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Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews Mar 2019

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Tyler Johnson

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …


Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela Feb 2019

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Tyler Johnson

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …


Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews Feb 2019

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews

Tyler Johnson

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …


The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou Feb 2019

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou

Tyler Johnson

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …


Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn Feb 2019

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn

Tyler Johnson

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …


The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg Jun 2017

The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg

Jenny Ekberg

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory …


An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls Sep 2016

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …


Wild Justice Redux: What We Know About Social Justice In Animals And Why It Matters, Jessica Pierce, Marc Bekoff Sep 2016

Wild Justice Redux: What We Know About Social Justice In Animals And Why It Matters, Jessica Pierce, Marc Bekoff

Marc Bekoff, PhD

Social justice in animals is beginning to attract interest in a broad range of academic disciplines. Justice is an important area of study because it may help explain social dynamics among individuals living in tightly- knit groups, as well as social interactions among individuals who only occasionally meet. In this paper, we provide an overview of what is currently known about social justice in animals and offer an agenda for further research. We provide working definitions of key terms, outline some central research questions, and explore some of the challenges of studying social justice in animals, as well as the …


The Ethics Of Wildlife Control In Humanized Landscapes, John Hadidian, Camilla H. Fox, William S. Lynn Aug 2016

The Ethics Of Wildlife Control In Humanized Landscapes, John Hadidian, Camilla H. Fox, William S. Lynn

William S. Lynn, PhD

The 21st century is witness to an unprecedented and rapid growth of human settlements, from urban centers to wilderness vacation resorts. Concurrent with this has been the growing tolerance and acceptance of many wild animals and humans for one another. This has created an expanding ‘zone’ of human-animal contacts, some number of which invariably result in conflicts. While the vast majority of our interactions with wild animals are undoubtedly benign, it is the conflict between wildlife and people that draws particularly close attention from the public. Animals viewed as vertebrate “pests” range from the small to the large, the timid …


Bone Morphogenetic Protein Receptor Type Ia Localization Causes Increased Bmp2 Signaling In Mice Exhibiting Increased Peak Bone Mass Phenotype., Beth Bragdon, Jeremy Bonor, Kathryn L Shultz, Wesley G Beamer, Clifford J Rosen, Anja Nohe Jan 2016

Bone Morphogenetic Protein Receptor Type Ia Localization Causes Increased Bmp2 Signaling In Mice Exhibiting Increased Peak Bone Mass Phenotype., Beth Bragdon, Jeremy Bonor, Kathryn L Shultz, Wesley G Beamer, Clifford J Rosen, Anja Nohe

Clifford J Shultz

Bone morphogenetic protein 2 (BMP2) is a growth factor that initiates osteoblast differentiation. Recent studies show that BMP2 signaling regulates bone mineral density (BMD). BMP2 interacts with BMP receptor type Ia (BMPRIa) and type II receptor leading to the activation of the Smad signaling pathway. BMPRIa must shuttle between distinct plasma membrane domains, enriched of Caveolin-1 alpha and Caveolin-1 beta isoforms, and receptor activation occurs in these domains. Yet it remains unknown whether the molecular mechanism that regulates BMP2 signaling is driving mineralization and BMD. Therefore, the B6.C3H-1-12 congenic mouse model with increased BMD and osteoblast mineralization was utilized in …


Influence Of Env And Long Terminal Repeat Sequences On The Tissue Tropism Of Avian Leukosis Viruses, David Brown, Harriet Robinson Dec 2015

Influence Of Env And Long Terminal Repeat Sequences On The Tissue Tropism Of Avian Leukosis Viruses, David Brown, Harriet Robinson

David C. Brown

Adsorption and penetration of retroviruses into eucaryotic cells is mediated by retroviral envelope glycoproteins interacting with host receptors. Recombinant avian leukosis viruses (ALVs) differing only in envelope determinants that interact with host receptors for subgroup A or E ALVs have been found to have unexpectedly distinctive patterns of tissue-specific replication. Recombinants of both subgroups were highly expressed in bursal lymphocytes as well as in cultured chicken embryo fibroblasts. In contrast, the subgroup A but not subgroup E host range allowed high levels of expression in skeletal muscle, while subgroup E but not subgroup A envelope glycoproteins permitted efficient replication in …


Infection Of Peripancreatic Lymph Nodes But Not Islets Precedes Kilham Rat Virus-Induced Diabetes In Bb/Wor Rats, David Brown, Raymond Welsh, Arthur Like Dec 2015

Infection Of Peripancreatic Lymph Nodes But Not Islets Precedes Kilham Rat Virus-Induced Diabetes In Bb/Wor Rats, David Brown, Raymond Welsh, Arthur Like

David C. Brown

A parvovirus serologically identified as Kilham rat virus (KRV) reproducibly induces acute type I diabetes in diabetes-resistant BB/Wor rats. The tissue tropism of KRV was investigated by in situ hybridization with a digoxigenin-labelled plasmid DNA probe containing approximately 1.6 kb of the genome of the UMass isolate of KRV. Partial sequencing of the KRV probe revealed high levels of homology to the sequence of minute virus of mice (89%) and to the sequence of H1 (99%), a parvovirus capable of infecting rats and humans. Of the 444 bases sequenced, 440 were shared by H1. KRV mRNA and DNA were readily …


Biaxial Failure Properties Of Planar Living Tissue Equivalents, Kristen Billiar, Angela Throm, Margo Frey Dec 2015

Biaxial Failure Properties Of Planar Living Tissue Equivalents, Kristen Billiar, Angela Throm, Margo Frey

Kristen L. Billiar

Quantification of the mechanical properties of living tissue equivalents (LTEs) is essential for assessing their ultimate functionality as tissue substitutes, yet their delicate nature makes failure testing problematic. For this study, we evaluated the validity of using an inflation device for quantifying the biaxial tensile failure properties of extremely delicate fibroblast-populated collagen gels (CGs) and fibrin gels (FGs). Small samples were circularly clamped and then inflated until rupture. Each sample assumed an approximately spherical shape and burst at its center indicating effective clamping. After two weeks in culture, all LTEs tested were fragile, but the FGs were significantly stronger and …


Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert Dec 2015

Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert

Robert J. Gegear

Humans are not believed to have a magnetic sense, even though many animals use the Earth's magnetic field for orientation and navigation. One model of magnetosensing in animals proposes that geomagnetic fields are perceived by light-sensitive chemical reactions involving the flavoprotein cryptochrome (CRY). Here we show using a transgenic approach that human CRY2, which is heavily expressed in the retina, can function as a magnetosensor in the magnetoreception system of Drosophila and that it does so in a light-dependent manner. The results show that human CRY2 has the molecular capability to function as a light-sensitive magnetosensor and reopen an area …


Cd4+ Regulatory T Cells Require Ctla-4 For The Maintenance Of Systemic Tolerance, Randall Friedline, David Brown, Hai Nguyen, Hardy Kornfeld, Jinhee Lee, Yi Zhang, Mark Appleby, Sandy Der, Joonsoo Kang, Cynthia Chambers Dec 2015

Cd4+ Regulatory T Cells Require Ctla-4 For The Maintenance Of Systemic Tolerance, Randall Friedline, David Brown, Hai Nguyen, Hardy Kornfeld, Jinhee Lee, Yi Zhang, Mark Appleby, Sandy Der, Joonsoo Kang, Cynthia Chambers

David C. Brown

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3(+) regulatory T cells. CTLA-4-deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4-deficient and -sufficient bone marrow (BM)-derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4(-/-) T cells in trans by CTLA-4-sufficient T cells is …


Defining Behavioral And Molecular Differences Between Summer And Migratory Monarch Butterflies, Haisun Zhu, Robert Gegear, Amy Casselman, Sriramana Kanginakudru, Steven Reppert Dec 2015

Defining Behavioral And Molecular Differences Between Summer And Migratory Monarch Butterflies, Haisun Zhu, Robert Gegear, Amy Casselman, Sriramana Kanginakudru, Steven Reppert

Robert J. Gegear

BACKGROUND: In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. RESULTS: Here we show that increasing juvenile hormone activity to induce summer-like …


Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor Aug 2015

Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor

Janet M. Stavnezer

Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is …


The Fly Camta Transcription Factor Potentiates Deactivation Of Rhodopsin, A G Protein-Coupled Light Receptor, Junhai Han, Ping Gong, Keith Reddig, Mirna Mitra, Peiyi Guo, Hong-Sheng Li Jul 2015

The Fly Camta Transcription Factor Potentiates Deactivation Of Rhodopsin, A G Protein-Coupled Light Receptor, Junhai Han, Ping Gong, Keith Reddig, Mirna Mitra, Peiyi Guo, Hong-Sheng Li

Peiyi Guo

Control of membrane-receptor activity is required not only for the accuracy of sensory responses, but also to protect cells from excitotoxicity. Here we report the isolation of two noncomplementary fly mutants with slow termination of photoresponses. Genetic and electrophysiological analyses of the mutants revealed a defect in the deactivation of rhodopsin, a visual G protein-coupled receptor (GPCR). The mutant gene was identified as the calmodulin-binding transcription activator (dCAMTA). The known rhodopsin regulator Arr2 does not mediate this visual function of dCAMTA. A genome-wide screen identified five dCAMTA target genes. Of these, overexpression of the F box gene dFbxl4 rescued the …


Mutation Of A Tadr Protein Leads To Rhodopsin And Gq-Dependent Retinal Degeneration In Drosophila, Lina Ni, Peiyi Guo, Keith Reddig, Mirna Mitra, Hong-Sheng Li Jul 2015

Mutation Of A Tadr Protein Leads To Rhodopsin And Gq-Dependent Retinal Degeneration In Drosophila, Lina Ni, Peiyi Guo, Keith Reddig, Mirna Mitra, Hong-Sheng Li

Peiyi Guo

The Drosophila photoreceptor is a model system for genetic study of retinal degeneration. Many gene mutations cause fly photoreceptor degeneration, either because of excessive stimulation of the visual transduction (phototransduction) cascade, or through apoptotic pathways that in many cases involve a visual arrestin Arr2. Here we report a gene named tadr (for torn and diminished rhabdomeres), which, when mutated, leads to photoreceptor degeneration through a different mechanism. Degeneration in the tadr mutant is characterized by shrunk and disrupted rhabdomeres, the light sensory organelles of photoreceptor. The TADR protein interacted in vitro with the major light receptor Rh1 rhodopsin, and genetic …


Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong Jun 2015

Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong

Gyongyi Szabo

Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …


Molecular Basis Of Rna Recognition By The Embryonic Polarity Determinant Mex-5, John Pagano, Brian Farley, Lisa Mccoig, Sean Ryder May 2015

Molecular Basis Of Rna Recognition By The Embryonic Polarity Determinant Mex-5, John Pagano, Brian Farley, Lisa Mccoig, Sean Ryder

Sean P. Ryder

Embryonic development requires maternal proteins and RNA. In Caenorhabditis elegans, a gradient of CCCH tandem zinc finger (TZF) proteins coordinates axis polarization and germline differentiation. These proteins govern expression from maternal mRNAs by an unknown mechanism. Here we show that the TZF protein MEX-5, a primary anterior determinant, is an RNA-binding protein that recognizes linear RNA sequences with high affinity but low specificity. The minimal binding site is a tract of six or more uridines within a 9-13-nucleotide window. This sequence is remarkably abundant in the 3'-untranslated region of C. elegans transcripts, demonstrating that MEX-5 alone cannot specify mRNA target …


Rna Target Specificity Of The Embryonic Cell Fate Determinant Pos-1, Brian Farley, John Pagano, Sean Ryder May 2015

Rna Target Specificity Of The Embryonic Cell Fate Determinant Pos-1, Brian Farley, John Pagano, Sean Ryder

Sean P. Ryder

Specification of Caenorhabditis elegans body axes and cell fates occurs prior to the activation of zygotic transcription. Several CCCH-type tandem zinc finger (TZF) proteins coordinate local activation of quiescent maternal mRNAs after fertilization, leading to asymmetric expression of factors required for patterning. The primary determinant of posterior fate is the TZF protein POS-1. Mutants of pos-1 are maternal effect lethal with a terminal phenotype that includes excess pharyngeal tissue and no endoderm or germline. Here, we delineate the consensus POS-1 recognition element (PRE) required for specific recognition of its target mRNAs. The PRE is necessary but not sufficient to pattern …


Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder May 2015

Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder

Sean P. Ryder

Myelin-associated glycoprotein (MAG) is a major component of myelin in the vertebrate central nervous system. MAG is present in the periaxonal region of the myelin structure, where it interacts with neuronal proteins to inhibit axon outgrowth and protect neurons from degeneration. Two alternatively spliced isoforms of Mag mRNA have been identified. The mRNA encoding the shorter isoform, known as S-MAG, contains a termination codon in exon 12, while the mRNA encoding the longer isoform, known as L-MAG, skips exon 12 and produces a protein with a longer C-terminal region. L-MAG is required in the central nervous system. How inclusion of …


Argonaute Protein Identity And Pairing Geometry Determine Cooperativity In Mammalian Rna Silencing, Jennifer Broderick, William Salomon, Sean Ryder, Neil Aronin, Phillip Zamore May 2015

Argonaute Protein Identity And Pairing Geometry Determine Cooperativity In Mammalian Rna Silencing, Jennifer Broderick, William Salomon, Sean Ryder, Neil Aronin, Phillip Zamore

Sean P. Ryder

Small RNAs loaded into Argonaute proteins direct silencing of complementary target mRNAs. It has been proposed that multiple, imperfectly complementary small interfering RNAs or microRNAs, when bound to the 3' untranslated region of a target mRNA, function cooperatively to silence target expression. We report that, in cultured human HeLa cells and mouse embryonic fibroblasts, Argonaute1 (Ago1), Ago3, and Ago4 act cooperatively to silence both perfectly and partially complementary target RNAs bearing multiple small RNA-binding sites. Our data suggest that for Ago1, Ago3, and Ago4, multiple, adjacent small RNA-binding sites facilitate cooperative interactions that stabilize Argonaute binding. In contrast, small RNAs …


Post-Transcriptional Regulation Of Myelin Formation, Nancy Zearfoss, Brian Farley, Sean Ryder May 2015

Post-Transcriptional Regulation Of Myelin Formation, Nancy Zearfoss, Brian Farley, Sean Ryder

Sean P. Ryder

Myelin is a specialized structure of the nervous system that both enhances electrical conductance and protects neurons from degeneration. In the central nervous system, extensively polarized oligodendrocytes form myelin by wrapping cellular processes in a spiral pattern around neuronal axons. Myelin formation requires the oligodendrocyte to regulate gene expression in response to changes in its extracellular environment. Because these changes occur at a distance from the cell body, post-transcriptional control of gene expression allows the cell to fine-tune its response. Here, we review the RNA-binding proteins that control myelin formation in the brain, highlighting the molecular mechanisms by which they …


Sociology And Anthrozoology: Symbolic Interactionist Contributions, Leslie Irvine Apr 2015

Sociology And Anthrozoology: Symbolic Interactionist Contributions, Leslie Irvine

Leslie Irvine, PhD

This essay examines the sociological contributions to anthrozoology, focusing on research from the United States that employs a symbolic interactionist perspective. In particular, the work of Arluke and Sanders highlights the importance of understanding the meanings that animals hold for people. Using a selective review of their research, this essay outlines how a focus on understanding meaning can inform anthrozoological research. Arluke’s research on animal abuse reveals how harm must be defined in context. Sanders’s research on canine–human relationships documents how people come to understand companion dogs as persons. Both bodies of work rely on careful observation and listening to …


The Role Of Tnf-Receptor Family Members And Other Traf-Dependent Receptors In Bone Resorption, Ellen M. Gravallese, Deborah L. Galson, Steven R. Goldring, Philip E. Auron Apr 2015

The Role Of Tnf-Receptor Family Members And Other Traf-Dependent Receptors In Bone Resorption, Ellen M. Gravallese, Deborah L. Galson, Steven R. Goldring, Philip E. Auron

Ellen M. Gravallese

The contribution of osteoclasts to the process of bone loss in inflammatory arthritis has recently been demonstrated. Studies in osteoclast biology have led to the identification of factors responsible for the differentiation and activation of osteoclasts, the most important of which is the receptor activator of NF-kappa B ligand/osteoclast differentiation factor (RANKL/ODF), a tumor necrosis factor (TNF)-like protein. The RANKL/ODF receptor, receptor activator of NF-kappa B (RANK), is a TNF-receptor family member present on both osteoclast precursors and mature osteoclasts. Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting …


Critical Roles For Interleukin 1 And Tumor Necrosis Factor Alpha In Antibody-Induced Arthritis, Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen M. Gravallese, Diane Mathis, Christophe Benoist Apr 2015

Critical Roles For Interleukin 1 And Tumor Necrosis Factor Alpha In Antibody-Induced Arthritis, Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen M. Gravallese, Diane Mathis, Christophe Benoist

Ellen M. Gravallese

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also …


Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger Apr 2015

Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger

Nils Henninger

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated …


A Mutation In The Mouse Chd2 Chromatin Remodeling Enzyme Results In A Complex Renal Phenotype, Concetta Marfella, Nils Henninger, Scott Leblanc, Namrata Krishnan, David Garlick, Lawrence Holzman, Anthony Imbalzano Apr 2015

A Mutation In The Mouse Chd2 Chromatin Remodeling Enzyme Results In A Complex Renal Phenotype, Concetta Marfella, Nils Henninger, Scott Leblanc, Namrata Krishnan, David Garlick, Lawrence Holzman, Anthony Imbalzano

Nils Henninger

BACKGROUND AND AIMS: Glomerular diseases are the third leading cause of kidney failure worldwide, behind only diabetes and hypertension. The molecular mechanisms underlying the cause of glomerular diseases are still largely unknown. The identification and characterization of new molecules associated with glomerular function should provide new insights into understanding the diverse group of glomerular diseases. The Chd2 protein belongs to a family of enzymes involved in ATP-dependent chromatin remodeling, suggesting that it likely functions as an epigenetic regulator of gene expression via the modification of chromatin structure. METHODS: In this study, we present a detailed histomorphologic characterization of mice containing …