Digital Commons Network^™

Spatial Metabolomics Reveals Glycogen As An Actionable Target For Pulmonary Fibrosis, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Samuel Santos Valenca, Qi Sun, Tara R. Hawkinson, Lyndsay E. A. Young, Juanita E. Ferreira, Autumn V. Hammonds, Jaclyn B. Dunne, Robert J. Mcdonald, Kimberly J. Absher, Brittany Dong, Ronald C. Bruntz, Kia H. Markussen, Jelena A. Juras, Warren J. Alilain, Jinze Liu, Matthew S. Gentry, Peggi M. Angel, Christopher M. Waters, Ramon C. Sun

Saha Cardiovascular Research Center Faculty Publications

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high- dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed …

The Plod2/Succinate Axis Regulates The Epithelial–Mesenchymal Plasticity And Cancer Cell Stemness, Yuxin Tong, Yifei Qi, Gaofeng Xiong, Junyan Li, Timothy L. Scott, Jie Chen, Daheng He, Linzhang Li, Chi Wang, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate …

Piloting An Oral History Approach To Investigate Cancer Perspectives Among Residents Of Appalachian Kentucky, Courtney Martin, Lauren Hudson, Nathan L. Vanderford

Journal of Appalachian Health

Introduction: Kentucky ranks first in the U.S. in overall cancer incidence and mortality rates. Areas of the state that fall within the Appalachian Region, along Kentucky’s eastern border, experience disproportionately high rates of cancer compared to non-Appalachian counties.

Purpose: This pilot study investigates whether oral history interviews can be used to understand perspectives on cancer among residents of Appalachian Kentucky.

Methods: In 2020, participants (n = 5) who identified as being from and/or having strong connections to Appalachian Kentucky were recruited to participate in this pilot study. Participants included individuals working in cancer-related fields, oncology professionals, and those with personal …

A Better Life: Factors That Help And Hinder Entry And Retention In Mat From The Perspective Of People In Recovery, Adam D. Baus, Martha Carter, Jennifer Boyd, Erin Mcmullen, Trey Bennett, Alexandra Persily, Danielle M. Davidov, Christa Lilly

Journal of Appalachian Health

Introduction: Opioid addiction and opioid-related overdoses and deaths are serious public health problems nationally and in West Virginia, in particular. Medication-assisted treatment (MAT) is an effective yet underutilized treatment for opioid use disorder (OUD).

Purpose: Research examining factors that help individuals succeed in MAT has been conducted from provider and program perspectives, but little research has been conducted from the perspective of those in recovery.

Methods: This study, co-developed with individuals in recovery, took place in West Virginia-based MAT programs using an exploratory sequential mixed methods approach. The survey was open February through August 2021. Data were analyzed late 2021 …

Prevalence And Factors Of Self-Medication With Antibiotics In Claiborne County, Tennessee, Kimberly A. Carney, Lauren Wisnieski, Tristan Lackey, Donald Noah

Journal of Appalachian Health

Introduction: Antimicrobial resistance (AMR) is a serious concern to public health, causing an estimated 35,000 deaths annually in the U.S. Misuse of antimicrobials increases the rate of AMR. Self-medication with antibiotics (SMA) is a primary contributor to AMR that can be addressed through education. SMA has been reported at rates of 3% to 66% in the U.S. but has not been evaluated in Appalachia.¹ Low health literacy and barriers to accessing care have been correlated with SMA and are common in many areas of Appalachia.

Purpose: This study aims to assess factors associated with SMA, demographic differences in knowledge …

Cancer Screening Behaviors And Associations With Childhood Trauma, Resiliency, And Patient–Provider Relationships: Findings From An Exploratory Study Of Appalachian Cervical Cancer Survivors, Dannell Boatman, Stephenie Kennedy-Rea, Lesley Cottrell, Hannah Hazard-Jenkins

Journal of Appalachian Health

Introduction: Adverse childhood experiences (ACEs) are associated with increased cancer risk. ACEs may affect this risk in a variety of ways, including cancer screening compliance. ACEs can contribute to mistrust in the medical profession, inhibit patient­–provider relationships and cause at-risk individuals to miss critical access points to preventive services. Protective factors may play an important role in mitigating ACE-related consequences by supporting resiliency.

Purpose: This study assesses the associations between ACEs, protective factors, patient–provider relationships, stage of cancer at diagnosis, and cancer screening behaviors for West Virginia (WV) cervical cancer survivors.

Methods: WV cervical cancer survivors diagnosed between 2000 and …

Sustainability Of Beef, Dairy And Goat Production With Batiki Grass (Ischaemum Aristatum Var. Indicum) In The Dry Season In Samoa, E. M. Aregheore

IGC Proceedings (1977-2023)

Batiki grass (Ischaemum aristatum var. indicum) was introduced to Samoa from Fiji in the early 1970s to complement other existing natural or unimproved grasses and is now the most common propagated pasture grass in Samoa. The contrast between the wet and the dry seasons has a great impact on the nutritive value of batiki grass. Aregheore (2002) observed reduced growth rate, poor body condition score and low performance in steer calves and goats offered batiki as the sole diet during the dry season. This paper reports on the sustainability of beef, dairy and goat production with batiki grass …

Impact Of Community-Driven Interventions On Dietary And Physical Activity Outcomes Among A Cohort Of Adults In A Rural Appalachian County In Eastern Kentucky, 2019–2022, Heather Norman-Burgdolf, Emily M. Dewitt, Rachel Gillespie, Kathryn Cardarelli, Stacey Slone, Alison Gustafson

Dietetics and Human Nutrition Faculty Publications

Several environmental level factors exacerbate poor health outcomes in rural populations in the United States, such as lack of access to healthy food and locations to be physically active, which support healthy choices at the individual level. Thus, utilizing innovative place-based approaches in rural locations is essential to improve health outcomes. Leveraging community assets, like Cooperative Extension, is a novel strategy for implementing community-driven interventions. This prospective cohort study (n = 152), recruited in 2019 and surveyed again in 2020 and 2021, examined individual level changes in diet and physical activity in one rural Appalachian county. During this time, multiple …

A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer, Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1a (CK1a) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1a enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1a phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of …

Examining The Impact Of Teachers’ Attitudes On College Students’ Attitudes In A Mathematics Classroom, Isiaka Busari, Adeola F. Oladeji, Tolulope O. Sulaimon

Science, Technology, Engineering, and Mathematics (STEM) Education Faculty Publications

This paper discusses the relationship between teachers' attitudes and students' attitudes toward mathematics in the classroom. Through a review of more than twenty relevant pieces of literature, the paper analyzes the impact of teachers' attitudes on students' achievement, performance, confidence, and motivation in mathematics. The study concludes that positive attitudes displayed by teachers can enhance students' positive feelings toward mathematics and increase their engagement in the subject. On the other hand, negative attitudes displayed by teachers can hinder students' motivation and engagement in mathematics. The paper suggests that teacher training programs should prioritize the development of positive attitudes toward mathematics …

Modelling The Encroachment Of Farmhouse Culture On Private Village Pastures And Its Environmental Fall-Out In Northern Western Ghats, India, S. B. Nalavade, K. R. Sahasrabuddhe, A. A. Patwardhan

IGC Proceedings (1977-2023)

Tropical India harbours numerous pasturelands across small landholdings ranging up to few hectares which are covered with grass that is suitable as fodder. These grazing lands are commonly known as ‘Gairan’ in urbanised northern Western Ghats mountain tract in Western India). Such grasslands comprise about 20% of the total area of a village (Jodha, 1986), support livestock and supplement the agro-economy of the village. These pasturelands are being replaced by fenced ‘farmhouses’ of the urban elite, resulting in land use changes that caused drastic qualitative and quantitative changes in terms of area, fodder species composition and livestock they …

Translational Genomics For Alfalfa Varietal Improvement, G. D. May

IGC Proceedings (1977-2023)

Key points

1. Medicago truncatula is a model legume with available mapping, genome, and RNA, protein and metabolite profiling databases and genetically diverse populations.
2. Genomics resources developed for M. truncatula have application in the study and improvement of alfalfa making it an excellent model for this forage legume.

Decision Support For Grassland Systems In Developing Countries, P. K. Thornton

IGC Proceedings (1977-2023)

Key points

1. Information flows in complex systems are often themselves highly complex, and decision support approaches based on linear input-output processes may have only limited impact.

2. How decisions are made, and how they can be appropriately supported, is often incompletely understood, in part because of inadequate understanding of the objectives and attitudes of all the decision makers involved.

3. Much of the developing world faces daunting problems in the coming 30 years, and appropriate information could play a critical role in dealing with these.

4. System complexity, household variability, and institutional intricacies have to be embraced rather than …

Participant Engagement To Develop Report-Back Materials For Personal Air Monitoring, Patrick H. Ryan, Chris Wolfe, Allison Parsons, Cole Brokamp, Ashley Turner, Erin N. Haynes

Epidemiology and Environmental Health Faculty Publications

Background: Studies that measure environmental exposures in biological samples frequently provide participants their results. In contrast, studies using personal air monitors do not typically provide participants their monitoring results. The objective of this study was to engage adolescents who completed personal air sampling and their caregivers to develop understandable and actionable report-back documents containing the results of their personal air sampling.

Methods: Adolescents and their caregivers who previously completed personal air sampling participated in focus groups to guide the development of report-back materials. We conducted thematic analyses of focus group data to guide the design of the report-back …

A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors, Yohan Choi, Hayce Jeon, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo

UK CARES Faculty Publications

Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA- seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can …

Hpv Vaccination And Cervical Cancer Screening Promotion Among Black Individuals: Social Ecological Perspectives From Key Informants Interviews, Adebola Adegboyega, Desmennu Adeyimika, Obielodan Omoadoni, Dignan Mark

UK CARES Faculty Publications

Objectives: Rates of HPV infection and HPV-related cancers are elevated in the Black population of the US. Efforts to promote HPV vaccination and cervical cancer screening are important to reducing the cancer burden among Black populations. The purpose of this qualitative descriptive study guided by social ecological model (SEM) was to describe from the perspective of key informants, the challenges and opportunities for HPV vaccination and cervical cancer screening promotion among Black adults.

Design: Twenty-three key informants participated in individual interviews over zoom video conferencing. The sessions were audio- recorded, transcribed verbatim, and checked for accuracy prior to data analysis. …

Incorporating Environmental Impacts Into Short-Term Mine Planning: A Literature Survey, Milad Rahnema, Bahar Amirmoeini, Ali Moradi Afrapoli

Mining Engineering Faculty Publications

This paper aims to address the significant financial, environmental, and social risks posed by climate change to the mining industry, which is responsible for approximately 8% of global greenhouse gas emissions. With 70% of mining projects for the six largest mining companies located in water-stressed regions, the industry is facing increasing pressure to reduce its impact. Our study investigates the applicability of multi-objective optimization to integrate environmental impact considerations into short-term planning for mining operations. To achieve this, we have reviewed similar studies in various industries and developed an integrated planning framework that incorporates environmental considerations into production planning for …

Latexin Regulates Sex Dimorphism In Hematopoiesis Via Gender-Specific Differential Expression Of Microrna 98-3p And Thrombospondin 1, Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng-Chun Yang, Sheng Tong, Ying Liang

Markey Cancer Center Faculty Publications

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn-/- male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of micro- RNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male …

Cervical Spinal Cord Injury Leads To Injury And Altered Metabolism In The Lungs, Emily E. Huffman, Brittany E. Dong, Harrison A. Clarke, Lyndsay E. A. Young, Matthew S. Gentry, Derek B. Allison, Ramon C. Sun, Christopher M. Waters, Warren J. Alilain

Saha Cardiovascular Research Center Faculty Publications

High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury …

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Description Of Reaction And Vibrational Energetics Of Co2-Nh3interaction Using Quantum Computing Algorithms, Manh Tien Nguyen, Yueh-Lin Lee, Dominic Alfonso, Qing Shao, Yuhua Duan

Markey Cancer Center Faculty Publications

CO2 capture is critical to solving global warming. Amine-based solvents are extensively used to chemically absorb CO2. Thus, it is crucial to study the chemical absorption of CO2 by amine-based solvents to better understand and optimize CO2 capture processes. Here, we use quantum computing algorithms to quantify molecular vibrational energies and reaction pathways between CO2 and a simplified amine-based solvent model—NH3. Molecular vibrational properties are important to understanding kinetics of reactions. However, the molecule size correlates with the strength of anharmonicity effect on vibrational properties, which can be challenging to address using classical computing. Quantum computing can help enhance molecular …

Endogenous Glycoprotein Gpm6a Is Involved In Neurite Outgrowth In Rat Dorsal Root Ganglion Neurons, Gabriela I. Aparicio, Antonella León, Rocío Gutiérrez Fuster, Baylen Ravenscraft, Paula V. Monje, Camila Scorticati

Markey Cancer Center Faculty Publications

The peripheral nervous system (PNS) has a unique ability for self-repair. Dorsal root ganglion (DRG) neurons regulate the expression of different molecules, such as neurotrophins and their receptors, to promote axon regeneration after injury. However, the molecular players driving axonal regrowth need to be better defined. The membrane glycoprotein GPM6a has been described to contribute to neuronal development and structural plasticity in central-nervous-system neurons. Recent evidence indicates that GPM6a interacts with molecules from the PNS, although its role in DRG neurons remains unknown. Here, we characterized the expression of GPM6a in embryonic and adult DRGs by combining analysis of public …

Understanding Livestock Grazing Impacts: A Decision Support Tool To Develop Goal-Oriented Grazing Management Strategies, S. J. Barry, K. Guenther, G. Hayes, R. Larson, G. Nader, M. Doran

IGC Proceedings (1977-2023)

Managing grasslands in the western United States has become much more complex over the last few decades. A century ago the goal was to survive as a livestock producer, and grassland management involved using forage effectively and overcoming obstacles such as predators and shortages of water and feed. Today the successful grassland manager also needs to consider the diversity and health of the ecosystem as a whole. Livestock grazing can negatively and/or positively affect riparian areas, sensitive plants, and endangered wildlife. Since the impact on a specific factor will vary depending on the timing, intensity and class of livestock grazed, …

Grass Growth Profiles In Brittany, P. Defrance, J. M. Seuret, L. Delaby

IGC Proceedings (1977-2023)

For farmers, knowing the local grass growth profile and the possible variations between years is very helpful in managing grazing. Indeed, the comparison with herd needs and anticipated farm cover change allows decisions to be made that will maintain the cover at the desired level. This paper proposes a ten-days grass growth profile corresponding to Brittany’s different conditions of soil, climate and pasture management.

