capable of eradicating preformed biofilms, all against S. aureus. Bioassay-guided isolation led us to identify pseudochelin A, a known siderophore, as a S. aureus biofilm inhibitor with an IC50 of 88.5 μM. Mass spectrometry-based metabolomic analyses revealed widespread production of pseudochelin A among fractions possessing S. aureus antibiofilm properties. In addition, a key biosynthetic gene involved in producing pseudochelin A was detected on 30% of the moon snail egg collars and pseudochelin A is capable of inhibiting the formation of biofilms (IC50 50.6 μM) produced by ecologically relevant bacterial strains. We propose that pseudochelin A may have a role in shaping the microbiome or protecting the egg collars from microbiofouling.
Design, Synthesis, and Antifungal Activity of 3-substituted-2(5H)-Oxaboroles
Campbell, Rose; Buchbinder, Nicklas W. ; Szwetkowski, Connor; Zhu, Yumeng; Piedl, Karla; Truong, Mindy; Matson, John B.; Santos, Webster L.; Mevers, Emily (American Chemical Society, 2024-02-22)
Next generation antimicrobial therapeutics are desperately needed as new pathogens with multiple resistance mechanisms continually emerge. Two oxaboroles, tavaborole and crisaborole, were recently approved as topical treatments for onychomycosis and atopic dermatitis, respectively, warranting further studies into this privileged structural class. Herein, we report the antimicrobial properties of 3-substituted-2(5H)-oxaboroles, an unstudied family of medicinally relevant oxaboroles. Our results revealed minimum inhibitory concentrations as low as 6.25 and 5.20 μg/mL against fungal (e.g., Penicillium chrysogenum) and yeast (Saccharomyces cerevisiae) pathogens, respectively. These oxaboroles were nonhemolytic and nontoxic to rat myoblast cells (H9c2). Structure-activity relationship studies suggest that planarity is important for antimicrobial activity, possibly due to the effects of extended conjugation between the oxaborole and benzene rings.
Neuromodulating Alkaloids from Millipede Defensive Secretions
Menegatti, Carla; Wood, Jared S.; Banks, Paige; Knott, Kenneth; Briganti, Jonathan S.; Briganti, Anthony J.; McNally, Samuel V. G.; Marek, Paul E.; Brown, Anne M.; Jones, Tappey H.; Williamson, R. Thomas; Mevers, Emily (American Chemical Society, 2024)
Millipedes have long been known to produce structurally diverse chemical defenses, including hydrogen cyanide, terpenoid alkaloids, and oxidized aromatics. Although the hydrogen cyanide and oxidized aromatic producing millipedes have been well studied, less than 10% of the terpenoid alkaloid producers have been chemically investigated. Several previous studies have shown that alkaloids disorient predators, but their biochemical target is currently unknown. Herein, we investigated the defensive secretions of a colobognath millipede, Ischnocybe plicata, and elucidated the constitution, absolute configuration, and conformation of four new highly oxidized terpenoid alkaloids, termed ischnocybines, using a range of analytical techniques. The ischnocybines are actively secreted from the defensive glands and were shown to disorient ants, a likely common predator. Evaluation of the ischnocybines in a panel of neuroreceptors revealed that ischnocybine A possesses potent (Ki 13.6 nM) and selective (100-fold) binding affinity for sigma-1, an orphan neuroreceptor, over sigma-2. These molecules represent the most complex alkaloids to be discovered from millipedes and provide the first potential insights into a biochemical target responsible for their defensive properties.
The microbiota of moon snail egg collars is shaped by host-specific factors
Piedl, Karla; Aylward, Frank O.; Mevers, Emily (American Society for Microbiology, 2024-10-04)
Moon snails (Family: Naticidae) lay eggs using a mixture of mucus and sediment to form an egg mass commonly referred to as an egg collar. These egg collars do not appear to experience micro-biofouling or predation, and this observation led us to hypothesize that the egg collars possess a chemically rich microbiota that protect the egg collars from pathogens. Herein, we sought to gain an understanding of the bacterial composition of egg collars laid by a single species of moon snails, Neverita delessertiana, by amplifying and sequencing the 16S rRNA gene from the egg collar and sediment samples collected at four distinct geographical regions in southwest Florida. Relative abundance and non-metric multidimensional scaling plots revealed distinct differences in the bacterial composition between the egg collar and sediment samples. In addition, the egg collars had a lower α-diversity than the sediment, with specific genera being significantly enriched in the egg collars. Analysis of microorganisms consistent across two seasons suggests that Flavobacteriaceae make up a large portion of the core microbiota (36%-58% of 16S sequences). We also investigated the natural product potential of the egg collar microbiota by sequencing a core biosynthetic gene, the adenylation domains (ADs), within the gene clusters of non-ribosomal peptide synthetase (NRPS). AD sequences matched multiple modules within known NRPS gene clusters, suggesting that these compounds might be produced within the egg collar system. This study lays the foundation for future studies into the ecological role of the moon snail egg collar microbiota. IMPORTANCE Animals commonly partner with microorganisms to accomplish essential tasks, including chemically defending the animal host from predation and/or infections. Understanding animal-microbe partnerships and the molecules used by the microbe to defend the animals from pathogens or predation has the potential to lead to new pharmaceutical agents. However, very few of these systems have been investigated. A particularly interesting system is nutrient-rich marine egg collars, which often lack visible protections, and are hypothesized to harbor beneficial microbes that protect the eggs. In this study, we gained an understanding of the bacterial strains that form the core microbiota of moon snail egg collars and gained a preliminary understanding of their natural product potential. This work lays the foundation for future work to understand the ecological role of the core microbiota and to study the molecules involved in chemically defending the moon snail eggs.
Bokeelamides: Lipopeptides from Bacteria Associated with Marine Egg Masses
Campbell, Rose; Kyei, Lois; Piedl, Karla; Zhang, Zheye; Chen, Ming; Mevers, Emily (American Chemical Society, 2024-11)
Moon snails (family: Naticidae) lay egg masses that are rich in bacterial species distinct from the surrounding environment. We hypothesized that this microbiome chemically defends the moon snail eggs from predation and pathogens. Herein, we report the discovery of bokeelamides, new lipopeptides from the egg mass-associated bacterium, Ectopseudomonas khazarica, which were discovered using mass spectrometry (MS)-based metabolomics. The structures of the bokeelamides were elucidated using two-dimensional (2D) nuclear magnetic resonance (NMR), tandem MS, Marfey’s, and genomic analyses.
Case report: Placental chorioadenoma in a primiparous pug dog
Balogh, Orsolya; Diab, Santiago; Parker, Acadia; de Sousa, Gabriela C.; Cecere, Julie T.; McCarter, Samantha J.; Sponenberg, Dan Phillip (Frontiers, 2024-11-27)
A single 1.7 cm × 1.2 cm × 1 cm focal, raised, smooth, round, pink to flesh-colored mass protruding from the chorioallantois of the zonary placenta was found during Cesarean section in a primiparous pug bitch. Microscopically, the non-encapsulated, non-infiltrative, exophytic mass originated from the chorioallantoic stroma overlying the labyrinth and was composed of many arborizing fronds generally lined by 1 to 2 layers of cuboidal, columnar and occasionally polygonal, large trophoblastic cells, but frequently by a larger number of cells that occasionally piled up to form small nests or nodules. The gross and microscopic characteristics of this mass were compatible with a benign neoplastic process arising in the chorioallantois and involving placental trophoblasts, hence the diagnosis of a placental chorioadenoma. Five of the six newborn puppies were viable and of normal birthweight, while one puppy, which had lower birthweight than the others, could not be resuscitated and was humanely euthanized. Although placental tumors in dogs are very rare, this case is compelling evidence in the argument for routine inspection of canine placentas to identify potentially deleterious macro- or microscopic conditions that may be linked to negative fetal outcomes.
Phosphorylation of Ser711 Residue in the Hypervariable Region of Zoonotic Genotype 3 Hepatitis E Virus is Important for Virus Replication
Wang, Bo; Subramaniam, Sakthivel; Tian, Debin; Mahsoub, Hassan M.; Heffron, C. Lynn; Meng, Xiang-Jin (American Society for Microbiology, 2024-10-08)
Hepatitis E virus (HEV) is distinct from other hepatotropic viruses because it is zoonotic. HEV-1 and HEV-2 exclusively infect humans, whereas HEV-3 and HEV-4 are zoonotic. However, the viral and/or host factors responsible for cross-species HEV transmission remain elusive. The hypervariable region (HVR) in HEV is extremely heterogenetic and is implicated in HEV adaptation. Here, we investigated the potential role of Serine phosphorylation in the HVR in HEV replication. We first analyzed HVR sequences across different HEV genotypes and identified a unique region at the N-terminus of the HVR, which is variable in the human-exclusive HEV genotypes but relatively conserved in zoonotic HEV genotypes. Using predictive tools, we identified four potential phosphorylation sites that are highly conserved in zoonotic HEV-3 and HEV-4 genomes but absent in human-exclusive HEV-1 strains. To explore the functional significance of these putative phosphorylation sites, we introduced mutations into the HEV-3 infectious clone and indicator replicon, replacing each Serine residue individually with alanine or aspartic acid, and assessed the impact of these substitutions on HEV-3 replication. We found that the phospho-blatant S711A mutant significantly reduced virus replication, whereas the phospho-mimetic S711D mutant modestly reduced virus replication. Conversely, mutations in the other three Serine residues did not significantly affect HEV-3 replication. Furthermore, we demonstrated that Ser711 phosphorylation did not alter host cell tropism of zoonotic HEV-3. In conclusion, our results showed that potential phosphorylation of the Ser711 residue significantly affects HEV-3 replication in vitro, providing new insights into the potential mechanisms of zoonotic HEV transmission.
The role of gut microbiota in different murine models of systemic lupus erythematosus
Lu, Ran; Luo, Xin M. (Taylor & Francis, 2024-07-16)
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.
TCDD and CH223191 alter T cell balance but fail to induce anti-inflammatory response in adult lupus mice
Gutierrez, Fernando; Murphy, Quiyana M.; Swartwout, Brianna K.; Read, Kaitlin A.; Edwards, Michael R.; Abdelhamid, Leila; Cabana-Puig, Xavier; Testerman, James C.; Xu, Tian; Lu, Ran; Amin, Pavly; Cecere, Thomas E.; Reilly, Christopher M.; Oestreich, Kenneth J.; Ciupe, Stanca M.; Luo, Xin M. (The American Association of Immunologists, 2024-02-14)
Aryl hydrocarbon receptor (AhR) responds to endogenous and exogenous ligands as a cytosolic receptor, transcription factor, and E3 ubiquitin ligase. Several studies support an anti-inflammatory effect of AhR activation. However, exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early stages of development results in an autoimmune phenotype and exacerbates lupus. The effects of TCDD on lupus in adults with pre-existing autoimmunity have not been described. We present novel evidence that AhR stimulation by TCDD alters T cell responses but fails to impact lupus-like disease using an adult mouse model. Interestingly, AhR antagonist CH223191 also changed T cell balance in our model. We next developed a conceptual framework for identifying cellular and molecular factors that contribute to physiological outcomes in lupus and created models that describe cytokine dynamics that were fed into a system of differential equations to predict the kinetics of T follicular helper (Tfh) and regulatory T (Treg) cell populations. The model predicted that Tfh cells expanded to larger values following TCDD exposure compared with vehicle and CH223191. Following the initial elevation, both Tfh and Treg cell populations continuously decayed over time. A function based on the ratio of predicted Treg/Tfh cells showed that Treg cells exceed Tfh cells in all groups, with TCDD and CH223191 showing lower Treg/Tfh cell ratios than the vehicle and that the ratio is relatively constant over time. We conclude that AhR ligands did not induce an anti-inflammatory response to attenuate autoimmunity in adult lupus mice. This study challenges the dogma that TCDD supports an immunosuppressive phenotype.

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