Digital Commons Network^™

International Society For Extracellular Vesicles Workshop Quantitatevs: Multiscale Analyses, From Bulk To Single Extracellular Vesicle, Manuela Basso, Alessandro Gori, Caterina Nardella, Mari Palviainen, Marija Holcar, Ioannis Sotiropoulos, Sylwia Bobis-Wozowicz, Vito G D'Agostino, Elena Casarotto, Yari Ciani, Shiro Suetsugu, Alice Gualerzi, Lorena Martin-Jaular, Daniela Boselli, Anna Kashkanova, Pietro Parisse, Lien Lippens, Martina Pagliuca, Martin Blessing, Roberto Frigerio, Thibaut Fourniols, Ana Meliciano, Anna Fietta, Paolo Vincenzo Fioretti, Karolina Soroczyńska, Silvia Picciolini, Amanda Salviano-Silva, Paolo Bergese, Davide Zocco, Marcella Chiari, Guido Jenster, Levi Waldron, Aleksandar Milosavljevic, John Nolan, Marco P Monopoli, Kenneth W Witwer, Benedetta Bussolati, Dolores Di Vizio, Juan Falcon Perez, Metka Lenassi, Marina Cretich, Francesca Demichelis

Faculty, Staff and Students Publications

The “QuantitatEVs: multiscale analyses, from bulk to single vesicle” workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV‐associated molecular components and EV biophysical features, which are considered the core of EV‐associated biomarker discovery and validation for their clinical translation. The in‐person‐only workshop was held in Trento, Italy, from January 31st to February 2nd, 2023, and continued in Milan on February 3rd with “Next …

Effects And Plasma Proteomic Analysis Of Glp-1ra Versus Cpa/Ee, In Combination With Metformin, On Overweight Pcos Women: A Randomized Controlled Trial, Mingyu Liao, Xing Li, Hao Zhang, Ling Zhou, Liu Shi, Weixin Li, Rufei Shen, Guiliang Peng, Huan Zhao, Jiaqing Shao, Xiujie Wang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.

METHODS: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. …

Mfgm-Enriched Whey Displays Antiviral Activity Against Common Pediatric Viruses, Evelien Kramer, Ketki Patil, Vassilis Triantis, Jan A H Bastiaans, Michela Mazzon, Sasirekha Ramani, Tim T Lambers

Faculty, Staff and Students Publications

BACKGROUND: Among the most common mucosal viral infections in infants are rotavirus, one of the main causes of severe gastroenteritis in infants and children up to 5 years, and respiratory syncytial virus (RSV), one of the leading causes of lower respiratory tract infections. Both human milk and bovine milk derived factors may provide protection against mucosal viral infections. More recently, a similar activity of milk derived proteins was suggested for SARS-CoV-2. The goal of the current study was to test antiviral activity of the bovine milkfat globule membrane (MFGM) against rotavirus, RSV and SARS-CoV-2 and to further characterize MFGM-enriched whey …

Select Gut Microbiota Impede Rotavirus Vaccine Efficacy, Vu L Ngo, Yanling Wang, Yadong Wang, Zhenda Shi, Robert Britton, Jun Zou, Sasirekha Ramani, Baoming Jiang, Andrew T Gewirtz

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.

METHODS: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge.

RESULTS: SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV …

Folate Regulation Of Planar Cell Polarity Pathway And F-Actin Through Folate Receptor Alpha, Xiao Han, Xuanye Cao, Robert M Cabrera, Paula Andrea Pimienta Ramirez, Ying Linda Lin, Bogdan J Wlodarczyk, Cuilian Zhang, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, Folic acid (FA) and 5-methyltetrahydrofolate(5mTHF), at concentration of 5uM, 500nM, 50nM and folate free, respectively. Mouse embryonic fibroblasts (MEFs) were treated with different folates continuously for three passages and cell proliferation and F-actin was monitored. We determined that compared to 5mTHF, FA showed stronger effects on promoting cell proliferation and …

Developing A Pathway To Clinical Trials For Cacna1a-Related Epilepsies: A Patient Organization Perspective, Pangkong M Fox, Sunitha Malepati, Lisa Manaster, Elsa Rossignol, Jeffrey L Noebels

Faculty, Staff and Students Publications

CACNA1A-related disorders are rare neurodevelopmental disorders linked to variants in the CACNA1A gene. This gene encodes the α1 subunit of the P/Q-type calcium channel Cav2.1, which is globally expressed in the brain and crucial for fast synaptic neurotransmission. The broad spectrum of CACNA1A-related neurological disorders includes developmental and epileptic encephalopathies, familial hemiplegic migraine type 1, episodic ataxia type 2, spinocerebellar ataxia type 6, together with unclassified presentations with developmental delay, ataxia, intellectual disability, autism spectrum disorder, and language impairment. The severity of each disorder is also highly variable. The spectrum of CACNA1A-related seizures is broad across both loss-of-function and gain-of-function …

Combined Bioinformatic And Splicing Analysis Of Likely Benign Intronic And Synonymous Variants Reveals Evidence For Pathogenicity, Owen R Hirschi, Stephanie A Felker, Surya P Rednam, Kelly L Vallance, D Williams Parsons, Angshumoy Roy, Gregory M Cooper, Sharon E Plon

Faculty, Staff and Students Publications

PURPOSE: Clinical variant analysis pipelines likely have poor sensitivity to the effects on splicing from variants beyond 10 to 20 bases of exon-intron boundaries. Here, we demonstrate the value of SpliceAI to inform curation of rare variants previously classified as benign/likely benign (B/LB) under current guidelines.

METHODS: Exome sequencing data from 576 pediatric cancer patients enrolled in the Texas KidsCanSeq study were filtered for intronic or synonymous variants absent from population databases, predicted to alter splicing via SpliceAI (>0.20), and scored >10 by combined annotation-dependent depletion. Rare synonymous or intronic B/LB variants in 61 genes submitted to ClinVar were …

Attitudes Toward Persons With Disabilities And Disability Awareness Of University Students Providing Healthcare, Canan Ertemoğlu Öksüz, Özlem Kanber Uzun, Şahi Nur Kalkışım, Nihat Burak Zihni

Makara Journal of Health Research

Background: This study aims to determine the attitudes and disability awareness of university students who provide health services to persons with disabilities.

Methods: This study included 291 volunteer students studying at the Vocational School of Health Services, Karadeniz Technical University (KTU), and conducting clinical practice at KTU Farabi Hospital. A sociodemographic form was used to determine the individual characteristics of the students included in this study, and the Attitudes toward Disabled Persons Scale (ATDP) was applied to determine their attitudes toward persons with disabilities.

Results: The students’ average ATDP score was 61.75 ± 12.34. Statistically significant differences …

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Lidocaine Induces Apoptosis In Head And Neck Squamous Cell Carcinoma Through Activation Of Bitter Taste Receptor T2r14, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, Sahil Muthuswami, April Park, Derek B Mcmahon, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

Microcalcification Crystallography As A Potential Marker Of Dcis Recurrence, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, Sahil Muthuswami, April Park, Derek B Mcmahon, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

Stabilizing Vimentin Phosphorylation Inhibits Stem-Like Cell Properties And Metastasis Of Hybrid Epithelial/Mesenchymal Carcinomas, Nick A Kuburich, Petra Den Hollander, Maria Castaneda, Mika Pietilä, Ximing Tang, Harsh Batra, Francisco Martínez-Peña, Tanvi H Visal, Tieling Zhou, Breanna R Demestichas, Ritesh V Dontula, Jojo Y Liu, Joanna Joyce Maddela, Reethi S Padmanabhan, Lan Thi Hanh Phi, Matthew J Rosolen, Thiru Sabapathy, Dhiraj Kumar, Filippo G Giancotti, Luke L Lairson, Maria Gabriela Raso, Rama Soundararajan, Sendurai A Mani

Faculty, Staff and Student Publications

Epithelial-mesenchymal transition (EMT) empowers epithelial cells with mesenchymal and stem-like attributes, facilitating metastasis, a leading cause of cancer-related mortality. Hybrid epithelial-mesenchymal (E/M) cells, retaining both epithelial and mesenchymal traits, exhibit heightened metastatic potential and stemness. The mesenchymal intermediate filament, vimentin, is upregulated during EMT, enhancing the resilience and invasiveness of carcinoma cells. The phosphorylation of vimentin is critical to its structure and function. Here, we identify that stabilizing vimentin phosphorylation at serine 56 induces multinucleation, specifically in hybrid E/M cells with stemness properties but not epithelial or mesenchymal cells. Cancer stem-like cells are especially susceptible to vimentin-induced multinucleation relative to …

Co-Transmitting Interneurons In The Mouse Olfactory Bulb Regulate Olfactory Detection And Discrimination, Ariel M Lyons-Warren, Evelyne K Tantry, Elizabeth H Moss, Mikhail Y Kochukov, Benjamin D W Belfort, Joshua Ortiz-Guzman, Zachary Freyberg, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons …

Pivotal Trial Of A Deep-Learning-Based Retinal Biomarker (Reti-Cvd) In The Prediction Of Cardiovascular Disease: Data From Cmerc-Hi, Chan Joo Lee, Tyler Hyungtaek Rim, Hyun Goo Kang, Joseph Keunhong Yi, Geunyoung Lee, Marco Yu, Soo-Hyun Park, Jin-Taek Hwang, Yih-Chung Tham, Tien Yin Wong, Ching-Yu Cheng, Dong Wook Kim, Sung Soo Kim, Sungha Park

The Brown Foundation: Institute of Molecular Medicine

Objective: The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk.

Materials and methods: In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) …

Navigating Transitions: Cranialsacral Therapy, Occupational Therapy And Neuroregulation Strategies For Adjusting To A New Home, Carol J. Reshan

Journal of Transformative Touch

Report of working with a hyper-vigilant 9-year-old male with difficulty handling a transition to a new home. CST and sensory processing enhancement were utilized to help develop neuroregulation, enabling self-awareness, self-regulation, and personally directed life skills for maintaining a safe and alert state.

Ints6 And The Integrator Phosphatase Module Tune The Efficiency Of Select Premature Transcription Termination Events, Rina Fujiwara, Si-Nan Zhai, Dongming Liang, Aayushi P Shah, Matthew Tracey, Xu-Kai Ma, Christopher J Fields, María Saraí Mendoza-Figueroa, Michele C Meline, Deirdre C Tatomer, Li Yang, Jeremy E Wilusz

Children’s Nutrition Research Center Staff Publications

The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset of Drosophila protein-coding genes, although having no effect on snRNAs or attenuation of other loci. Over-expressed IntS6 titrates protein phosphatase 2A (PP2A) subunits, thereby only affecting gene loci where phosphatase activity is necessary for Integrator function. IntS6 functions analogous to a PP2A regulatory …

Current Biomedical Applications Of 3d-Printed Hydrogels, Allan John R Barcena, Kashish Dhal, Parimal Patel, Prashanth Ravi, Suprateek Kundu, Karthik Tappa

Faculty, Staff and Student Publications

Three-dimensional (3D) printing, also known as additive manufacturing, has revolutionized the production of physical 3D objects by transforming computer-aided design models into layered structures, eliminating the need for traditional molding or machining techniques. In recent years, hydrogels have emerged as an ideal 3D printing feedstock material for the fabrication of hydrated constructs that replicate the extracellular matrix found in endogenous tissues. Hydrogels have seen significant advancements since their first use as contact lenses in the biomedical field. These advancements have led to the development of complex 3D-printed structures that include a wide variety of organic and inorganic materials, cells, and …

Mir-410 Is A Key Regulator Of Epithelial-To-Mesenchymal Transition With Biphasic Role In Prostate Cancer, Diana M Asante, Amritha Sreekumar, Sandip Nathani, Tae Jin Lee, Ashok Sharma, Nikhil Patel, Matthew N Simmons, Sharanjot Saini

Faculty, Staff and Student Publications

The molecular basis of prostate cancer (PCa) progression from the primary disease to metastatic castration-resistant prostate cancer (CRPC) followed by therapy-induced neuroendocrine prostate cancer is not fully understood. In this study, we elucidate the role of miR-410, a little-studied microRNA located on chromosome 14q32.31 within the DLK1-DIO3 cluster, in PCa. miR-410 expression analyses in primary and metastatic PCa tissues and cell lines show that its levels are decreased in initial stages and increased in advanced PCa. Functional studies were performed in a series of PCa cell lines. In LNCaP cells, miR-410 overexpression led to decreases in cellular viability, proliferation, invasiveness, …

The Involvement Of Hepatic Cytochrome P450s In The Cytotoxicity Of Lapatinib, Si Chen, Xilin Li, Yuxi Li, Xiaobo He, Matthew Bryant, Xuan Qin, Feng Li, Ji-Eun Seo, Xiaoqing Guo, Nan Mei, Lei Guo

Faculty, Staff and Students Publications

Lapatinib, an oral tyrosine kinase inhibitor used as a first-line treatment for HER2-positive breast cancer, has been reported to be associated with hepatotoxicity; however, the underlying mechanisms remain unclear. In this study, we report that lapatinib causes cytotoxicity in multiple types of hepatic cells, including primary human hepatocytes, HepaRG cells, and HepG2 cells. A 24-h treatment with lapatinib induced cell cycle disturbances, apoptosis, and DNA damage, and decreased the protein levels of topoisomerase in HepG2 cells. We investigated the role of cytochrome P450 (CYP)-mediated metabolism in lapatinib-induced cytotoxicity using our previously established HepG2 cell lines, which express each of 14 …

Effects Of Episodic Food Insecurity On Psychological And Physiological Responses In African American Women With Obesity (Responses): Protocol For A Longitudinal Observational Cohort Study, Candice A. Myers, Robbie A. Beyl, Daniel S. Hsia, Melissa N. Harris, Isabella J. Reed, Danielle D. Eliser, Lauren Bagneris, John W. Apolzan

School of Public Health Faculty Publications

Background; Food insecurity is a risk factor for multiple chronic diseases, including obesity. Importantly, both food insecurity and obesity are more prevalent in African American women than in other groups. Furthermore, food insecurity is considered a cyclic phenomenon, with episodes of food adequacy (ie, enough food to eat) and food shortage (ie, not enough food to eat). More research is needed to better understand why food insecurity is linked to obesity, including acknowledging the episodic nature of food insecurity as a stressor and identifying underlying mechanisms. Objective; The objective of this study is to investigate the episodic nature of food …

The Potential For Development Of Clinically Relevant Microbial Resistance To Rifaximin-Α: A Narrative Review, Herbert L Dupont

Faculty, Staff and Student Publications

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. …

Bacterial Outer Membrane Vesicles Provide An Alternative Pathway For Trafficking Of Escherichia Coli O157 Type Iii Secreted Effectors To Epithelial Cells, Natalie Sirisaengtaksin, Eloise J O'Donoghue, Sara Jabbari, Andrew J Roe, Anne Marie Krachler

Faculty, Staff and Student Publications

Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Cp-673451, A Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces Apoptosis In Opisthorchis Viverrini-Associated Cholangiocarcinoma Via Nrf2 Suppression And Enhanced Ros, Jinchutha Duangdara, Boonyakorn Boonsri, Apinya Sayinta, Kittiya Supradit, Pakpoom Thintharua, Supeecha Kumkate, Chinnawut Suriyonplengsaeng, Noppadol Larbcharoensub, Somkit Mingphruedhi, Narongsak Rungsakulkij, Paramin Muangkaew, Pongsatorn Tangtawee, Watoo Vassanasiri, Wikran Suragul, Tavan Janvilisri, Rutaiwan Tohtong, David O Bates, Kanokpan Wongprasert

Faculty, Staff and Students Publications

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) play essential roles in promoting cholangiocarcinoma (CCA) cell survival by mediating paracrine crosstalk between tumor and cancer-associated fibroblasts (CAFs), indicating the potential of PDGFR as a target for CCA treatment. Clinical trials evaluating PDGFR inhibitors for CCA treatment have shown limited efficacy. Furthermore, little is known about the role of PDGF/PDGFR expression and the mechanism underlying PDGFR inhibitors in CCA related to Opisthorchis viverrini (OV). Therefore, we examined the effect of PDGFR inhibitors in OV-related CCA cells and investigated the molecular mechanism involved. We found that the PDGF and PDGFR mRNAs were …

Mgmt Function Determines The Differential Response Of Atr Inhibitors With Dna-Damaging Agents In Glioma Stem Cells For Gbm Therapy, Vincent W S Leong, Sabbir Khan, Pratibha Sharma, Shaofang Wu, Riya R Thomas, Xiaolong Li, Sanjay K Singh, Frederick F Lang, Alfred W K Yung, Dimpy Koul

Faculty, Staff and Student Publications

BACKGROUND: The most prevalent cancer treatments cause cell death through DNA damage. However, DNA damage response (DDR) repair pathways, initiated by tumor cells, can withstand the effects of anticancer drugs, providing justification for combining DDR inhibitors with DNA-damaging anticancer treatments.

METHODS: Cell viability assays were performed with CellTiter-Glo assay. DNA damage was evaluated using Western blotting analysis. RNA-seq and single-cell level expression were used to identify the DDR signatures. In vivo, studies were conducted in mice to determine the effect of ATris on TMZ sensitization.

RESULTS: We found a subpopulation of glioma sphere-forming cells (GSCs) with substantial synergism with temozolomide …

Interlaboratory Comparison Of Pseudomonas Aeruginosa Phage Susceptibility Testing, Krupa Parmar, Lauren Komarow, Damon W Ellison, Andrey A Filippov, Mikeljon P Nikolich, Joseph R Fackler, Martin Lee, Anjna Nair, Priyesh Agrawal, Pranita D Tamma, Maria Souli, Scott R Evans, Kerryl E Greenwood-Quaintance, Scott A Cunningham, Robin Patel, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay. Four Pseudomonas aeruginosa phages: PaWRA01ø11 (EPa11), PaWRA01ø39 (EPa39), PaWRA02ø83 (EPa83), PaWRA02ø87 (EPa87), and a cocktail of all four phages were tested against 145 P. aeruginosa isolates. Comparisons were made within measurements at the two sites performing the liquid assay and between these …

Interleukin-17-Mediated Protective Cytokine Signaling Against Degeneration Of The Retinal Pigment Epithelium, Yan Chen, Sarah E Bounds, Xiang Ma, James Regun Karmoker, Yin Liu, Jian-Xing Ma, Jiyang Cai

Faculty, Staff and Student Publications

Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor …

Rotavirus-Mediated Dgat1 Degradation: A Pathophysiological Mechanism Of Viral-Induced Malabsorptive Diarrhea, Zheng Liu, Hunter Smith, Jeanette M Criglar, Antonio J Valentin, Umesh Karandikar, Xi-Lei Zeng, Mary K Estes, Sue E Crawford

Faculty, Staff and Students Publications

Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by …

Mirna-211 Maintains Metabolic Homeostasis In Medulloblastoma Through Its Target Gene Long-Chain Acyl-Coa Synthetase 4, Menglang Yuan, Iqbal Mahmud, Keisuke Katsushima, Kandarp Joshi, Olivier Saulnier, Rudramani Pokhrel, Bongyong Lee, Wathsala Liyanage, Haritha Kunhiraman, Stacie Stapleton, Ignacio Gonzalez-Gomez, Rangaramanujam M Kannan, Tanja Eisemann, Elayaraja Kolanthai, Sudipta Seal, Timothy J Garrett, Saed Abbasi, Kimberly Bockley, Justin Hanes, Prem Chapagain, George Jallo, Robert J Wechsler-Reya, Michael D Taylor, Charles G Eberhart, Animesh Ray, Ranjan J Perera

Faculty, Staff and Students Publications

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected …