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Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu Jan 2023

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

Nebraska Center for Virology: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …


Integration Of Transcriptome-Wide Association Study With Neuronal Dysfunction Assays Provides Functional Genomics Evidence For Parkinson’S Disease Genes, Akash Tarkunde, Katy Fan Zhu, Alma Perez, Megan Mair, Justin Moore, Joshua M Shulman, Ismael Al-Ramahi, Juan Botas Jan 2023

Integration Of Transcriptome-Wide Association Study With Neuronal Dysfunction Assays Provides Functional Genomics Evidence For Parkinson’S Disease Genes, Akash Tarkunde, Katy Fan Zhu, Alma Perez, Megan Mair, Justin Moore, Joshua M Shulman, Ismael Al-Ramahi, Juan Botas

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) have markedly advanced our understanding of the genetics of Parkinson's disease (PD), but they currently do not account for the full heritability of PD. In many cases it is difficult to unambiguously identify a specific gene within each locus because GWAS does not provide functional information on the identified candidate loci. Here we present an integrative approach that combines transcriptome-wide association study (TWAS) with high-throughput neuronal dysfunction analyses in Drosophila to discover and validate candidate PD genes. We identified 160 candidate genes whose misexpression is associated with PD risk via TWAS. Candidates were validated using orthogonal …


Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu Jan 2023

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

Nebraska Center for Virology: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …


Inhibition Of Colorectal Cancer Tumorigenesis By Ursolic Acid And Doxorubicin Is Mediated By Targeting The Akt Signaling Pathway And Activating The Hippo Signaling Pathway, Dan Hu, Ruo Yu Meng, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Soo Mi Kim Jan 2023

Inhibition Of Colorectal Cancer Tumorigenesis By Ursolic Acid And Doxorubicin Is Mediated By Targeting The Akt Signaling Pathway And Activating The Hippo Signaling Pathway, Dan Hu, Ruo Yu Meng, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Soo Mi Kim

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product‑derived and chemotherapy agents including curcumin combined with 5‑fluorouracil, resveratrol combined with cisplatin and epigallocatechin‑3‑gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The Akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of UA and DOX on the cell proliferation, apoptosis, migration …


Monitoring And Modulating Diet And Gut Microbes To Enhance Response And Reduce Toxicity To Cancer Treatment, Anne Knisely, Yongwoo David Seo, Jennifer A Wargo, Manoj Chelvanambi Jan 2023

Monitoring And Modulating Diet And Gut Microbes To Enhance Response And Reduce Toxicity To Cancer Treatment, Anne Knisely, Yongwoo David Seo, Jennifer A Wargo, Manoj Chelvanambi

Faculty, Staff and Student Publications

The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can …


Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar Jan 2023

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …


Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar Jan 2023

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …


Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar Jan 2023

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …


Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar Jan 2023

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …


A Data-Driven Approach To Construct A Molecular Map Of Trypanosoma Cruzi To Identify Drugs And Vaccine Targets, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal Jan 2023

A Data-Driven Approach To Construct A Molecular Map Of Trypanosoma Cruzi To Identify Drugs And Vaccine Targets, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during their phylogenesis. In this work, we have assembled an interactive network of the complex relations that occur between molecules within T. cruzi. An expert curation strategy was combined with a text-mining approach to screen 10,234 full-length research articles and over 200,000 abstracts relevant to T. cruzi. We obtained a scale-free network consisting of 1055 nodes …


Engineered Protac-Cid Systems For Mammalian Inducible Gene Regulation, Victor Paredes, Hongzhi Zeng, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Anika Patel, Megan S Liu, Zheng Sun, Xue Gao Jan 2023

Engineered Protac-Cid Systems For Mammalian Inducible Gene Regulation, Victor Paredes, Hongzhi Zeng, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Anika Patel, Megan S Liu, Zheng Sun, Xue Gao

Faculty, Staff and Students Publications

Gene regulation via chemically induced dimerization (CID) is useful for biomedical research. However, the number, type, versatility, and in vivo applications of CID tools remain limited. Here, we demonstrate the development of proteolysis-targeting chimera-based scalable CID (PROTAC-CID) platforms by systematically engineering the available PROTAC systems for inducible gene regulation and gene editing. Further, we show orthogonal PROTAC-CIDs that can fine-tune gene expression at gradient levels or multiplex biological signals with different logic gating operations. Coupling the PROTAC-CID platform with genetic circuits, we achieve digitally inducible expression of DNA recombinases, base- and prime-editors for transient genome manipulation. Finally, we package a …


Gut Microbiota And Microbiota-Derived Metabolites Promotes Endometriosis, Chandni Talwar, Satwikreddy Putluri, Chandrasekhar R Ambati, Michael A Lint, Andrew L Kau, Christina L Stallings, Ramakrishna Kommagani Jan 2023

Gut Microbiota And Microbiota-Derived Metabolites Promotes Endometriosis, Chandni Talwar, Satwikreddy Putluri, Chandrasekhar R Ambati, Michael A Lint, Andrew L Kau, Christina L Stallings, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct …


Gut Microbiota And Microbiota-Derived Metabolites Promotes Endometriosis, Chandni Talwar, Satwikreddy Putluri, Chandrasekhar R Ambati, Michael A Lint, Andrew L Kau, Christina L Stallings, Ramakrishna Kommagani Jan 2023

Gut Microbiota And Microbiota-Derived Metabolites Promotes Endometriosis, Chandni Talwar, Satwikreddy Putluri, Chandrasekhar R Ambati, Michael A Lint, Andrew L Kau, Christina L Stallings, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct …


Tmem161b Regulates Cerebral Cortical Gyration, Sonic Hedgehog Signaling, And Ciliary Structure In The Developing Central Nervous System, David Exposito-Alonso, Norma K Hylton, Grace H Hwang, Jennifer E Neil, Nicole Dominado, Rosie K Bunton-Stasyshyn, Janet H T Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G Beck, Rebecca C Yeh, Aoi Otani, Xuyu Qian, Ellen M Degennaro, Fowzan S Alkuraya, Sateesh Maddirevula, Gregory D Cascino, Caterina Giannini, Undiagnosed Diseases Network, Lindsay C Burrage, Jill A Rosenfield, Shamika Ketkar, Gary D Clark, Carlos Bacino, Richard A Lewis, Rosalind A Segal, J Fernando Bazan, Kelly A Smith, Jeffrey A Golden, Ginam Cho, Christopher A Walsh Jan 2023

Tmem161b Regulates Cerebral Cortical Gyration, Sonic Hedgehog Signaling, And Ciliary Structure In The Developing Central Nervous System, David Exposito-Alonso, Norma K Hylton, Grace H Hwang, Jennifer E Neil, Nicole Dominado, Rosie K Bunton-Stasyshyn, Janet H T Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G Beck, Rebecca C Yeh, Aoi Otani, Xuyu Qian, Ellen M Degennaro, Fowzan S Alkuraya, Sateesh Maddirevula, Gregory D Cascino, Caterina Giannini, Undiagnosed Diseases Network, Lindsay C Burrage, Jill A Rosenfield, Shamika Ketkar, Gary D Clark, Carlos Bacino, Richard A Lewis, Rosalind A Segal, J Fernando Bazan, Kelly A Smith, Jeffrey A Golden, Ginam Cho, Christopher A Walsh

Faculty, Staff and Students Publications

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B, which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret …


Recent Advances In Understanding Of Pathogenesis Of Alcohol-Associated Liver Disease, Xiaoqin Wu, Xiude Fan, Tatsunori Miyata, Adam Kim, Christina K Cajigas-Du Ross, Emily Huang, Rakesh Arya, Jianguo Wu, Laura E Nagy Jan 2023

Recent Advances In Understanding Of Pathogenesis Of Alcohol-Associated Liver Disease, Xiaoqin Wu, Xiude Fan, Tatsunori Miyata, Adam Kim, Christina K Cajigas-Du Ross, Emily Huang, Rakesh Arya, Jianguo Wu, Laura E Nagy

Faculty, Staff and Student Publications

Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis …


Cbx5 Loss Drives Egfr Inhibitor Resistance And Results In Therapeutically Actionable Vulnerabilities In Lung Cancer, Suresh Bugide, Yvonne J K Edwards, Romi Gupta, Michael R Green, Narendra Wajapeyee Jan 2023

Cbx5 Loss Drives Egfr Inhibitor Resistance And Results In Therapeutically Actionable Vulnerabilities In Lung Cancer, Suresh Bugide, Yvonne J K Edwards, Romi Gupta, Michael R Green, Narendra Wajapeyee

Faculty, Staff and Student Publications

Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFRi) are approved for treating EGFR-mutant lung adenocarcinoma (LUAD), emergence of acquired resistance limits their clinical benefits. Several mechanisms for acquired resistance to EGFRi in LUAD have been identified; however, the molecular basis for this resistance remains unknown in ~30% of LUAD. Chromatin and DNA modifiers and their regulators play important roles in determining response to anticancer therapies. Therefore, to identify nongenetic mechanisms of EGFRi resistance in LUAD, we performed an epigenome-wide shRNA screen targeting 363 human epigenetic regulator genes. This screen identified loss of the transcriptional repressor chromobox homolog 5 …


Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Bo Wei, Philip L Lorenzi, Richard Lehner, Kai Sun Jan 2023

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Bo Wei, Philip L Lorenzi, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …


Genetics And Pathogenesis Of Parkinson's Syndrome, Matthew Cykowski, Joshua M Shulman Jan 2023

Genetics And Pathogenesis Of Parkinson's Syndrome, Matthew Cykowski, Joshua M Shulman

Faculty, Staff and Students Publications

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops a virtually unique form of Parkinson's syndrome. Clinical manifestations consist of variable motor and nonmotor features, and myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central and peripheral nervous systems, the distribution varies and other pathologies commonly modify PD or trigger similar manifestations. Nearly all PD is genetically influenced. More than 100 genes or genetic loci have been identified, and most cases likely arise from interactions among many common …


A Novel Defined Tlr3 Agonist As An Effective Vaccine Adjuvant, Kwang Hyun Ko, Seung Bin Cha, Seung-Hwan Lee, Hyun Shik Bae, Chul Soo Ham, Dong-Ho Kim Jan 2023

A Novel Defined Tlr3 Agonist As An Effective Vaccine Adjuvant, Kwang Hyun Ko, Seung Bin Cha, Seung-Hwan Lee, Hyun Shik Bae, Chul Soo Ham, Dong-Ho Kim

Faculty, Staff and Student Publications

Synthetic double-stranded RNA analogs recognized by Toll-like receptor 3 (TLR3) are an attractive adjuvant candidate for vaccines, especially against intracellular pathogens or tumors, because of their ability to enhance T cell and antibody responses. Although poly(I:C) is a representative dsRNA with potent adjuvanticity, its clinical application has been limited due to heterogeneous molecular size, inconsistent activity, poor stability, and toxicity. To overcome these limitations, we developed a novel dsRNA-based TLR3 agonist named NexaVant (NVT) by using PCR-coupled bidirectional in vitro transcription. Agarose gel electrophoresis and reverse phase-HPLC analysis demonstrated that NVT is a single 275-kDa homogeneous molecule. NVT appears to …


Integrating Semaglutide Into Obesity Management - A Primary Care Perspective, Janine V. Kyrillos, Neil S. Skolnik, Bhasha Mukhopadhyay, Nicholas Pennings Jan 2023

Integrating Semaglutide Into Obesity Management - A Primary Care Perspective, Janine V. Kyrillos, Neil S. Skolnik, Bhasha Mukhopadhyay, Nicholas Pennings

Jefferson Hospital Staff Papers and Presentations

This final article in the supplement aims to summarize a clinical approach for weight management geared toward primary care practitioners, offering practical advice about how to integrate weight management into day-to-day practice. To achieve long-term successful weight loss, a comprehensive multimodal approach is recommended, focusing on both lifestyle modification and appropriate use of therapy. Once-weekly subcutaneous semaglutide 2.4 mg is a novel treatment that can be used as an adjunct to lifestyle modification for the management of overweight and obesity. Key considerations are presented to support its optimal administration in conjunction with lifestyle modification, with a focus on assessing suitability …


The Nfib/Carm1 Partnership Is A Driver In Preclinical Models Of Small Cell Lung Cancer, Guozhen Gao, Simone Hausmann, Natasha M Flores, Ana Morales Benitez, Jianjun Shen, Maria D Person, Donghang Cheng, Yue Lu, Bin Liu, Pawel K Mazur, Mark T Bedford Jan 2023

The Nfib/Carm1 Partnership Is A Driver In Preclinical Models Of Small Cell Lung Cancer, Guozhen Gao, Simone Hausmann, Natasha M Flores, Ana Morales Benitez, Jianjun Shen, Maria D Person, Donghang Cheng, Yue Lu, Bin Liu, Pawel K Mazur, Mark T Bedford

Faculty, Staff and Student Publications

The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator. Biochemical studies reveal that tripartite motif 29 (TRIM29) is an effector molecule for methylated NFIB. Importantly, NFIB harbors both oncogenic and metastatic activities, and is often overexpressed in small cell lung cancer (SCLC). Here, we explore the possibility that CARM1 methylation of NFIB is important for its transforming activity. Using a SCLC mouse model, we show …


Digital Health Interventions To Improve Adolescent Hpv Vaccination: A Systematic Review, Christine Markham Jan 2023

Digital Health Interventions To Improve Adolescent Hpv Vaccination: A Systematic Review, Christine Markham

Faculty, Staff and Student Publications

Digital technologies are being increasingly utilized in healthcare to provide pertinent and timely information for primary prevention, such as vaccination. This study aimed to conduct a systematic review to describe and assess current digital health interventions to promote HPV vaccination among adolescents and parents of adolescents, and to recommend directions for future interventions of this kind. Using appropriate medical subject headings and keywords, we searched multiple databases to identify relevant studies published in English between 1 January 2017 and 31 July 2022. We screened and selected eligible studies for inclusion in the final analysis. We reviewed a total of 24 …


Fluorescence Angiography With Dual Fluorescence For The Early Detection And Longitudinal Quantitation Of Vascular Leakage In Retinopathy, Abigail S Hackam, Midhat H Abdulreda Jan 2023

Fluorescence Angiography With Dual Fluorescence For The Early Detection And Longitudinal Quantitation Of Vascular Leakage In Retinopathy, Abigail S Hackam, Midhat H Abdulreda

Faculty, Staff and Students Publications

BACKGROUND: Diabetic retinopathy (DR) afflicts more than 93 million people worldwide and is a leading cause of vision loss in working adults. While DR therapies are available, early DR development may go undetected without treatment due to the lack of sufficiently sensitive tools. Therefore, early detection is critically important to enable efficient treatment before progression to vision-threatening complications. A major clinical manifestation of early DR is retinal vascular leakage that may progress from diffuse to more localized focal leakage, leading to increased retinal thickness and diabetic macular edema (DME). In preclinical research, a hallmark of DR in mouse models is …


Svhound: Detection Of Regions That Harbor Yet Undetected Structural Variation, Jeffrey Rogers, Arndt Von Haeseler, Fritz J Sedlazeck Jan 2023

Svhound: Detection Of Regions That Harbor Yet Undetected Structural Variation, Jeffrey Rogers, Arndt Von Haeseler, Fritz J Sedlazeck

Faculty, Staff and Students Publications

BACKGROUND: Recent population studies are ever growing in number of samples to investigate the diversity of a population or species. These studies reveal new polymorphism that lead to important insights into the mechanisms of evolution, but are also important for the interpretation of these variations. Nevertheless, while the full catalog of variations across entire species remains unknown, we can predict which regions harbor additional not yet detected variations and investigate their properties, thereby enhancing the analysis for potentially missed variants.

RESULTS: To achieve this we developed SVhound ( https://github.com/lfpaulin/SVhound ), which based on a population level SVs dataset can predict …


Investigating Stigma During The Early Stages Of A Pandemic Through The Lens Of Covid-19, Zach Thornton, Bethany Hodge, Sheridan Langford Jan 2023

Investigating Stigma During The Early Stages Of A Pandemic Through The Lens Of Covid-19, Zach Thornton, Bethany Hodge, Sheridan Langford

The University of Louisville Journal of Respiratory Infections

Background: Individuals face stigma associated with numerous health conditions. Stigma can arise rapidly during the early spread of a new disease, adding to the burden felt by those affected. COVID-19 can be used as an example to study stigma during the early phases of a pandemic. This narrative review is a descriptive analysis that tracks the ways in which COVID-19 stigma was discussed in the scholarly literature during the first year of the pandemic to understand how stigma was viewed in the context of a rapidly spreading pandemic.

Methods: PubMed was used as a non-exhaustive sample of the literature. Searches …


Pgc-1Α Senses The Cbc Of Pre-Mrna To Dictate The Fate Of Promoter-Proximally Paused Rnapii, Xavier Rambout, Hana Cho, Roméo Blanc, Qing Lyu, Joseph M Miano, Joe V Chakkalakal, Geoffrey M Nelson, Hari K Yalamanchili, Karen Adelman, Lynne E Maquat Jan 2023

Pgc-1Α Senses The Cbc Of Pre-Mrna To Dictate The Fate Of Promoter-Proximally Paused Rnapii, Xavier Rambout, Hana Cho, Roméo Blanc, Qing Lyu, Joseph M Miano, Joe V Chakkalakal, Geoffrey M Nelson, Hari K Yalamanchili, Karen Adelman, Lynne E Maquat

Children’s Nutrition Research Center Staff Publications

PGC-1α is well established as a metazoan transcriptional coactivator of cellular adaptation in response to stress. However, the mechanisms by which PGC-1α activates gene transcription are incompletely understood. Here, we report that PGC-1α serves as a scaffold protein that physically and functionally connects the DNA-binding protein estrogen-related receptor α (ERRα), cap-binding protein 80 (CBP80), and Mediator to overcome promoter-proximal pausing of RNAPII and transcriptionally activate stress-response genes. We show that PGC-1α promotes pausing release in a two-arm mechanism (1) by recruiting the positive transcription elongation factor b (P-TEFb) and (2) by outcompeting the premature transcription termination complex Integrator. Using mice …


Control Of Craniofacial Development By The Collagen Receptor, Discoidin Domain Receptor 2, Fatma F Mohamed, Chunxi Ge, Shawn A Hallett, Alec C Bancroft, Randy T Cowling, Abdul-Aziz Binrayes, Benjamin Levi, Vesa M Kaartinen, Renny T Franceschi Jan 2023

Control Of Craniofacial Development By The Collagen Receptor, Discoidin Domain Receptor 2, Fatma F Mohamed, Chunxi Ge, Shawn A Hallett, Alec C Bancroft, Randy T Cowling, Abdul-Aziz Binrayes, Benjamin Levi, Vesa M Kaartinen, Renny T Franceschi

Faculty, Staff and Student Publications

Development of the craniofacial skeleton requires interactions between progenitor cells and the collagen-rich extracellular matrix (ECM). The mediators of these interactions are not well-defined. Mutations in the discoidin domain receptor 2 gene (DDR2), which encodes a non-integrin collagen receptor, are associated with human craniofacial abnormalities, such as midface hypoplasia and open fontanels. However, the exact role of this gene in craniofacial morphogenesis is not known. As will be shown, Ddr2-deficient mice exhibit defects in craniofacial bones including impaired calvarial growth and frontal suture formation, cranial base hypoplasia due to aberrant chondrogenesis and delayed ossification at growth plate …


The “Evolving” Role Of Intravascular Imaging In Myocardial Infarction With Nonobstructive Coronary Arteries, D L Fischman, Vaikom S. Mahadevan, Eric R. Bates Jan 2023

The “Evolving” Role Of Intravascular Imaging In Myocardial Infarction With Nonobstructive Coronary Arteries, D L Fischman, Vaikom S. Mahadevan, Eric R. Bates

Division of Internal Medicine Faculty Papers & Presentations

No abstract provided.


Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu Jan 2023

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …


Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen Jan 2023

Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen

Faculty, Staff and Students Publications

No abstract provided.