Digital Commons Network^™

How Carvedilol Does Not Activate Β2-Adrenoceptors, Robert J. Lefkowitz, Howard A. Rockman, Paul J. Shim, Samuel Liu, Seungkirl Ahn, Biswaranjan Pani, Sudarshan Rajagopal, Sudha K. Shenoy, Michel Bouvier, Jeffrey L. Benovic, Stephen B. Liggett, Robert R. Ruffolo, Michael R. Bristow, Milton Packer

Department of Biochemistry and Molecular Biology Faculty Papers

No abstract provided.

Delineating The Interplay Between Oncogenic Pathways And Immunity In Anaplastic Wilms Tumors, Xiaoping Su, Xiaofan Lu, Sehrish Khan Bazai, Linda Dainese, Arnauld Verschuur, Benoit Dumont, Roger Mouawad, Li Xu, Wenxuan Cheng, Fangrong Yan, Sabine Irtan, Véronique Lindner, Catherine Paillard, Yves Le Bouc, Aurore Coulomb, Gabriel G Malouf

Faculty, Staff and Student Publications

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell …

Attempts To Understand Oral Mucositis In Head And Neck Cancer Patients Through Omics Studies: A Narrative Review, Erin Marie D San Valentin, Kim-Anh Do, Sai-Ching J Yeung, Cielito C Reyes-Gibby

Faculty, Staff and Student Publications

Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host …

Cannabinoids In Periodontology: Where Are We Now?, Yésica Carmona Rendón, Hernán Santiago Garzón, Bruno Bueno-Silva, Roger M Arce, Lina Janeth Suárez

Faculty, Staff and Student Publications

Introduction: Cannabinoids are a well-documented treatment modality for various immune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease, Crohn's disease, arthritis, multiple sclerosis, and a range of neurodegenerative conditions. However, limited information is available regarding the therapeutic potential of cannabinoids in treating periodontal disease.

Objective: The objective of this study is to analyze the current evidence on the antibacterial and immunomodulatory effects of cannabis and its role in the healing and regeneration processes within periodontal tissues.

Results: This review discusses the potential role of cannabinoids in restoring periodontal tissue homeostasis.

Conclusions: The examination of the endocannabinoid system and the …

Loss Of The Methylarginine Reader Function Of Snd1 Confers Resistance To Hepatocellular Carcinoma, Tanner Wright, Yalong Wang, Sabrina A Stratton, Manu Sebastian, Bin Liu, David G Johnson, Mark T Bedford

Faculty, Staff and Student Publications

Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that 'reads' methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two genetically engineered SND1 mouse models, an Snd1 knockout (Snd1 KO) and an Snd1 Tudor domain-mutated (Snd1 KI) mouse, whose mutant SND1 can …

Autogenous Reproduction By Ornithodoros Turicata (Ixodida: Argasidae) Females And Vertical Transmission Of The Tick-Borne Pathogen Borrelia Turicatae (Spirochaetales: Borreliaceae), Serhii Filatov, Aparna Krishnavajhala, Job E Lopez

Faculty, Staff and Students Publications

Ornithodoros turicata is a vector of relapsing fever spirochetes in North America and transmits Borrelia turicatae to a variety of vertebrate hosts. The remarkably long lifespan of O. turicata and its ability to maintain spirochetes horizontally (between life stages) and vertically (to progeny) promote the perpetuation of B. turicatae in nature. Nevertheless, the reproductive biology of O. turicata is poorly understood. In this report, we collected ticks from a park within a neighborhood of Austin, TX. They were reared to adulthood, and male ticks were individually housed with females. We observed autogenous reproduction, which is the ability to produce eggs …

Data-Driven Multiscale Model Of Macaque Auditory Thalamocortical Circuits Reproduces In Vivo Dynamics, Salvador Dura-Bernal, Erica Y Griffith, Annamaria Barczak, Monica N O'Connell, Tammy Mcginnis, Joao V S Moreira, Charles E Schroeder, William W Lytton, Peter Lakatos, Samuel A Neymotin

Faculty, Staff and Student Publications

We developed a detailed model of macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator and NetPyNE tool. The A1 model simulates a cortical column with over 12,000 neurons and 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, and connectivity across six cortical layers. It is reciprocally connected to the MGB thalamus, which includes interneurons and core and matrix-layer-specific projections to A1. The model simulates multiscale measures, including physiological firing rates, local field potentials (LFPs), current source densities (CSDs), and electroencephalography (EEG) signals. Laminar CSD patterns, …

A Heritable Iron Memory Enables Decision-Making In Escherichia Coli, Souvik Bhattacharyya, Nabin Bhattarai, Dylan M Pfannenstiel, Brady Wilkins, Abhyudai Singh, Rasika M Harshey

Faculty, Staff and Student Publications

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when Escherichia coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This “iron” memory preexists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, which tracks with …

Celastrol Restricts Experimental Periodontitis Related Alveolar Bone Loss By Suppressing Inflammatory Cytokine Response, Ahmet Altin, Meltem Zi̇hni̇ Korkmaz, Mehtap Atak, Tolga Mercantepe, Hülya Kiliç Yilmaz

BioMedicine

Introduction: Periodontitis is a common chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. The host defense mechanisms are responsible for inflamatuar and destructive reactions in periodontitis. Celastrol is one of the most promising components of the plant in Eastern and Southern China that has a long history of use in traditional medicine for the treatment of inflammatory conditions. Aim: The aim of this animal study was to inspect the preventive or restrictive effects of celastrol on periodontitis-related inflammatory host response and alveolar bone loss. Methods: 24 male Sprague Dawley rats were randomly assigned into …

Hematological Biomarkers Of Troponin, Neutrophil-To-Lymphocyte Ratio, And Monocyte-Tolymphocyte Ratio Serve As Effective Predictive Indicators Of High-Risk Mortality In Acute, Bryan Gervais De Liyis, Angela Faustine Ciaves, Marwa Humaira Intizam, Pierre Joshua Jusuf, I Made Junior Rina Artha

BioMedicine

Background: Assessing high-risk mortality in acute coronary syndrome (ACS) patients, encompassing ST-Elevation Myocardial Infarction (STEMI), Non-ST-Elevation Myocardial Infarction (NSTEMI), and Unstable Angina Pectoris (UAP), is crucial. However, the prognostic significance of hematological parameters in predicting high-risk mortality in ACS patients remains uncertain despite advancements in ACS research. Aim: The aim was to investigate prognostic significance of hematological parameters troponin, Creatine Kinase-MB (CKMB), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Basophil-to-Lymphocyte Ratio (BLR), and Eosinophil-to-Lymphocyte Ratio (ELR) levels in predicting high-risk mortality in ACS patients. Methods: In this retrospective observational study, data from medical records of 115 patients with …

Efficacy Of Hmj-38, A New Quinazolinone Analogue, Against The Gemcitabine-Resistant Mia-Paca-2 Pancreatic Cancer Cells, Mann-Jen Hour, Fuu‑ Jen Tsai, I-Lu Lai, Je-Wei Tsao, Jo-Hua Chiang, Yu-Jen Chiu, Hsing-Fang Lu, Yu‑ Ning Juan, Jai-Sing Yang, Shih-Chang Tsai

BioMedicine

Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIAGR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50, or 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced …

Chemical Composition, Mineral Profile, Anti-Bacterial, And Wound Healing Properties Of Snail Slime Of Helix Aspersa Müller, Marouane Aouji, Amine Rkhaila, Bouchra Bouhaddioui, Malak Zirari, Hala Harifi, Youness Taboz, Lalla Aicha Lrhorfi, Rachid Bengueddour

BioMedicine

Mucus is a substance made by snails that serves a variety of purposes and is increasingly employed in the medical and cosmetic industries. It includes bioactive compounds with a range of biological characteristics that could be useful in the treatment of particular issues. This study assessed the wound-healing efficiency, antibacterial activity, chemical and mineral composition of Helix aspersa Müller slime. Inductively Coupled Argon Plasma Atomic Emission Spectrometry (ICP-OES) was used for mineral analysis, while Gas chromatography coupled to mass spectrometry (GC-MS) analysis was used for chemical characterization. The findings showed that the H. aspersa Müller slime had inhibitory activity on …

Mutation Patterns Of Integrase Gene Affect Antiretroviral Resistance In Various Non-B Subtypes Of Human Immunodeficiency Virus Type-1 And Their Implications For Patients’ Therapy, Fauzia Andrini Djojosugito, Arfianti Arfianti, Rudi , Wisaksana, Agnes Rengga Indrati

BioMedicine

Although primary integrase strand transfer inhibitor resistance mutations are currently uncommon, the increasing use of integrase strand transfer inhibitor as a key component of the first, second and third-line antiretroviral regimens suggests that the prevalence of integrase drug resistance mutations will likely increase. The rise of several polymorphic mutations and natural polymorphisms also affects the level of susceptibility of human immunodeficiency virus (HIV) type-1 to integrase strand transfer inhibitor. The considerable variability among the various subtypes of human immunodeficiency virus type-1 may contribute to differences in integrase mutations associated with integrase strand transfer inhibitors. Notably, non-B subtypes of HIV type-1 …

Rcc2 Promotes Prostate Cancer Cell Proliferation And Migration Through Hh/Gli1 Signaling Pathway And Cancer Stem-Like Cells, Shenghan Wang, Zhentao Lei, Wei Liu, Jie Xiong, Yuqiang Shi, Lin Yang, Qiang Gao, Kai Le, Bao Zhang

Faculty, Staff and Student Publications

BACKGROUND: Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.

METHODS: The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were …

Single-Cell Multiomics Of The Human Retina Reveals Hierarchical Transcription Factor Collaboration In Mediating Cell Type-Specific Effects Of Genetic Variants On Gene Regulation, Jun Wang, Xuesen Cheng, Qingnan Liang, Leah A Owen, Jiaxiong Lu, Yiqiao Zheng, Meng Wang, Shiming Chen, Margaret M Deangelis, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

BACKGROUND: Systematic characterization of how genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing.

RESULTS: We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic …

Quality Of Life Is Lower In Food Allergic Adolescents Compared To Young Children At A Community Educational Symposium, Diem-Tran I Nguyen, Kathleen Pitts, Kristen A Staggers, Carla M Davis

Faculty, Staff and Students Publications

INTRODUCTION: Food allergies (FA) can detrimentally impact physical, emotional, and psychological quality of life (QoL) among pediatric patients. Given the changes from childhood into adolescence, the impact of FA on QoL likely evolves with age. The purpose of this study was to determine whether QoL differed between adolescents and children with FA who participated in a Food Allergy Symposium (FAS).

METHODS: Patients with confirmed FA were recruited at an educational community symposium in September 2018 and September 2019. Patients and/or their parents were invited to complete the Food Allergy Quality of Life Questionnaires (FAQLQ). The Food Allergy Independent Measure (FAIM) …

Mechanisms Of Ferroptosis And Targeted Therapeutic Approaches In Lymphoma, Tiantian Yu, Zijun Y Xu-Monette, Li Yu, Yong Li, Ken H Young

Faculty, Staff and Students Publications

Lymphoma is the sixth most common type of cancer worldwide. Under the current treatment standards, patients with lymphoma often fail to respond to treatment or relapse early and require further therapy. Hence, novel therapeutic strategies need to be explored and our understanding of the molecular underpinnings of lymphomas should be expanded. Ferroptosis, a non-apoptotic regulated cell death, is characterized by increased reactive oxygen species and lipid peroxidation due to metabolic dysfunction. Excessive or lack of ferroptosis has been implicated in tumor development. Current preclinical evidences suggest that ferroptosis participates in tumorigenesis, progression, and drug resistance of lymphoma, identifying a potential …

Genetic Separation Of Brca1 Functions Reveal Mutation-Dependent Polθ Vulnerabilities, John J. Krais, David J. Glass, Ilse Chudoba, Yifan Wang, Wanjuan Feng, Dennis Simpson, Pooja Patel, Zemin Liu, Ryan Neumann-Domer, Robert G. Betsch, Andrea J. Bernhardy, Alice M. Bradbury, Jason Conger, Wei-Ting Yueh, Joseph Nacson, Richard T. Pomerantz, Gaorav P. Gupta, Joseph R. Testa, Neil Johnson

Department of Biochemistry and Molecular Biology Faculty Papers

Homologous recombination (HR)-deficiency induces a dependency on DNA polymerase theta (Polθ/Polq)-mediated end joining, and Polθ inhibitors (Polθi) are in development for cancer therapy. BRCA1 and BRCA2 deficient cells are thought to be synthetic lethal with Polθ, but whether distinct HR gene mutations give rise to equivalent Polθ-dependence, and the events that drive lethality, are unclear. In this study, we utilized mouse models with separate Brca1 functional defects to mechanistically define Brca1-Polθ synthetic lethality. Surprisingly, homozygous Brca1 mutant, Polq−/− cells were viable, but grew slowly and had chromosomal instability. Brca1 mutant cells proficient in DNA end resection were …

Exploring Alternative Treatment Choices For Multidrug-Resistant Clinical Strains Of Helicobacter Pylori In Mongolia, Ayush Khangai, Batsaikhan Saruuljavkhlan, Dashdorj Azzaya, Boldbaatar Gantuya, Khasag Oyuntsetseg, Junko Akada, Takashi Matsumoto, Yoshio Yamaoka

Faculty, Staff and Students Publications

Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia were considered. Minimal inhibitory concentrations for two fluoroquinolones (ciprofloxacin and moxifloxacin), rifabutin, and furazolidone were determined via two-fold agar dilution. Genomic mutations in antibiotic-resistant strains were identified by next-generation sequencing using the Illumina …

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

N6-Methyladenosine-Mediated Overexpression Of Long Noncoding Rna Adamts9-As2 Triggers Neuroblastoma Differentiation Via Regulating Lin28b/Let-7/Mycn Signaling, Yun Liu, Jun Zhang, Fang Cao, Xiaobao Dong, Jie Li, Yanna Cao, Zhanglin Li, Yan Guo, Jie Yan, Yuanyuan Liu, Qiang Zhao

Faculty, Staff and Student Publications

Neuroblastomas have shed light on the differentiation disorder that is associated with spontaneous regression or differentiation in the same tumor at the same time. Long noncoding RNAs (lncRNAs) actively participate in a broad spectrum of biological processes. However, the detailed molecular mechanisms underlying lncRNA regulation of differentiation in neuroblastomas remain largely unknown. Here, we sequenced clinical samples of ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. We compared transcription profiles of neuroblastoma cells, ganglion cells, and intermediate state cells; verified the profiles in a retinoic acid-induced cell differentiation model and clinical samples; and screened out the lncRNA ADAMTS9 antisense RNA 2 (ADAMTS9-AS2), which contributed …

Glial Cell Adhesion Molecule (Glialcam) Determines Proliferative Versus Invasive Cell States In Glioblastoma, Arpan De, John M Lattier, John E Morales, Jack R Kelly, Xiaofeng Zheng, Zhihua Chen, Sumod Sebastian, Zahra Nassiri Toosi, Jason T Huse, Frederick F Lang, Joseph H Mccarty

Faculty, Staff and Student Publications

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in subpopulations of GBM cells. High levels of GlialCAM promote …

Clinical, Genetic And Structural Delineation Of Rpl13-Related Spondyloepimetaphyseal Dysplasia Suggest Extra-Ribosomal Functions Of El1, Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham Srilakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene

Faculty, Staff and Students Publications

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, …

Dopamine, Norepinephrine And Serotonin Participate Differently In Methylphenidate Action In Concomitant Behavioral And Ventral Tegmental Area, Locus Coeruleus And Dorsal Raphe Neuronal Study In Young Rats, Cruz Reyes-Vasquez, Zachary Jones, Bin Tang, Nachum Dafny

Faculty, Staff and Student Publications

Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the synaptic cleft. Concomitant behavioral and neuronal recording from the ventral tegmental area (VTA), locus coeruleus (LC), and from the dorsal raphe (DR) nucleus, which are the sources of DA, NE, and 5-HT to the mesocorticolimbic circuit, were investigated following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD. Animals received daily saline or MPD administration on experimental days 1 to 6 (ED1–6), followed by a …

Hyperleptinemia Contributes To Antipsychotic Drug-Associated Obesity And Metabolic Disorders, Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M Kusminski, Ningyan Zhang, Zhiqiang An, Joel K Elmquist, Olivia Osborn, Chen Liu, Philipp E Scherer

Faculty, Staff and Students Publications

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly …

Distinct Transcriptomic Profiles In Children Prior To The Appearance Of Type 1 Diabetes-Linked Islet Autoantibodies And Following Enterovirus Infection, Jake Lin, Elaheh Moradi, Karoliina Salenius, Suvi Lehtipuro, Tomi Häkkinen, Jutta E Laiho, Sami Oikarinen, Sofia Randelin, Hemang M Parikh, Jeffrey P Krischer, Jorma Toppari, Åke Lernmark, Joseph F Petrosino, Nadim J Ajami, Jin-Xiong She, William A Hagopian, Marian J Rewers, Richard E Lloyd, Kirsi J Rautajoki, Heikki Hyöty, Matti Nykter, Teddy Study Group

Faculty, Staff and Students Publications

Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we …

Coregnet: Unraveling Gene Co-Regulation Networks From Public Rna-Seq Repositories Using A Beta-Binomial Statistical Model, Jiasheng Wang, Ying-Wooi Wan, Rami Al-Ouran, Meichen Huang, Zhandong Liu

Faculty, Staff and Students Publications

Millions of RNA sequencing samples have been deposited into public databases, providing a rich resource for biological research. These datasets encompass tens of thousands of experiments and offer comprehensive insights into human cellular regulation. However, a major challenge is how to integrate these experiments that acquired at different conditions. We propose a new statistical tool based on beta-binomial distributions that can construct robust gene co-regulation network (CoRegNet) across tens of thousands of experiments. Our analysis of over 12 000 experiments involving human tissues and cells shows that CoRegNet significantly outperforms existing gene co-expression-based methods. Although the majority of the genes …

Clinical, Genetic And Structural Delineation Of Rpl13-Related Spondyloepimetaphyseal Dysplasia Suggest Extra-Ribosomal Functions Of El13, Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham Srilakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene

Faculty, Staff and Students Publications

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, …

Pediatric Hiv+ Kaposi Sarcoma Exhibits Clinical, Virological, And Molecular Features Different From The Adult Disease, Carolina Caro-Vegas, Alice Peng, Angelica Juarez, Allison Silverstein, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Rizine Mzikamanda, Tamiwe Tomoka, Erin C Peckham-Gregory, Razia Moorad, Carrie L Kovarik, Liane R Campbell, Parth S Mehta, Peter N Kazembe, Carl E Allen, Michael E Scheurer, Nmazuo W Ozuah, Dirk P Dittmer, Nader Kim El-Mallawany

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND

Kaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.

METHODS

This was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were …