Medicine and Health Sciences Commons^™

Impact Of Diabetes On The Gut And Salivary Iga Microbiomes, Eric L Brown, Heather T Essigmann, Kristi L Hoffman, Noah W Palm, Sarah M Gunter, Joel M Sederstrom, Joseph F Petrosino, Goo Jun, David Aguilar, William B Perkison, Craig L Hanis, Herbert L Dupont

Journal Articles

Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA; therefore, a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health …

Rna Nanoparticles And Method Of Use Thereof, Peixuan Guo, Hui Li, Wei Luo

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to an artificial RNA nanostructure and method of use thereof. In particular, the presently-disclosed subject matter relates to RNA nanoparticles and RNA dendrimers, and methods of disease diagnosis and treatments using the RNA nanostructure and RNA dendrimers.

Gene Selection For Optimal Prediction Of Cell Position In Tissues From Single-Cell Transcriptomics Data., Jovan Tanevski, Thin Nguyen, Buu Truong, Nikos Karaiskos, Mehmet Eren Ahsen, Xinyu Zhang, Chang Shu, Ke Xu, Xiaoyu Liang, Ying Hu, Hoang Vv Pham, Li Xiaomei, Thuc D Le, Adi L Tarca, Gaurav Bhatti, Roberto Romero, Nestoras Karathanasis, Phillipe Loher, Yang Chen, Zhengqing Ouyang, Disheng Mao, Yuping Zhang, Maryam Zand, Jianhua Ruan, Christoph Hafemeister, Peng Qiu, Duc Tran, Tin Nguyen, Attila Gabor, Thomas Yu, Justin Guinney, Enrico Glaab, Roland Krause, Peter Banda, Gustavo Stolovitzky, Nikolaus Rajewsky, Julio Saez-Rodriguez, Pablo Meyer

Computational Medicine Center Faculty Papers

Single-cell RNA-sequencing (scRNAseq) technologies are rapidly evolving. Although very informative, in standard scRNAseq experiments, the spatial organization of the cells in the tissue of origin is lost. Conversely, spatial RNA-seq technologies designed to maintain cell localization have limited throughput and gene coverage. Mapping scRNAseq to genes with spatial information increases coverage while providing spatial location. However, methods to perform such mapping have not yet been benchmarked. To fill this gap, we organized the DREAM Single-Cell Transcriptomics challenge focused on the spatial reconstruction of cells from the Drosophila embryo from scRNAseq data, leveraging as silver standard, genes with in situ hybridization …

Rna Nanoparticle For Treatment Of Gastric Cancer, Peixuan Guo, Daxiang Cui, Dan Shu, Yi Shu, Chunlei Zhang

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer.

Long Noncoding Rna H19x Is A Key Mediator Of Tgf-Β-Driven Fibrosi, Elena Pachera, Shervin Assassi, Gloria A Salazar, Mara Stellato, Florian Renoux, Adam Wunderlin, Przemyslaw Blyszczuk, Robert Lafyatis, Fina Kurreeman, Jeska De Vries-Bouwstra, Tobias Messemaker, Carol A Feghali-Bostwick, Gerhard Rogler, Wouter T Van Haaften, Gerard Dijkstra, Fiona Oakley, Maurizio Calcagni, Janine Schniering, Britta Maurer, Jörg Hw Distler, Gabriela Kania, Mojca Frank-Bertoncelj, Oliver Distler

Journal Articles

TGF-β is a master regulator of fibrosis, driving the differentiation of fibroblasts into apoptosis-resistant myofibroblasts and sustaining the production of extracellular matrix (ECM) components. Here, we identified the nuclear long noncoding RNA (lncRNA) H19X as a master regulator of TGF-β-driven tissue fibrosis. H19X was consistently upregulated in a wide variety of human fibrotic tissues and diseases and was strongly induced by TGF-β, particularly in fibroblasts and fibroblast-related cells. Functional experiments following H19X silencing revealed that H19X was an obligatory factor for TGF-β-induced ECM synthesis as well as differentiation and survival of ECM-producing myofibroblasts. We showed that H19X regulates DDIT4L gene …

Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki

Computational Medicine Center Faculty Papers

Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 …

Atrx Deletion In Neurons Leads To Sexually Dimorphic Dysregulation Of Mir-137 And Spatial Learning And Memory Deficits., Renee J. Tamming, Vanessa Dumeaux, Yan Jiang, Sarfraz Shafiq, Luana Langlois, Jacob Ellegood, Lily R. Qiu, Jason P. Lerch, Nathalie G. Bérubé

Paediatrics Publications

ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the …

Cold-Inducible Rna Binding Protein (Cirp) Impedes Proliferation And Inflammation In The Pymt Mouse Model For Breast Cancer, Daniel Albino Lujan

Biomedical Sciences ETDs

RNA binding proteins (RBPs) regulate gene expression by controlling mRNA export, translation, and stability. When altered, some RBPs allow cancer cells to grow, survive, and metastasize. Cold-inducible RNA binding protein (CIRP) is overexpressed in a subset of breast cancers, induces proliferation in breast cancer cell lines, and inhibits apoptosis. We generated a transgenic mouse model overexpressing human CIRP in the mammary epithelium to ask if it plays a role in mammary gland development. We also assessed the effects of CIRP on breast tumorigenesis using breeding crosses with the PyMT mouse model for breast cancer. CIRP decreased proliferation at the lactational …

Rna Nanoparticles For Brain Tumor Treatment, Peixuan Guo, Carlo M. Croce, Tae Jin Lee, Farzin Haque, Hui Li

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to an artificial RNA nanostructure molecule and method to treat brain tumor in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure containing a multiple branched RNA nanoparticle, a brain tumor targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanostructure composition to treat brain tumor in a subject having or at risk of having brain tumor.

Structural Biology Of The Enterovirus Replication-Linked 5'-Cloverleaf Rna And Associated Virus Proteins, Steven M. Pascal, Ravindranath Garimella, Meghan S. Warden, Komala Ponniah

Chemistry & Biochemistry Faculty Publications

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5′ end of the strand is an approximately 90-nucleotide self-complementary region called the 5′ cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural …

Aerosol And Surface Contamination Of Sars-Cov-2 Observed In Quarantine And Isolation Care, Joshua L. Santarpia, Danielle N. Rivera, Vicki L. Herrera, M. Jane Morwitzer, Hannah M. Creager, George W. Santarpia, Kevin K. Crown, David Brett-Major, Elizabeth R. Schnaubelt, M. Jana Broadhurst, James V. Lawler, St. Patrick Reid, John Lowe

Journal Articles: Epidemiology

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in late 2019, and its resulting coronavirus disease, COVID-19, was declared a pandemic by the World Health Organization on March 11, 2020. The rapid global spread of COVID-19 represents perhaps the most significant public health emergency in a century. As the pandemic progressed, a continued paucity of evidence on routes of SARS-CoV-2 transmission has resulted in shifting infection prevention and control guidelines between classically-defined airborne and droplet precautions. During the initial isolation of 13 individuals with COVID-19 at the University of Nebraska Medical Center, we collected air …

Diagnosing Mild Traumatic Brain Injury Using Saliva Rna Compared To Cognitive And Balance Testing, Steven D. Hicks, Cayce Onks, Raymond Y. Kim, Kevin J. Zhen, Jayson Loeffert, Andrea C. Loeffert, Robert P. Olympia, Gregory Fedochak, Samantha Devita, Aakanksha Rangnekar, John Leddy, Mohammad N. Haider, Zofia Gagnon, Callan D. Mcloughlin, Matthew Badia, Jason Randall, Miguel Madeira, Aaron M. Yengo-Kahn, Justin Wenzel, Matthew Heller, Hallie Zwibel, Aaron Roberts, Samantha Johnson, Chuck Monteith, Michael N. Dretsch, Thomas R. Campbell, Rebekah Mannix, Christopher Neville, Frank Middleton

Rehabilitation Sciences Faculty Publications

BACKGROUND: Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance.

METHODS: This case‐control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled …