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Full-Text Articles in Life Sciences
Interactions Of Deet And Novel Repellents With Mosquito Odorant Receptors, Gariel G. Grant, Rachel R. Estrera, Narendra Pathak, C. Dennis Hall, Maia Tsikolia, Kenneth J. Linthicum, Ulrich R. Bernier, Adam C. Hall
Interactions Of Deet And Novel Repellents With Mosquito Odorant Receptors, Gariel G. Grant, Rachel R. Estrera, Narendra Pathak, C. Dennis Hall, Maia Tsikolia, Kenneth J. Linthicum, Ulrich R. Bernier, Adam C. Hall
Neuroscience: Faculty Publications
The carboxamide N,N-di-ethyl-meta-Toluamide (DEET) is the most effective and widely used insect repellent today. However, drawbacks concerning the efficacy and the safety of the repellent have led to efforts to design new classes of insect repellents. Through quantitative structure-Activity relationships, chemists have discovered two chemical groups of novel repellents: The acylpiperidines and the carboxamides, with the acylpiperidines generally more potent in biological assays. Although the exact mechanism of action of DEET and other repellents has not yet been thoroughly elucidated, previous research shows that the activity of insect odorant receptors are inhibited in the presence of repellents. The present electrophysiological …
Osr1 Is Required For Podocyte Development Downstream Of Wt1a, Ritu Tomar, Sudha P. Mudumana, Narendra Pathak, Neil A. Hukriede, Iain A. Drummond
Osr1 Is Required For Podocyte Development Downstream Of Wt1a, Ritu Tomar, Sudha P. Mudumana, Narendra Pathak, Neil A. Hukriede, Iain A. Drummond
Neuroscience: Faculty Publications
Odd-skipped related 1 (Osr1) encodes a zinc finger transcription factor required for kidney development. Osr1 deficiency in mice results in metanephric kidney agenesis, whereas knockdown or mutation studies in zebrafish revealed that pronephric nephrons require osr1 for proximal tubule and podocyte development. osr1-deficient pronephric podocyte progenitors express the Wilms' tumor suppressor wt1a but do not undergo glomerular morphogenesis or express the foot process junctional markers nephrin and podocin. The function of osr1 in podocyte differentiation remains unclear, however. Here, we found by double fluorescence in situ hybridization that podocyte progenitors coexpress osr1 and wt1a. Knockdown of wt1a disrupted podocyte differentiation …
Cytoplasmic Carboxypeptidase 5 Regulates Tubulin Glutamylation And Zebrafish Cilia Formation And Function, Narendra Pathak, Christina A. Austin-Tse, Yan Liu, Aleksandr Vasilyev, Iain A. Drummond
Cytoplasmic Carboxypeptidase 5 Regulates Tubulin Glutamylation And Zebrafish Cilia Formation And Function, Narendra Pathak, Christina A. Austin-Tse, Yan Liu, Aleksandr Vasilyev, Iain A. Drummond
Neuroscience: Faculty Publications
Glutamylation is a functionally important tubulin posttranslational modification enriched on stable microtubules of neuronal axons, mitotic spindles, centrioles, and cilia. In vertebrates, balanced activities of tubulin glutamyl ligase and cytoplasmic carboxypeptidase deglutamylase enzymes maintain organelle- and cell type-specific tubulin glutamylation pat terns. Tubulin glutamylation in cilia is regulated via restricted subcellular localization or ex pression of tubulin glutamyl ligases (ttlls) and nonenzymatic proteins, including the zebrafish TPR repeat protein Fleer/Ift70. Here we analyze the expression patterns of ccp deglutamy lase genes during zebrafish development and the effects of ccp gene knockdown on cilia formation, morphology, and tubulin glutamylation. The deglutamylases …
Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 And Ccdc65 Defects As Causing Primary Ciliary Dyskinesia, Christina Austin-Tse, Jan Halbritter, Maimoona A. Zariwala, Renée M. Gilberti, Heon Yung Gee, Nathan Hellman, Narendra Pathak, Yan Liu, Jennifer R. Panizzi, Ramila S. Patel-King, Douglas Tritschler, Raqual Bower, Eileen O'Toole, Jonathan D. Porath, Toby W. Hurd, Moumita Chaki, Katrina A. Diaz, Stefan Kohl, Svjetlana Lovric, Daw Yang Hwang, Daniela A. Braun, Markus Schueler, Rannar Airik, Edgar A. Otto, Margaret W. Leigh, Peadar G. Noone, Johnny L. Carson, Stephanie D. Davis, Jessica E. Pittman, Thomas W. Ferkol, Jeffry J. Atkinson, Kenneth N. Olivier
Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 And Ccdc65 Defects As Causing Primary Ciliary Dyskinesia, Christina Austin-Tse, Jan Halbritter, Maimoona A. Zariwala, Renée M. Gilberti, Heon Yung Gee, Nathan Hellman, Narendra Pathak, Yan Liu, Jennifer R. Panizzi, Ramila S. Patel-King, Douglas Tritschler, Raqual Bower, Eileen O'Toole, Jonathan D. Porath, Toby W. Hurd, Moumita Chaki, Katrina A. Diaz, Stefan Kohl, Svjetlana Lovric, Daw Yang Hwang, Daniela A. Braun, Markus Schueler, Rannar Airik, Edgar A. Otto, Margaret W. Leigh, Peadar G. Noone, Johnny L. Carson, Stephanie D. Davis, Jessica E. Pittman, Thomas W. Ferkol, Jeffry J. Atkinson, Kenneth N. Olivier
Neuroscience: Faculty Publications
Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to chronic airway infections, male infertility, and situs abnormalities. Multiple causative PCD mutations account for only 65% of cases, suggesting that many genes essential for cilia function remain to be discovered. By using zebrafish morpholino knockdown of PCD candidate genes as an in vivo screening platform, we identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility. c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is …
Chronic Stress Elevates Telomerase Activity In Rats, Annaliese K. Beery, Jue Lin, Joshua S. Biddle, Darlene D. Francis, Elizabeth H. Blackburn, Elissa S. Epel
Chronic Stress Elevates Telomerase Activity In Rats, Annaliese K. Beery, Jue Lin, Joshua S. Biddle, Darlene D. Francis, Elizabeth H. Blackburn, Elissa S. Epel
Neuroscience: Faculty Publications
The enzyme telomerase lengthens telomeres—protective structures containing repetitive DNA sequences at chromosome ends. Telomere shortening is associated with diseases of ageing in mammals. Chronic stress has been related to shorter immune-cell telomeres, but telomerase activity under stress may be low, permitting telomere loss, or high, partially attenuating it. We developed an experimental model to examine the impacts of extended unpredictable stress on telomerase activity in male rats. Telomerase activity was 54 per cent higher in stressed rats than in controls, and associated with stress-related physiological and behavioural outcomes. This significant increase suggests a potential mechanism for resilience to stress-related replicative …
Mechanical Stretch And Pi3k Signaling Link Cell Migration And Proliferation To Coordinate Epithelial Tubule Morphogenesis In The Zebrafish Pronephros, Aleksandr Vasilyev, Yan Liu, Nathan Hellman, Narendra Pathak, Iain A. Drummond
Mechanical Stretch And Pi3k Signaling Link Cell Migration And Proliferation To Coordinate Epithelial Tubule Morphogenesis In The Zebrafish Pronephros, Aleksandr Vasilyev, Yan Liu, Nathan Hellman, Narendra Pathak, Iain A. Drummond
Neuroscience: Faculty Publications
Organ development leads to the emergence of organ function, which in turn can impact developmental processes. Here we show that fluid flow-induced collective epithelial migration during kidney nephron morphogenesis induces cell stretch that in turn signals epithelial proliferation. Increased cell proliferation was dependent on PI3K signaling. Inhibiting epithelial proliferation by blocking PI3K or CDK4/Cyclin D1 activity arrested cell migration prematurely and caused a marked overstretching of the distal nephron tubule. Computational modeling of the involved cell processes predicted major morphological and kinetic outcomes observed experimentally under a variety of conditions. Overall, our findings suggest that kidney development is a recursive …
Tubulin Tyrosine Ligase-Like Genes Ttll3 And Ttll6 Maintain Zebrafish Cilia Structure And Motility, Narendra Pathak, Christina A. Austin, Iain A. Drummond
Tubulin Tyrosine Ligase-Like Genes Ttll3 And Ttll6 Maintain Zebrafish Cilia Structure And Motility, Narendra Pathak, Christina A. Austin, Iain A. Drummond
Neuroscience: Faculty Publications
Tubulin post-translational modifications generate microtubule heterogeneity and modulate microtubule function, and are catalyzed by tubulin tyrosine ligase-like (TTLL) proteins. Using antibodies specific to monoglycylated, polyglycylated, and glutamylated tubulin in whole mount immunostaining of zebrafish embryos, we observed distinct, tissue-specific patterns of tubulin modifications. Tubulin modification patterns in cilia correlated with the expression of ttll3 and ttll6 in ciliated cells. Expression screening of all zebrafish tubulin tyrosine ligase-like genes revealed additional tissue-specific expression of ttll1 in brain neurons, ttll4 in muscle, and ttll7 in otic placodes. Knockdown of ttll3 eliminated cilia tubulin glycylation but had surprisingly mild effects on cilia structure …
The Homodimeric Kinesin, Kif17, Is Essential For Vertebrate Photoreceptor Sensory Outer Segment Development, Christine Insinna, Narendra Pathak, Brian Perkins, Iain Drummond, Joseph C. Besharse
The Homodimeric Kinesin, Kif17, Is Essential For Vertebrate Photoreceptor Sensory Outer Segment Development, Christine Insinna, Narendra Pathak, Brian Perkins, Iain Drummond, Joseph C. Besharse
Neuroscience: Faculty Publications
Sensory cilia and intraflagellar transport (IFT), a pathway essential for ciliogenesis, play important roles in embryonic development and cell differentiation. In vertebrate photoreceptors IFT is required for the early development of ciliated sensory outer segments (OS), an elaborate organelle that sequesters the many proteins comprising the phototransduction machinery. As in other cilia and flagella, heterotrimeric members of the kinesin 2 family have been implicated as the anterograde IFT motor in OS. However, in Caenorhabditis elegans, OSM-3, a homodimeric kinesin 2 motor, plays an essential role in some, but not all sensory cilia. Kif17, a vertebrate OSM-3 homologue, is known for …
The Zebrafish Fleer Gene Encodes An Essential Regulator Of Cilia Tubulin Polyglutamylation, Narendra Pathak, Tomoko Obara, Steve Mangos, Yan Liu, Iain A. Drummond
The Zebrafish Fleer Gene Encodes An Essential Regulator Of Cilia Tubulin Polyglutamylation, Narendra Pathak, Tomoko Obara, Steve Mangos, Yan Liu, Iain A. Drummond
Neuroscience: Faculty Publications
Cilia and basal bodies are essential organelles for a broad spectrum of functions, including the development of left-right asymmetry, kidney function, cerebrospinal fluid transport, generation of photoreceptor outer segments, and hedgehog signaling. Zebrafish fleer (flr) mutants exhibit kidney cysts, randomized left-right asymmetry, hydrocephalus, and rod outer segment defects, suggesting a pleiotropic defect in ciliogenesis. Positional cloning flr identified a tetratricopeptide repeat protein homologous to the Caenorhabditis elegans protein DYF1 that was highly expressed in ciliated cells, flr pronephric cilia were shortened and showed a reduced beat amplitude, and olfactory cilia were absent in mutants, flr cilia exhibited ultrastructural defects in …
Notch Signaling Controls The Differentiation Of Transporting Epithelia And Multiciliated Cells In The Zebrafish Pronephros, Yan Liu, Narendra Pathak, Albrecht Kramer-Zucker, Iain A. Drummond
Notch Signaling Controls The Differentiation Of Transporting Epithelia And Multiciliated Cells In The Zebrafish Pronephros, Yan Liu, Narendra Pathak, Albrecht Kramer-Zucker, Iain A. Drummond
Neuroscience: Faculty Publications
Epithelial tubules consist of multiple cell types that are specialized for specific aspects of organ function. In the zebrafish pronephros, multiciliated cells (MCCs) are specialized for fluid propulsion, whereas transporting epithelial cells recover filtered-blood solutes. These cell types are distributed in a 'salt-and-pepper' fashion in the pronephros, suggesting that a lateral inhibition mechanism may play a role in their differentiation. We find that the Notch ligand Jagged 2 is expressed in MCCs and that notch3 is expressed in pronephric epithelial cells. Morpholino knockdown of either jagged 2 or notch3, or mutation in mind bomb (in which Notch signaling is impaired), …