Paying For Our Keep: Grasslands Decision Support In More-Developed Countries, Andrew D. Moore

IGC Proceedings (1977-2023)

Key points

1. A survey of decision support (DS) tools in grassland agriculture illustrates the diversity of decisions supported and of delivery technologies that are used. Larger, whole-enterprise planning tools are undergoing a period where their user interfaces are being adapted to better reflect the requirements and practice of advisory users.

2. The history of use of GrassGro, a ‘versatile simulator’, is used to illustrate how versatile tools attract a diverse range of users and uses. Lessons learnt by the GrassGro team are discussed.

3. Uptake rates of DS tools in grasslands are generally lower than was expected a decade …

Optimising Financial Return From Grazing In Temperate Pastures, P. Dillon, J. R. Roche, L. Shalloo, B. Horan

IGC Proceedings (1977-2023)

Key Points

1. The increased interest in pasture-based systems of milk production in recent years has been largely generated through lower product prices and rising costs of production.

2. Pasture based systems of milk production decrease unit production costs, through lower feed and labour expenses, and reduced capital investment.

3. Systems utilising grazed pasture will be optimised in regions where pasture production potential is high, variability in seasonal pasture supply and quality is low, manufacturing milk accounts for a large proportion of total production, and where large areas of land are available at relatively low cost.

4. Pasture based systems may allow greater global …

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Decision Support For Temperate Grasslands: Challenges And Pitfalls, J. R. Donnelly, L. Salmon, R. D. H. Cohen, Zl. Liu, Xp. Xin

IGC Proceedings (1977-2023)

Key points

1. Successful adoption of decision support tools (DS tools) to address grassland management issues requires careful attention in design to ensure ease-of-use, accuracy in prediction and the flexibility to simulate actual practices.

2. DS tools must handle spatial variability and where possible include facilities for automatic sourcing of essential information for initialisation.

3. Advances in the development of DS tools will depend on resolution of scientific issues in grassland biology including investment in dedicated experiments to determine parameter values for model equations.

4. The use of mechanistic models, the integration of remote sensing technology and cooperation between research groups to develop modular …

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Grass Growth Modelling: To Increase Understanding And Aid Decision Making On-Farm, P. D. Barrett, A. S. Laidlaw

IGC Proceedings (1977-2023)

Key points

1. Crop and grass growth models have been developed over the last 50 years, or so, but general appreciation of their benefits and potential has been recognised only relatively recently. The most popular application of grass growth models has traditionally been for knowledge understanding.

2. There is growing awareness of the potential of models in decision support systems (DSS) applications to aid pasture management and grassland budgeting on dairy farms.

3. Although some models have been developed for DSS, their widespread uptake in industry has been slow; challenges still exist which need to be addressed in order to improve their precision …

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Higher Concentrations Of Microplastics In Runoff From Biosolid-Amended Croplands Than Manure-Amended Croplands, Nasrin Naderi Beni, Shahab Karimifard, John Gilley, Tiffany L. Messer, Amy Schmidt, Shannon Bartelt-Hunt

UK CARES Faculty Publications

Land-applied municipal biosolids, produced from municipal wastewater treatment sludge, contributes to microplastics contamination in agroecosystems. The impacts of biosolids on microplastic concentrations in agricultural soil have been previously investigated, however, the potential for microplastics transport from biosolid-amended croplands has not been previously quantified. In this study, manure and biosolids were applied to field plots, runoff was collected following natural precipitation events and the potential of bacterial biofilm to grow on different microplastic morphologies was investigated. Higher concentrations of microplastics were detected in runoff from plots with land-applied biosolid in comparison with manure-amended and control plots. Fibers and fragments were the …

Clic And Membrane Wound Repair Pathways Enable Pandemic Norovirus Entry And Infection, B. Vijayalakshmi Ayyar, Khalil Ettayebi, Wilhelm Salmen, Umesh C. Karandikar, Frederick H. Neill, Victoria R. Tenge, Sue E. Crawford, Erhard Bieberich, B. V. Venkataram Prasad, Robert L. Atmar, Mary K. Estes

Markey Cancer Center Faculty Publications

Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell …