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Recombinant Netrin-4 Does Not Signal Through The Netrin-1 Or Netrin-3 Pathway In Tetrahymena Thermophila, Nicholas Bradley, Heather G. Kuruvilla 2019 Cedarville University

Recombinant Netrin-4 Does Not Signal Through The Netrin-1 Or Netrin-3 Pathway In Tetrahymena Thermophila, Nicholas Bradley, Heather G. Kuruvilla

The Research and Scholarship Symposium

Netrin 4 protein and its homologs are found throughout the animal kingdom. Netrin-4 is known to have a protective role against vascular damage. Previous studies have shown that human netrin-1 has a role in angiogenesis. This information about human netrin-1 and netrin-4 led us to research the pathway of netrin-4 in Tetrahymena thermophila. Our previous studies of the netrin proteins show that netrin-1 and netrin-3 are both repellents in Tetrahymena thermophila. The data in this study show that netrin-4 is also a repellent of Tetrahymena thermophila. These data suggest that netrin-4 could signal through the same pathway as netrin-1 and ...


Tetrahymena Thermophila Lack A Homologue Of The Caenorhabditis Elegans Lin-4 Mirna, Bryce H. Childers, Sorrel Paris, Emma Wessels, Heather G. Kuruvilla 2019 Cedarville University

Tetrahymena Thermophila Lack A Homologue Of The Caenorhabditis Elegans Lin-4 Mirna, Bryce H. Childers, Sorrel Paris, Emma Wessels, Heather G. Kuruvilla

The Research and Scholarship Symposium

The netrin family of proteins was first discovered because of their role in axonal guidance during development. Netrin homologues are important developmental signals in organisms ranging from vertebrates to the nematode, Caenorhabditis elegans, and netrin-like proteins have even been found in the ciliated protozoan, Tetrahymena thermophila. Since the lin-4 miRNA regulates netrin signaling in C. elegans, we hypothesized that a lin-4 homologue might exists in Tetrahymena thermophila. In order to test this hypothesis, we purified total miRNA from T. thermophila, used this miRNA to make cDNA, then used RT-PCR to quantitate the amount of lin-4 specific cDNA we obtained. Our ...


A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell 2019 Iowa State University

A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell

Genetics, Development and Cell Biology Publications

The unfolded protein response (UPR) is activated in plants in response to endoplasmic reticulum stress and plays an important role in mitigating stress damage. Multiple factors act in the UPR, including the membrane-associated transcription factor, BASIC LEUCINE ZIPPER 17 (bZIP17), and the membrane-associated RNA splicing factor, INOSITOL REQUIRING ENZYME1 (IRE1). We have analyzed an Arabidopsis (Arabidopsis thaliana) ire1a ire1b bzip17 triple mutant, with defects in stress signaling, and found that the mutant is also impaired in vegetative plant growth under conditions without externally applied stress. This raised the possibility that the UPR functions in plant development in the same manner ...


Arterial Distribution Of The Human Aorta: An Examination Of The Evolutionary, Developmental, And Physiological Bases Of Asymmetry., Brandon Oddo, Cooker Storm 2019 Pepperdine University

Arterial Distribution Of The Human Aorta: An Examination Of The Evolutionary, Developmental, And Physiological Bases Of Asymmetry., Brandon Oddo, Cooker Storm

Seaver College Research And Scholarly Achievement Symposium

The study of anatomy contends that “form follows function”; a disciplinary theme purporting that anatomical structures (i.e., cells, tissues, and organs) have a shape that serves its proper function. With this in mind, it is unclear why human arterial distribution off the aortic arch is asymmetrical, while the corresponding venous anatomy is symmetrical. We investigated the evolutionary, developmental, and physiological bases for the asymmetry of aortic arch branches in humans. First, we investigated the cardiovascular anatomy of ancestral species to determine if, and at what level, anatomical divergence (from aortic symmetry to asymmetry) occurs. Second, we examined the formation ...


Ultrafine Carbon Nanoparticles Activate Inflammasome Signaling And Cell Death In Murine Macrophages, Alexander Soloniuk, Hadley Lamascus, Jay Brewster, John Mann 2019 Pepperdine University

Ultrafine Carbon Nanoparticles Activate Inflammasome Signaling And Cell Death In Murine Macrophages, Alexander Soloniuk, Hadley Lamascus, Jay Brewster, John Mann

Seaver College Research And Scholarly Achievement Symposium

Carbon black (CB) is the primary nanoparticulate component of air pollution from fossil fuel combustion. This work examines the cellular impact of ultrafine carbon (carbon black, CB) nanoparticles, that range in size down to 30 nm, upon murine macrophages. The size analysis of the carbon black nanoparticles was performed using atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. RAW246.7 macrophage cells were exposed to CB doses ranging from 50 – 200 ug/ml in complete media. Analysis of cell survival over time revealed elevated rates of significant nuclear degradation and cell lifting after 48 hours of exposure, and ...


Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio 2019 University of Massachusetts Medical School

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine ...


Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo 2019 University of Massachusetts Medical School

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA ...


Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak 2019 Tufts University

Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak

Katherine A. Fitzgerald

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS ...


Identification Of Putative Regulatory Regions And Transcription Factors Associated With Intramuscular Fat Content Traits, Aline S. M. Cesar, Luciana C. A. Regitano, James M. Reecy, Mirele D. Poleti, Priscila S. N. Oliveira, Gabriella B. de Oliveira, Gabriel C. M. Moreira, Maurício A. Mudadu, Polyana C. Tizioto, James E. Koltes, Elyn Fritz-Waters, Luke Kramer, Dorian Garrick, Hamid Beiki, Ludwig Geistlinger, Gerson B. Mourão, Adhemar Zerlotini, Luiz L. Coutinho 2019 Iowa State University

Identification Of Putative Regulatory Regions And Transcription Factors Associated With Intramuscular Fat Content Traits, Aline S. M. Cesar, Luciana C. A. Regitano, James M. Reecy, Mirele D. Poleti, Priscila S. N. Oliveira, Gabriella B. De Oliveira, Gabriel C. M. Moreira, Maurício A. Mudadu, Polyana C. Tizioto, James E. Koltes, Elyn Fritz-Waters, Luke Kramer, Dorian Garrick, Hamid Beiki, Ludwig Geistlinger, Gerson B. Mourão, Adhemar Zerlotini, Luiz L. Coutinho

James M Reecy

Background: Integration of high throughput DNA genotyping and RNA-sequencing data allows for the identification of genomic regions that control gene expression, known as expression quantitative trait loci (eQTL), on a whole genome scale. Intramuscular fat (IMF) content and carcass composition play important roles in metabolic and physiological processes in mammals because they influence insulin sensitivity and consequently prevalence of metabolic diseases such as obesity and type 2 diabetes. However, limited information is available on the genetic variants and mechanisms associated with IMF deposition in mammals. Thus, our hypothesis was that eQTL analyses could identify putative regulatory regions and transcription factors ...


An Integrative Transcriptome Analysis Indicates Regulatory Mrna-Mirna Networks For Residual Feed Intake In Nelore Cattle, Priscila S.N. De Oliveira, Luiz L. Coutinho, Polyana C. Tizioto, Aline S. M. Cesar, Gabriella B. de Oliveira, Wellison J. da S. Diniz, Andressa O. De Lima, James M. Reecy, Gerson B. Mourão, Adhemar Zerlotini, Luciana C. A. Regitano 2019 Embrapa Pecuária Sudeste

An Integrative Transcriptome Analysis Indicates Regulatory Mrna-Mirna Networks For Residual Feed Intake In Nelore Cattle, Priscila S.N. De Oliveira, Luiz L. Coutinho, Polyana C. Tizioto, Aline S. M. Cesar, Gabriella B. De Oliveira, Wellison J. Da S. Diniz, Andressa O. De Lima, James M. Reecy, Gerson B. Mourão, Adhemar Zerlotini, Luciana C. A. Regitano

James M Reecy

Residual Feed Intake (RFI) is an economically relevant trait in beef cattle. Among the molecular regulatory mechanisms, microRNAs (miRNAs) are an important dimension in post-transcriptional regulation and have been associated with different biological pathways. Here, we performed differential miRNAs expression and weighted gene co-expression network analyses (WGCNA) to better understand the complex interactions between miRNAs and mRNAs expressed in bovine skeletal muscle and liver. MiRNA and mRNA expression data were obtained from Nelore steers that were genetically divergent for RFI (N = 10 [low RFI or feed efficient]; N = 10 [high RFI or feed inefficient]). Differentially expressed and hub miRNAs such ...


Molecular Basis For Strain Variation In The S. Cerevisiae Adhesion Flo11p, Li Li Ph.D., Subit Barua, Peter N. Lipke, Anne M. Dranginis 2019 Molloy College

Molecular Basis For Strain Variation In The S. Cerevisiae Adhesion Flo11p, Li Li Ph.D., Subit Barua, Peter N. Lipke, Anne M. Dranginis

Li Li

FLO11 encodes a yeast cell wall flocculin that mediates a variety of adhesive phenotypes in Saccharomyces cerevisiae. Flo11p is implicated in many developmental processes, including flocculation, formation of pseudohyphae, agar invasion, and formation of microbial mats and biofilms. However, Flo11p mediates different processes in different yeast strains. To investigate the mechanisms by which FLO11 determines these differences in colony morphology, flocculation, and invasion, we studied gene structure, function, and expression levels. Nonflocculent Saccharomyces cerevisiae Σ1278b cells exhibited significantly higher FLO11mRNA expression, especially in the stationary phase, than highly flocculent S. cerevisiae var. diastaticus. The two strains varied in cell ...


Expression And Characterization Of The Flocculin Flo11/Muc1, A Yeast Mannoprotein With Homotypic Properties Of Adhesion, Li Li Ph.D., Lois M. Douglas, Yang Yang, A M. Dranginis 2019 Molloy College

Expression And Characterization Of The Flocculin Flo11/Muc1, A Yeast Mannoprotein With Homotypic Properties Of Adhesion, Li Li Ph.D., Lois M. Douglas, Yang Yang, A M. Dranginis

Li Li

The Flo11/Muc1 flocculin has diverse phenotypic effects. Saccharomyces cerevisiae cells of strain background Σ1278b require Flo11p to form pseudohyphae, invade agar, adhere to plastic, and develop biofilms, but they do not flocculate. We show that S. cerevisiae var. diastaticusstrains, on the other hand, exhibit Flo11-dependent flocculation and biofilm formation but do not invade agar or form pseudohyphae. In order to study the nature of the Flo11p proteins produced by these two types of strains, we examined secreted Flo11p, encoded by a plasmid-borne gene, in which the glycosylphosphatidylinositol anchor sequences had been replaced by a histidine tag. A protein ...


Large-Scale Gene Co-Expression Network As A Source Of Functional Annotation For Cattle Genes, Hamid Beiki, Ardeshir Nejati-Javaremi, Abbas Pakdel, Ali Masoudi-Nejad, Zhi-Liang Hu, James M. Reecy 2019 Iowa State University

Large-Scale Gene Co-Expression Network As A Source Of Functional Annotation For Cattle Genes, Hamid Beiki, Ardeshir Nejati-Javaremi, Abbas Pakdel, Ali Masoudi-Nejad, Zhi-Liang Hu, James M. Reecy

James M Reecy

Background: Genome sequencing and subsequent gene annotation of genomes has led to the elucidation of many genes, but in vertebrates the actual number of protein coding genes are very consistent across species (~20,000). Seven years after sequencing the cattle genome, there are still genes that have limited annotation and the function of many genes are still not understood, or partly understood at best. Based on the assumption that genes with similar patterns of expression across a vast array of tissues and experimental conditions are likely to encode proteins with related functions or participate within a given pathway, we constructed ...


Differences In The Skeletal Muscle Transcriptome Profile Associated With Extreme Values Of Fatty Acids Content, Aline S. M. Cesar, Luciana C. A. Regitano, Mirele D. Poleti, Sónia C. S. Andrade, Polyana C. Tizioto, Priscila S. N. Oliveira, Andrezza M. Felício, Michele L. do Nascimento, Amália S. Chaves, Dante P. D. Lanna, Rymer R. Tullio, Renata T. Nassu, James E. Koltes, Eric Frtiz-Waters, Gerson B. Mourão, Adhemar Zerlotini-Neto, James M. Reecy, Luiz L. Coutinho 2019 Iowa State University

Differences In The Skeletal Muscle Transcriptome Profile Associated With Extreme Values Of Fatty Acids Content, Aline S. M. Cesar, Luciana C. A. Regitano, Mirele D. Poleti, Sónia C. S. Andrade, Polyana C. Tizioto, Priscila S. N. Oliveira, Andrezza M. Felício, Michele L. Do Nascimento, Amália S. Chaves, Dante P. D. Lanna, Rymer R. Tullio, Renata T. Nassu, James E. Koltes, Eric Frtiz-Waters, Gerson B. Mourão, Adhemar Zerlotini-Neto, James M. Reecy, Luiz L. Coutinho

James M Reecy

Background: Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene ...


Bioinformatic Analyses In Early Host Response To Porcine Reproductive And Respiratory Syndrome Virus (Prrsv) Reveals Pathway Differences Between Pigs With Alternate Genotypes For A Major Host Response Qtl, Martine Schroyen, Christopher Eisley, James E. Koltes, Eric Fritz-Waters, Igseo Choi, Graham S. Plastow, Leluo Guan, Paul Stothard, Hua Bao, Arun Kommadath, James M. Reecy, Joan K. Lunney, Robert R. R. Rowland, Jack C. M. Dekkers, Christopher K. Tuggle 2019 Iowa State University

Bioinformatic Analyses In Early Host Response To Porcine Reproductive And Respiratory Syndrome Virus (Prrsv) Reveals Pathway Differences Between Pigs With Alternate Genotypes For A Major Host Response Qtl, Martine Schroyen, Christopher Eisley, James E. Koltes, Eric Fritz-Waters, Igseo Choi, Graham S. Plastow, Leluo Guan, Paul Stothard, Hua Bao, Arun Kommadath, James M. Reecy, Joan K. Lunney, Robert R. R. Rowland, Jack C. M. Dekkers, Christopher K. Tuggle

James M Reecy

Background: A region on Sus scrofa chromosome 4 (SSC4) surrounding single nucleotide polymorphism (SNP) marker WUR10000125 (WUR) has been reported to be strongly associated with both weight gain and serum viremia in pigs after infection with PRRS virus (PRRSV). A proposed causal mutation in the guanylate binding protein 5 gene (GBP5) is predicted to truncate the encoded protein. To investigate transcriptional differences between WUR genotypes in early host response to PRRSV infection, an RNA-seq experiment was performed on globin depleted whole blood RNA collected on 0, 4, 7, 10 and 14 days post-infection (dpi) from eight littermate pairs with one ...


Head And Neck Cancers, James Liebmann, Ali Akalin, Liana Puscas, Andrew Chen, Richard S. Pieters 2019 University of Massachusetts Medical School

Head And Neck Cancers, James Liebmann, Ali Akalin, Liana Puscas, Andrew Chen, Richard S. Pieters

Cancer Concepts: A Guidebook for the Non-Oncologist

This chapter in Cancer Concepts: A Guidebook for the Non-Oncologist presents an overview of head and neck cancers, including epidemiology, etiology, screening, pathology, staging, and treatment. The chapter focuses on cancers of the upper aerodigestive tract which are most often squamous cell carcinomas arising from the squamous epithelium that lines the tract.


Endosome To Golgi Retrieval Of The Vacuolar Protein Sorting Receptor, Vps10p, Requires The Function Of The Vps29, Vps30, And Vps35 Gene Products, Matthew N. J. Seaman, Eric G. Marcusson, Joan Lin-Cereghino, Scott D. Emr 2019 University of California, San Diego

Endosome To Golgi Retrieval Of The Vacuolar Protein Sorting Receptor, Vps10p, Requires The Function Of The Vps29, Vps30, And Vps35 Gene Products, Matthew N. J. Seaman, Eric G. Marcusson, Joan Lin-Cereghino, Scott D. Emr

Joan Lin-Cereghino

Mutations in the S. cerevisiae VPS29 and VPS30 genes lead to a selective protein sorting defect in which the vacuolar protein carboxypeptidase Y (CPY) is missorted and secreted from the cell, while other soluble vacuolar hydrolases like proteinase A (PrA) are delivered to the vacuole. This phenotype is similar to that seen in cells with mutations in the previously characterized VPS10 and VPS35 genes. Vps10p is a late Golgi transmembrane protein that acts as the sorting receptor for soluble vacuolar hydrolases like CPY and PrA, while Vps35p is a peripheral membrane protein which cofractionates with membranes enriched in Vps10p. The ...


A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang 2019 Massachusetts General Hospital & University of Nebraska Medical Center & Huazhong Agricultural University

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Virology Papers

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 ...


Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas 2019 Harvard Medical School

Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas

Open Access Articles

The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq ...


Investigating The Role Of Free Radicals In Huntington's Disease Using Drosophila Melanogaster, Jennifer Libov 2019 University of Nebraska - Lincoln

Investigating The Role Of Free Radicals In Huntington's Disease Using Drosophila Melanogaster, Jennifer Libov

Honors Theses, University of Nebraska-Lincoln

During normal cell metabolism, reactive oxygen species (ROS) are produced as a byproduct of oxidative phosphorylation. ROS are utilized in the cell as a signaling molecule and can be maintained at healthy levels by cellular antioxidants. However, when the cell experiences oxidative stress due to environmental or genetic conditions, levels of ROS can exceed healthy levels and inhibit necessary life functions by damaging biomolecules and cellular structures. This loss of function can lead to physiological decline and neurodegeneration, such as in diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and, potentially, Huntington’s disease. The following experiments use the model ...


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