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Full-Text Articles in Genetics and Genomics

A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy Dec 2022

A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy

Nebraska Center for Virology: Faculty Publications

Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in …


Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current E, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder Dec 2022

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current E, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

Nebraska Center for Virology: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …


Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille Dec 2022

Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille

Nebraska Center for Virology: Faculty Publications

Moraxella bovis (M. bovis) is regarded as a causative agent of infectious bovine keratoconjunctivitis (IBK), the most common ocular disease of cattle. Recently, whole genome sequencing identified the presence of two distinct genotypes within M. bovis that differ in chromosome content, potential virulence factors, as well as prophage and plasmid profiles. It is unclear if the genotypes equally associate with IBK or if one is more likely to be isolated from IBK lesions. We utilized 39 strains of M. bovis that had previously undergone whole genome sequencing and genotype classification to determine the utility of matrix-assisted laser desorption/ionization …


Isolation And Characterization Of Chi-Like Salmonella Bacteriophages Infecting Two Salmonella Enterica Serovars, Typhimurium And Enteritidis, Addisu D. Teklemariam, Mona G. Alharbi, Rashad R. Al-Hindi, Ibrahim Alotibi, Abdullah A. Aljaddawi, Sheren A. Azhari, Ahmed Esmael Dec 2022

Isolation And Characterization Of Chi-Like Salmonella Bacteriophages Infecting Two Salmonella Enterica Serovars, Typhimurium And Enteritidis, Addisu D. Teklemariam, Mona G. Alharbi, Rashad R. Al-Hindi, Ibrahim Alotibi, Abdullah A. Aljaddawi, Sheren A. Azhari, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Salmonella enterica Serovar Typhimurium and Salmonella enterica Serovar Enteritidis are well-known pathogens that cause foodborne diseases in humans. The emergence of antibiotic-resistant Salmonella serovars has caused serious public health problems worldwide. In this study, two lysogenic phages, STP11 and SEP13, were isolated from a wastewater treatment plant in Jeddah, KSA. Transmission electron microscopic images revealed that both phages are new members of the genus “Chivirus” within the family Siphoviridae. Both STP11 and SEP13 had a lysis time of 90 min with burst sizes of 176 and 170 PFU/cell, respectively. The two phages were thermostable (0 C …


Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz Dec 2022

Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz

Journal Articles

No abstract provided.


A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang Nov 2022

A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Epstein‐Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two‐step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play …


Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin Nov 2022

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …


Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro Nov 2022

Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro

Nebraska Center for Virology: Faculty Publications

Interleukin-33 (IL-33), which promotes M2 macrophage development, may influence the control of viruses, such as Theiler’s Murine Encephalomyelitis Virus (TMEV) that infect macrophages. Because Interferon Regulatory Factor-3 (IRF3) is also critical to control of TMEV infection in macrophages, information on the relationship between IL-33 and IRF3 is important. Thus, RAW264.7 Lucia murine macrophage lineage cells with an endogenous IRF3-ISRE promoter driving secreted luciferase and IRF3KO RAW Lucia, a subline deficient in IRF3, were challenged with TMEV. After the challenge, considerable TMEV RNA detected at 18 and 24 h in RAW cells was significantly elevated in IRF3KO RAW cells. TMEV induction …


A Single Amino Acid Substitution In Porcine Reproductive And Respiratory Syndrome Virus Glycoprotein 2 Significantly Impairs Its Infectivity In Macrophages, Jayeshbhai Chaudhari, Raquel Arruda Leme, Kassandra Durazo-Martinez, Sarah Vitosh-Sillman, Aspen M. Workman, Hiep Vu Nov 2022

A Single Amino Acid Substitution In Porcine Reproductive And Respiratory Syndrome Virus Glycoprotein 2 Significantly Impairs Its Infectivity In Macrophages, Jayeshbhai Chaudhari, Raquel Arruda Leme, Kassandra Durazo-Martinez, Sarah Vitosh-Sillman, Aspen M. Workman, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted tropism for macrophages and CD163 is a key receptor for infection. In this study, the PRRSV strain NCV1 was passaged on MARC-145 cells for 95 passages, and two plaque-clones (C1 and C2) were randomly selected for further analysis. The C1 virus nearly lost the ability to infect porcine alveolar macrophages (PAMs), as well as porcine kidney cells expressing porcine CD163 (PK15-pCD163), while the C2 virus replicates well in these two cell types. Pretreatment of MARC-145 cells with an anti-CD163 antibody nearly blocked C1 virus infection, indicating that the virus still …


Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro Nov 2022

Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro

Nebraska Center for Virology: Faculty Publications

Interleukin-33 (IL-33), which promotes M2 macrophage development, may influence the control of viruses, such as Theiler’s Murine Encephalomyelitis Virus (TMEV) that infect macrophages. Because Interferon Regulatory Factor-3 (IRF3) is also critical to control of TMEV infection in macrophages, information on the relationship between IL-33 and IRF3 is important. Thus, RAW264.7 Lucia murine macrophage lineage cells with an endogenous IRF3-ISRE promoter driving secreted luciferase and IRF3KO RAW Lucia, a subline deficient in IRF3, were challenged with TMEV. After the challenge, considerable TMEV RNA detected at 18 and 24 h in RAW cells was significantly elevated in IRF3KO RAW cells. TMEV induction …


Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis Nov 2022

Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

Nebraska Center for Virology: Faculty Publications

Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that …


The “Big Six”: Hidden Emerging Foodborne Bacterial Pathogens, Mona G. Alharbi, Rashad R. Al-Hindi, Ahmed Esmael, Ibrahim A. Alotibi, Sheren A. Azhari, Mazen S. Alseghayer, Addisu D. Teklemariam Nov 2022

The “Big Six”: Hidden Emerging Foodborne Bacterial Pathogens, Mona G. Alharbi, Rashad R. Al-Hindi, Ahmed Esmael, Ibrahim A. Alotibi, Sheren A. Azhari, Mazen S. Alseghayer, Addisu D. Teklemariam

Nebraska Center for Virology: Faculty Publications

Non-O157 Shiga toxin-producing Escherichia coli (STEC) are emerging serogroups that often result in diseases ranging from diarrhea to severe hemorrhagic colitis in humans. The most common non-O157 STEC are O26, O45, O103, O111, O121, and O145. These serogroups are known by the name “big six” because they cause severe illness and death in humans and the United States Department of Agriculture declared these serogroups as food contaminants. The lack of fast and efficient diagnostic methods exacerbates the public impact of the disease caused by these serogroups. Numerous outbreaks have been reported globally and most of these outbreaks were caused by …


Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen Nov 2022

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …


Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan Oct 2022

Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …


Proteômica Plasmática Quantitativa De Pacientes Sobreviventes E Não Sobreviventes De Covid-19 Internados No Hospital Revela Potenciais Biomarcadores Prognósticos E Alvos Terapêuticos, D C. Flora, A D. Valle, H Abs Pereira, T F. Garbieri, L. T. Grizzo, T J. Dionisio, A L. Leite, D Mc Rosa, C F. Santos, M Ar Buzalaf Oct 2022

Proteômica Plasmática Quantitativa De Pacientes Sobreviventes E Não Sobreviventes De Covid-19 Internados No Hospital Revela Potenciais Biomarcadores Prognósticos E Alvos Terapêuticos, D C. Flora, A D. Valle, H Abs Pereira, T F. Garbieri, L. T. Grizzo, T J. Dionisio, A L. Leite, D Mc Rosa, C F. Santos, M Ar Buzalaf

Nebraska Center for Virology: Faculty Publications

O desenvolvimento de novas abordagens que permitam a avaliação precoce de quais casos de COVID-19 provavelmente se tornarão críticos e a descoberta de novos alvos terapêuticos são importantes. Neste estudo de coorte, foi avaliado o perfil proteômico e laboratorial do plasma de 163 pacientes internados no Hospital Estadual de Bauru (Bauru, SP, Brasil) entre 4 de maio e 4 de julho de 2020, que foram diagnosticados com COVID-19 por RT-PCR a partir de amostras de swab nasofaríngeo amostras. Amostras de plasma foram coletadas na admissão para análises laboratoriais de rotina e análise proteôomica quantitativa shotgun livre de marcadores. De acordo …


Heterogeneity In The Prevalence Of Premature Hypertension Among Asian American Populations Compared With White Individuals: A National Health Interview Survey Study, Sina Kianoush, Mahmoud Al Rifai, Anwar T. Merchant, Xiaoming Jia, Zainab Samad, Aneil Bhalla, Ayesha Khan, Dongshan Zhu, Salim S. Virani Sep 2022

Heterogeneity In The Prevalence Of Premature Hypertension Among Asian American Populations Compared With White Individuals: A National Health Interview Survey Study, Sina Kianoush, Mahmoud Al Rifai, Anwar T. Merchant, Xiaoming Jia, Zainab Samad, Aneil Bhalla, Ayesha Khan, Dongshan Zhu, Salim S. Virani

Section of Cardiology

Background: Differences in prevalence of risk factors such as hypertension may explain heterogeneity in cardiovascular risk across Asian American populations.
Methods: We used National Health Interview Survey (NHIS) data from 2006 to 2018 among White, Chinese, Asian Indian, Filipino, and 'other Asians' (Japanese, Korean, and Vietnamese). Unadjusted and adjusted odds ratios (aOR) with 95% confidence intervals were reported using logistic regression models for the association between race and self-reported premature hypertension (age old). Models were adjusted for sex, education, body mass index, smoking status, diabetes, and coronary heart disease.
Results: We studied 99,864 participants with history of hypertension (mean age, …


Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli Sep 2022

Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The prevalence of liver disease is steadily increasing, coupled with the limited availability of therapeutic treatments. Recent literature points to metabolic reprogramming as a key feature of liver failure. Hence, we sought to uncover the metabolic pathways and mechanisms associated with liver disease and acute liver failure. We generated patient-specific genome scale metabolic models by integrating RNA-seq data from patient liver samples with a generalized human metabolic model. Flux balance analysis simulations showed a distinct separation of non-alcohol associated and alcohol-associated disease states. Our analysis suggests that the alcohol associated liver has an increased flux through nucleotide and glycerophospholipid metabolic …


Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S Regalado, Shaine A Morris, Alan C Braverman, Ellen M Hostetler, Julie De Backer, Ruosha Li, Reed E Pyeritz, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz Aug 2022

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S Regalado, Shaine A Morris, Alan C Braverman, Ellen M Hostetler, Julie De Backer, Ruosha Li, Reed E Pyeritz, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz

Journal Articles

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …


Association Between The Baseline Gene Expression Profile In Periapical Granuloma And Periapical Wound Healing After Surgical Endodontic Treatment, Muhammad Adeel Ahmed, Fizza Nazim, Khalid Ahmed, Muhammad Furqan Bari, Abdulaziz Abdulwahed, Ahmed A. Almokhatieb, Yaseen Alalvi, Tariq Abduljabbar, Muhammad Nouman Mughal, Syed Hani Abidi Aug 2022

Association Between The Baseline Gene Expression Profile In Periapical Granuloma And Periapical Wound Healing After Surgical Endodontic Treatment, Muhammad Adeel Ahmed, Fizza Nazim, Khalid Ahmed, Muhammad Furqan Bari, Abdulaziz Abdulwahed, Ahmed A. Almokhatieb, Yaseen Alalvi, Tariq Abduljabbar, Muhammad Nouman Mughal, Syed Hani Abidi

Department of Biological & Biomedical Sciences

In this study, we have investigated the association between the baseline gene expression profile in periapical granuloma and periapical wound healing after surgical endodontic treatment. Twenty-seven patients aged between 15 and 57 years underwent periapical surgery. The retrieved periapical tissue sample was used for mRNA expression analysis of COL1A1, VTN, ITGA5, IL-4, TNF, ANGPT, VEGFA, and CTGF. All patients were recalled after 6 and 12 months for periapical healing evaluation. Healing was then correlated with baseline gene expression. Healing was observed in 15 patients at the end of 6 months, which increased to 21 patients after 12 months. Six patients …


The Sars-Cov-2 Differential Genomic Adaptation In Response To Varying Uvindex Reveals Potential Genomic Resources For Better Covid-19 Diagnosis And Prevention, Naveed Iqbal, Muhammad Rafiq, Masooma Ali, Sanaullah Tareen, Maqsood Ahmad, Faheem Nawaz, Sumair Khan, Rida Riaz, Ting Yang, Ambrin Fatima Aug 2022

The Sars-Cov-2 Differential Genomic Adaptation In Response To Varying Uvindex Reveals Potential Genomic Resources For Better Covid-19 Diagnosis And Prevention, Naveed Iqbal, Muhammad Rafiq, Masooma Ali, Sanaullah Tareen, Maqsood Ahmad, Faheem Nawaz, Sumair Khan, Rida Riaz, Ting Yang, Ambrin Fatima

Department of Biological & Biomedical Sciences

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from …


Host And Gut Microbial Tryptophan Metabolism And Type 2 Diabetes: An Integrative Analysis Of Host Genetics, Diet, Gut Microbiome And Circulating Metabolites In Cohort Studies, Qibin Qi, Jun Li, Bing Yu, Jee-Young Moon, Jin C Chai, Jordi Merino, Jie Hu, Miguel Ruiz-Canela, Casey Rebholz, Zheng Wang, Mykhaylo Usyk, Guo-Chong Chen, Bianca C Porneala, Wenshuang Wang, Ngoc Quynh Nguyen, Elena V Feofanova, Megan L Grove, Thomas J Wang, Robert E Gerszten, Josée Dupuis, Jordi Salas-Salvadó, Wei Bao, David L Perkins, Martha L Daviglus, Bharat Thyagarajan, Jianwen Cai, Tao Wang, Joann E Manson, Miguel A Martínez-González, Elizabeth Selvin, Kathryn M Rexrode, Clary B Clish, Frank B Hu, James B Meigs, Rob Knight, Robert D Burk, Eric Boerwinkle, Robert C Kaplan Jun 2022

Host And Gut Microbial Tryptophan Metabolism And Type 2 Diabetes: An Integrative Analysis Of Host Genetics, Diet, Gut Microbiome And Circulating Metabolites In Cohort Studies, Qibin Qi, Jun Li, Bing Yu, Jee-Young Moon, Jin C Chai, Jordi Merino, Jie Hu, Miguel Ruiz-Canela, Casey Rebholz, Zheng Wang, Mykhaylo Usyk, Guo-Chong Chen, Bianca C Porneala, Wenshuang Wang, Ngoc Quynh Nguyen, Elena V Feofanova, Megan L Grove, Thomas J Wang, Robert E Gerszten, Josée Dupuis, Jordi Salas-Salvadó, Wei Bao, David L Perkins, Martha L Daviglus, Bharat Thyagarajan, Jianwen Cai, Tao Wang, Joann E Manson, Miguel A Martínez-González, Elizabeth Selvin, Kathryn M Rexrode, Clary B Clish, Frank B Hu, James B Meigs, Rob Knight, Robert D Burk, Eric Boerwinkle, Robert C Kaplan

Journal Articles

OBJECTIVE: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.

METHOD: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.

RESULTS: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with …


Detoxification Role Of Metabolic Glutathione S-Transferase (Gst) Genes In Blood Lead Concentrations Of Jamaican Children With And Without Autism Spectrum Disorder, Mohammad H Rahbar, Maureen Samms-Vaughan, Sori Kim, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland May 2022

Detoxification Role Of Metabolic Glutathione S-Transferase (Gst) Genes In Blood Lead Concentrations Of Jamaican Children With And Without Autism Spectrum Disorder, Mohammad H Rahbar, Maureen Samms-Vaughan, Sori Kim, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Journal Articles

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2−8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child’s parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.


When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha May 2022

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

University Scholar Projects

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …


Spontaneous Coronary Artery Dissection Is Infrequent In Individuals With Heritable Thoracic Aortic Disease Despite Partially Shared Genetic Susceptibility, Andrea M Murad, Hannah L Hill, Yu Wang, Michael Ghannam, Min-Lee Yang, Norma L Pugh, Federico M Asch, Whitney Hornsby, Anisa Driscoll, Jennifer Mcnamara, Cristen J Willer, Ellen S Regalado, Dianna M Milewicz, Kim A Eagle, Santhi K Ganesh May 2022

Spontaneous Coronary Artery Dissection Is Infrequent In Individuals With Heritable Thoracic Aortic Disease Despite Partially Shared Genetic Susceptibility, Andrea M Murad, Hannah L Hill, Yu Wang, Michael Ghannam, Min-Lee Yang, Norma L Pugh, Federico M Asch, Whitney Hornsby, Anisa Driscoll, Jennifer Mcnamara, Cristen J Willer, Ellen S Regalado, Dianna M Milewicz, Kim A Eagle, Santhi K Ganesh

Journal Articles

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), …


Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver Jan 2022

Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells …


The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz Jan 2022

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Nebraska Center for Virology: Faculty Publications

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …


Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver Jan 2022

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the …


Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu Jan 2022

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …


Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz Jan 2022

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …


Factors Impacting Genomic Testing Rates Among Epithelial Ovarian Cancer Patients Across A Large Community-Based Healthcare System, Nicole M. Kretzer, Christopher J. Darus, Nancy Biery, Roshanthi Weerasinghe, Grace Li, Ann Vita, Shwetha Pindikuri, Amy S. Parrish, Charles W Drescher, Fernanda B. Musa Jan 2022

Factors Impacting Genomic Testing Rates Among Epithelial Ovarian Cancer Patients Across A Large Community-Based Healthcare System, Nicole M. Kretzer, Christopher J. Darus, Nancy Biery, Roshanthi Weerasinghe, Grace Li, Ann Vita, Shwetha Pindikuri, Amy S. Parrish, Charles W Drescher, Fernanda B. Musa

All Podium Presentations

Background: Epithelial ovarian cancer (EOC) accounts for the highest mortality of all gynecological cancers. NCCN guidelines recommend germline and somatic testing for all women with invasive EOC. Despite this recommendation, there is a large diversity in the types of testing patients receive even within a single healthcare system. Reported data of genetic testing for epithelial ovarian cancer (EOC) patients is largely based on patients treated at academic medical centers or patients who participate in clinical trials.

Purpose: This study sought to determine the rates of germline and somatic testing for epithelial ovarian cancer patients and identify factors that impact testing …