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- BRC (2)
- Cancer (2)
- Cellular control mechanisms (2)
- DNA repair (2)
- Escherichia coli (2)
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- Gene expression (2)
- Killifishes (2)
- Killifishes -- Diapause (2)
- Ultraviolet radiation (2)
- Amblyomma -- Phylogeny (1)
- Amblyomma americanum (1)
- Animals as carriers of disease (1)
- Anoxemia -- Molecular aspects (1)
- Antigen-antibody reactions (1)
- B cells (1)
- Binding proteins (1)
- Bones -- Growth -- Effect of VItamin D on (1)
- Carrier proteins (1)
- Cell migration (1)
- Cellular processes (1)
- Coxiella burnetii -- Genetic transcription (1)
- Cyclin-dependent kinases (1)
- DICER1 germline mutations (1)
- DICER1 syndrome (1)
- DNA ligases (1)
- DNA repair -- Molecular aspects (1)
- Diapause (1)
- Endonucleases (1)
- Endosymbiosis (1)
- Endotoxins (1)
Articles 1 - 21 of 21
Full-Text Articles in Life Sciences
Trem2 Is Thyroid Hormone Regulated Making The Trem2 Pathway Druggable With Ligands For Thyroid Hormone Receptor., Skylar J. Ferrara, Priya Chaudhary, Margaret J. Debell, Gail Marracci, Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier, Ben Emery, Dennis Bourdette, Thomas S. Scanlan
Trem2 Is Thyroid Hormone Regulated Making The Trem2 Pathway Druggable With Ligands For Thyroid Hormone Receptor., Skylar J. Ferrara, Priya Chaudhary, Margaret J. Debell, Gail Marracci, Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier, Ben Emery, Dennis Bourdette, Thomas S. Scanlan
Biology Faculty Publications and Presentations
Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease-associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. Here, we report that TREM2 is a thyroid hormone-regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone and synthetic thyroid hormone agonists (thyromimetics). Our findings report the endocrine regulation of TREM2 by thyroid hormone, and provide a …
Modulation Of Bacterial Fitness And Virulence Through Antisense Rnas, Jess A. Millar, Rahul Raghavan
Modulation Of Bacterial Fitness And Virulence Through Antisense Rnas, Jess A. Millar, Rahul Raghavan
Biology Faculty Publications and Presentations
Regulatory RNAs contribute to gene expression control in bacteria. Antisense RNAs (asRNA) are a class of regulatory RNAs that are transcribed from opposite strands of their target genes. Typically, these untranslated transcripts bind to cognate mRNAs and rapidly regulate gene expression at the post-transcriptional level. In this article, we review asRNAs that modulate bacterial fitness and increase virulence. We chose examples that underscore the variety observed in nature including, plasmid- and chromosome-encoded asRNAs, a riboswitch-regulated as RNA, and as RNAs that require other RNAs or RNA binding proteins for stability and activity. We explore how as RNAs improve bacterial fitness …
A Rapid Caspase-11 Response Induced By Ifng Priming Is Independent Of Guanylate Binding Proteins, Sky W. Brubaker, Susan M. Brewer, Liliana M. Massis, Brooke A. Napier, Denise M. Monack
A Rapid Caspase-11 Response Induced By Ifng Priming Is Independent Of Guanylate Binding Proteins, Sky W. Brubaker, Susan M. Brewer, Liliana M. Massis, Brooke A. Napier, Denise M. Monack
Biology Faculty Publications and Presentations
In mammalian cells, inflammatory caspases detect Gram-negative bacterial invasion by binding lipopolysaccharides (LPS). Murine caspase-11 binds cytosolic LPS, stimulates pyroptotic cell death, and drives sepsis pathogenesis. Extracellular priming factors enhance caspase-11-dependent pyroptosis. Herein we compare priming agents and demonstrate that IFNγ priming elicits the most rapid and amplified macrophage response to cytosolic LPS. Previous studies indicate that IFN-induced expression of caspase-11 and guanylate binding proteins (GBPs) are causal events explaining the effects of priming on cytosolic LPS sensing. We demonstrate that these events cannot fully account for the increased response triggered by IFNγ treatment. Indeed, IFNγ priming …
Cul3 Regulates Cyclin E1 Protein Abundance Via A Degron Located Within The N-Terminal Region Of Cyclin E, Brittney Marie Davidge, Katia De Oliveira Rebola, Larry N. Agbor, Curt D. Sigmund, Jeffrey D. Singer
Cul3 Regulates Cyclin E1 Protein Abundance Via A Degron Located Within The N-Terminal Region Of Cyclin E, Brittney Marie Davidge, Katia De Oliveira Rebola, Larry N. Agbor, Curt D. Sigmund, Jeffrey D. Singer
Biology Faculty Publications and Presentations
mammalian cells. Increased levels of cyclin E are found in some cancers. Additionally, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with increased cyclin E–Cdk2 activity and poor clinical prognosis. Cyclin E levels are tightly regulated and controlled in part through ubiquitin-mediated degradation initiated by one of two E3 ligases, Cul1 and Cul3. Cul1 ubiquitylates phosphorylated cyclin E, but the mechanism through which Cul3 ubiquitylates cyclin E is poorly understood. In experiments to ascertain how Cul3 mediates cyclin E destruction, we identified a degron on cyclin E that Cul3 targets for ubiquitylation. Recognition of …
Disruption Of Cul3-Mediated Ubiquitination Causes Proximal Tubule Injury And Kidney Fibrosis, Turgay Saritas, Catherina A. Cuevas, Mohammed Z. Ferdaus, Christophe Kuppe, Rafael Kramann, Marcus J. Moeller, Jurgen Floege, Jeffrey Singer, James A. Mccormick
Disruption Of Cul3-Mediated Ubiquitination Causes Proximal Tubule Injury And Kidney Fibrosis, Turgay Saritas, Catherina A. Cuevas, Mohammed Z. Ferdaus, Christophe Kuppe, Rafael Kramann, Marcus J. Moeller, Jurgen Floege, Jeffrey Singer, James A. Mccormick
Biology Faculty Publications and Presentations
Cullin 3 (CUL3) is part of the ubiquitin proteasomal system and controls several cellular processes critical for normal organ function including the cell cycle, and Keap1/Nrf2 signaling. Kidney tubule-specific Cul3disruption causes tubulointerstitial fibrosis, but little is known about the mechanisms. Therefore, we tested the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway play a role in initiating the kidney injury upon Cul3 disruption. Cul3 deletion increased expression of cyclin E and p21, associated with uncontrolled proliferation, DNA damage, and apoptosis, all of which preceded proximal tubule injury. The cdk2-cyclin E inhibitor roscovitine did not prevent the effects …
Genome Sequences Of Three Cruciviruses Found In The Willamette Valley (Oregon), Ignacio De La Higuera, Ellis L. Torrance, Alyssa A. Pratt, George Kasun, Amberlee Maluenda, Kenneth M. Stedman
Genome Sequences Of Three Cruciviruses Found In The Willamette Valley (Oregon), Ignacio De La Higuera, Ellis L. Torrance, Alyssa A. Pratt, George Kasun, Amberlee Maluenda, Kenneth M. Stedman
Biology Faculty Publications and Presentations
Cruciviruses are single-stranded DNA (ssDNA) viruses whose genomes suggest the possibility of gene transfer between DNA and RNA viruses. Many crucivirus genome sequences have been found in metagenomic data sets, although no crucivirus has been isolated. Here, we present the complete genome sequences of three cruciviruses recovered from environmental samples from Oregon.
Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish, Amie L. Romney, Jason E. Podrabsky
Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish, Amie L. Romney, Jason E. Podrabsky
Biology Faculty Publications and Presentations
Embryonic development of Austrofundulus limnaeus can occur along two phenotypic trajectories that are physiologically and biochemically distinct. Phenotype appears to be influenced by maternal provisioning based on the observation that young females produce predominately non-diapausing embryos and older females produce mostly diapausing embryos. Embryonic incubation temperature can override this pattern and alter trajectory. We hypothesized that temperature-induced phenotypic plasticity may be regulated by post-transcriptional modification via noncoding RNAs. As a first step to exploring this possibility, RNA-seq was used to generate transcriptomic profiles of small noncoding RNAs in embryos developing along the two alternative trajectories. We find distinct profiles of …
Sexually Dimorphic Patterns Of Cell Proliferation In The Brain Are Linked To Seasonal Life-History Transitions In Red-Sided Garter Snakes, Deborah Lutterschmidt, Ashley R. Lucas, Ritta A. Karam, Vicky T. Nguyen, Meghann R. Rasmussen
Sexually Dimorphic Patterns Of Cell Proliferation In The Brain Are Linked To Seasonal Life-History Transitions In Red-Sided Garter Snakes, Deborah Lutterschmidt, Ashley R. Lucas, Ritta A. Karam, Vicky T. Nguyen, Meghann R. Rasmussen
Biology Faculty Publications and Presentations
Seasonal rhythms in physiology and behavior are widespread across diverse taxonomic groups and may be mediated by seasonal changes in neurogenesis, including cell proliferation, migration, and differentiation. We examined if cell proliferation in the brain is associated with the seasonal life-history transition from spring breeding to migration and summer foraging in a free-ranging population of red-sided garter snakes (Thamnophis sirtalis) in Manitoba, Canada. We used the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) to label newly proliferated cells within the brain of adult snakes collected from the den during the mating season or from a road located along their migratory route. …
Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford
Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford
Biology Faculty Publications and Presentations
DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions …
Baseline Mrna Expression Differs Widely Between Common Laboratory Strains Of Zebrafish, Lindsay Holden, Kim H. Brown
Baseline Mrna Expression Differs Widely Between Common Laboratory Strains Of Zebrafish, Lindsay Holden, Kim H. Brown
Biology Faculty Publications and Presentations
Common strains of wildtype zebrafish (Danio rerio) have unique genomic features including SNPs and CNV, but strain information often goes unreported in the literature. As a result, the confounding effects of interstrain variation makes repetition of studies in zebrafish challenging. Here we analyze hepatic mRNA expression patterns between three common zebrafish strains (AB, Tuebingen (TU), and WIK) using Agilent 4 × 44 K gene expression microarrays to establish baseline mRNA expression across strains and between sexes. We observed wide variation in sex-specific gene expression within AB and WIK strains (141 genes in AB and 67 genes in WIK), …
Plasma Cell Survival In The Absence Of B Cell Memory, Erika Hammarlund, Archana Thomas, Ian J. Amanna, Lindsay Holden, Ov D. Slayden, Byung S. Park, Lina Gao, Mark K. Slifka
Plasma Cell Survival In The Absence Of B Cell Memory, Erika Hammarlund, Archana Thomas, Ian J. Amanna, Lindsay Holden, Ov D. Slayden, Byung S. Park, Lina Gao, Mark K. Slifka
Biology Faculty Publications and Presentations
Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear. Clinical studies indicate that antigen-specific antibody responses can be maintained for many years, leading to theories that reactivation/differentiation of memory B cells into plasma cells is required to sustain long-term antibody production. Here, we present a decade-long study in which we demonstrate site-specific survival of bone marrow-derived plasma cells and durable antibody responses to multiple virus and vaccine antigens in rhesus macaques for years after sustained memory B cell depletion. Moreover, BrdU+ cells with plasma cell morphology can be …
Transcriptomic Analysis Of Maternally Provisioned Cues For Phenotypic Plasticity In The Annual Killifish, Austrofundulus Limnaeus, Amie L. Romney, Jason E. Podrabsky
Transcriptomic Analysis Of Maternally Provisioned Cues For Phenotypic Plasticity In The Annual Killifish, Austrofundulus Limnaeus, Amie L. Romney, Jason E. Podrabsky
Biology Faculty Publications and Presentations
Background: Genotype and environment can interact during development to produce novel adaptive traits that support life in extreme conditions. The development of the annual killifsh Austrofundulus limnaeus is unique among vertebrates because the embryos have distinct cell movements that separate epiboly from axis formation during early development, can enter into a state of metabolic dormancy known as diapause and can survive extreme environmental conditions. The ability to enter into diapause can be maternally programmed, with young females producing embryos that do not enter into diapause. Alternately, embryos can be programmed to “escape” from diapause and develop directly by both maternal …
Gene Expression Patterns That Support Novel Developmental Stress Buffering In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Josiah T. Wagner, Jason E. Podrabsky
Gene Expression Patterns That Support Novel Developmental Stress Buffering In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Josiah T. Wagner, Jason E. Podrabsky
Biology Faculty Publications and Presentations
Background: The cellular signaling mechanisms and morphogenic movements involved in axis formation and gastrulation are well conserved between vertebrates. In nearly all described fish, gastrulation and the initial patterning of the embryonic axis occur concurrently with epiboly. However, annual killifish may be an exception to this norm. Annual killifish inhabit ephemeral ponds in South America and Africa and permanent populations persist by the production of stress-tolerant eggs. Early development of annual killifish is unique among vertebrates because their embryonic blastomeres disperse randomly across the yolk during epiboly and reaggregate several days later to form the embryo proper. In addition, annual …
A Coxiella-Like Endosymbiont Is A Potential Vitamin Source For The Lone Star Tick, Todd A. Smith, Timothy Driscoll, Joseph J. Gillespie, Rahul Raghavan
A Coxiella-Like Endosymbiont Is A Potential Vitamin Source For The Lone Star Tick, Todd A. Smith, Timothy Driscoll, Joseph J. Gillespie, Rahul Raghavan
Biology Faculty Publications and Presentations
Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness. Blood-feeding insects (Class Insecta) depend on bacterial endosymbionts to provide vitamins and cofactors that are scarce in blood. It is unclear how this deficiency is compensated in ticks (Class Arachnida) that feed exclusively on mammalian blood. A bacterium related to Coxiella burnetii, the agent of human Q fever, has been observed previously within cells of A. americanum. Eliminating this bacterium (CLEAA, Coxiella-like endosymbiont of A. americanum) with antibiotics …
Identification Of Novel Small Rnas And Characterization Of The 6s Rna Of Coxiella Burnetii, Indu Warrier, Linda D. Hicks, James M. Battisti, Rahul Raghavan, Michael F. Minnick
Identification Of Novel Small Rnas And Characterization Of The 6s Rna Of Coxiella Burnetii, Indu Warrier, Linda D. Hicks, James M. Battisti, Rahul Raghavan, Michael F. Minnick
Biology Faculty Publications and Presentations
Coxiella burnetii, an obligate intracellular bacterial pathogen that causes Q fever, undergoes a biphasic developmental cycle that alternates between a metabolically-active large cell variant (LCV) and a dormant small cell variant (SCV). As such, the bacterium undoubtedly employs complex modes of regulating its lifecycle, metabolism and pathogenesis. Small RNAs (sRNAs) have been shown to play important regulatory roles in controlling metabolism and virulence in several pathogenic bacteria. We hypothesize that sRNAs are involved in regulating growth and development of C. burnetii and its infection of host cells. To address the hypothesis and identify potential sRNAs, we subjected total RNA isolated …
Matrix Gla Protein Reinforces Angiogenic Resolution, Bikram Sharma, Allan R. Albig
Matrix Gla Protein Reinforces Angiogenic Resolution, Bikram Sharma, Allan R. Albig
Biology Faculty Publications and Presentations
Matrix Gla Protein (MGP) is an ECM molecule commonly associated with dysfunctions of large blood vessels such as arteriosclerosis and atherosclerosis. However, the exact role of MGP in the microvasculature is not clear. Utilizing a mouse MGP knockout model we found that MGP suppresses angiogenic sprouting from mouse aorta restricts microvascular density in cardiac and skeletal muscle, and is an endogenous inhibitor of tumor angiogenesis. Similarly, morpholino based knockdown of MGP in zebrafish embryos caused a progressive loss of luminal structures in intersegmental vessels, a phenotype reminiscent of Dll4/Notch inhibition. Accordingly, MGP suppressed Notch-dependent Hes-1 promoter activity and expression of …
Extrahepatic 25-Hydroxylation Of Vitamin D3 In An Engineered Osteoblast Precursor Cell Line Exploring The Influence On Cellular Proliferation And Matrix Maturation During Bone Development, Shelley S. Mason, Sean S. Kohles, Shelley R. Winn, Randy D. Zelick
Extrahepatic 25-Hydroxylation Of Vitamin D3 In An Engineered Osteoblast Precursor Cell Line Exploring The Influence On Cellular Proliferation And Matrix Maturation During Bone Development, Shelley S. Mason, Sean S. Kohles, Shelley R. Winn, Randy D. Zelick
Biology Faculty Publications and Presentations
Osteoblastic precursors experience distinct stages during differentiation and bone development, which include proliferation, extracellular matrix (ECM) maturation, and ECM mineralization. It is well known that vitamin D plays a large role in the regulation of bone mineralization and homeostasis via the endocrine system. The activation of vitamin D requires two sequential hydroxylation steps, first in the kidney and then in the liver, in order to carry out its role in calcium homeostasis. Recent research has demonstrated that human-derived mesenchymal stem cells (MSCs) and osteoblasts can metabolize the immediate vitamin D precursor 25- dihydroxyvitamin D₃(25OH₂D₃) to the active steroid 1α,25-dihydroxyvitamin D₃ …
Inefficient Replication Reduces Reca-Mediated Repair Of Uvdamaged Plasmids Introduced Into Competent Escherichia Coli, Harout Arthur Jeiranian, Charmain T. Courcelle, Justin Courcelle
Inefficient Replication Reduces Reca-Mediated Repair Of Uvdamaged Plasmids Introduced Into Competent Escherichia Coli, Harout Arthur Jeiranian, Charmain T. Courcelle, Justin Courcelle
Biology Faculty Publications and Presentations
Transformation of Escherichia coli with purified plasmids containing DNA damage is frequently used as a tool to characterize repair pathways that operate on chromosomes. In this study, we used an assay that allowed us to quantify plasmid survival and to compare how efficiently various repair pathways operate on plasmid DNA introduced into cells relative to their efficiency on chromosomal DNA. We observed distinct differences between the mechanisms operating on the transforming plasmid DNA and the chromosome. An average of one UV-induced lesion was sufficient to inactivate ColE1-based plasmids introduced into nucleotide excision repair mutants, suggesting an essential role for repair …
Uvrd Participation In Nucleotide Excision Repair Is Required For The Recovery Of Dna Synthesis Following Uv-Induced Damage In Escherichia Coli, Kelley Nicole Newton, Charmain T. Courcelle, Justin Courcelle
Uvrd Participation In Nucleotide Excision Repair Is Required For The Recovery Of Dna Synthesis Following Uv-Induced Damage In Escherichia Coli, Kelley Nicole Newton, Charmain T. Courcelle, Justin Courcelle
Biology Faculty Publications and Presentations
UvrD is a DNA helicase that participates in nucleotide excision repair and several replication-associated processes, including methyl-directed mismatch repair and recombination. UvrD is capable of displacing oligonucleotides from synthetic forked DNA structures in vitro and is essential for viability in the absence of Rep, a helicase associated with processing replication forks. These observations have led others to propose that UvrD may promote fork regression and facilitate resetting of the replication fork following arrest. However, the molecular activity of UvrD at replication forks in vivo has not been directly examined. In this study, we characterized the role UvrD has in processing …
Escherichia Coli Fpg Glycosylase Is Nonrendundant And Required For The Rapid Global Repair Of Oxidized Purine And Pyrimidine Damage In Vivo, Brandy J. Schalow, Charmain T. Courcelle, Justin Courcelle
Escherichia Coli Fpg Glycosylase Is Nonrendundant And Required For The Rapid Global Repair Of Oxidized Purine And Pyrimidine Damage In Vivo, Brandy J. Schalow, Charmain T. Courcelle, Justin Courcelle
Biology Faculty Publications and Presentations
Endonuclease (Endo) III and formamidopyrimidine-N-glycosylase (Fpg) are two of the predominant DNA glycosylases in Escherichia coli that remove oxidative base damage. In cell extracts and purified form, Endo III is generally more active toward oxidized pyrimidines, while Fpg is more active towards oxidized purines. However, the substrate specificities of these enzymes partially overlap in vitro. Less is known about the relative contribution of these enzymes in restoring the genomic template following oxidative damage. In this study, we examined how efficiently Endo III and Fpg repair their oxidative substrates in vivo following treatment with hydrogen peroxide. We found …
Mitochondrial Physiology Of Diapausing And Developing Embryos Of The Annual Killifish Austrofundulus Limnaeus: Implications For Extreme Anoxia Tolerance, Jeffrey M. Duerr, Jason E. Podrabsky
Mitochondrial Physiology Of Diapausing And Developing Embryos Of The Annual Killifish Austrofundulus Limnaeus: Implications For Extreme Anoxia Tolerance, Jeffrey M. Duerr, Jason E. Podrabsky
Biology Faculty Publications and Presentations
Diapausing embryos of the annual killifish Austrofundulus limnaeus have the highest reported anoxia tolerance of any vertebrate and previous studies indicate modified mitochondrial physiology likely supports anoxic metabolism. Functional mitochondria isolated from diapausing and developing embryos of the annual killifish exhibited VO2, respiratory control ratios (RCR), and P:O ratios consistent with those obtained from other ectothermic vertebrate species. Reduced oxygen consumption associated with dormancy in whole animal respiration rates are correlated with maximal respiration rates of mitochondria isolated from diapausing versus developing embryos. P:O ratios for developing embryos were similar to those obtained from adult liver, but were diminished in …