33 results on '"Woodson M"'
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2. The Issue of Item and Test Variance for Criterion-Referenced Tests.
- Author
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Woodson, M. I. Charles E.
- Abstract
It has been argued that item variance and test variance are not necessary characteristics for criterion-referenced tests, although they are necessary for norm-referenced tests. This position is in error because it considers sample statistics as the criteria for evaluating items and tests. Within a particular sample, an item or test may have no variance, but in the population for which the test was designed and evaluated, both items and tests must have variance. (Author)
3. Classical Test Theory and Criterion-Referenced Scales.
- Author
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Woodson, M. I. Charles E.
- Abstract
The item (difficulty and discrimination) and test (reliability and validity) statistics in classical test theory are highly dependent upon the calibration sample of individuals used. The estimates of item and test parameters in classical test theory is valid within a range of interest along the characteristic measured. Generally, this range of interest is the distribution of the characteristic in some population, and the calibration sample used is intended to be a random sample from that population. In such populations, the extremes usually are poorly represented, and the parameter estimates are relatively poor at these extremes. For criterion-referenced scales, the range of interest is defined by a range of the characteristic rather than the distribution of that characteristic in some population. The calibration sample must be representative of that range of interest. When the range of interest is appropriately defined, an appropriate calibration sample may be selected, and classical test theory applies directly to criterion-referenced scales. (Author/DB)
4. Migrations in Late Anasazi Prehistory: The Evidence from the Goat Hill Site
- Author
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Woodson, M. Kyle
- Published
- 1999
5. Truncorotaloides danvillensis (Howe and Wallace), New Generic Assignment for a Late Eocene Planktonic Species of Foraminiferida
- Author
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Godfrey, Woodson M. and Van Den Bold, Willem A.
- Published
- 1986
6. Focused Ion Beam Milled Nanochannels for Confinement Enabled DNA Single-Molecule Studies
- Author
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Menard, L., primary, Zhou, J., additional, Woodson, M., additional, Mair, C., additional, Alarie, J., additional, and Ramsey, J., additional
- Published
- 2012
- Full Text
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7. Water-Mass Effects and Sequence Boundaries in the Late Miocene of the Gulf of Mexico
- Author
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Woodson M. Godfrey
- Published
- 1996
8. Truncorotaloides danvillensis (Howe and Wallace), new generic assignment for a Late Eocene planktonic species of Foraminiferida
- Author
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Willem Aaldert van den Bold and Woodson M. Godfrey
- Subjects
Paleontology ,Ecology ,Plankton ,Biology - Abstract
Globorotalia danvillensis was described by Howe and Wallace (1932) from beds at Danville Landing on the Ouachita River, Louisiana. Fisk (1938) gave these beds formational status, because he considered them to be a mappable unit, representing the uppermost Eocene deposits in Louisiana. These beds are placed in the Globorotalia cerroazulensis s.l. Zone. Globorotalia danvillensis was later reported by Bergquist (in Bergquist and McCutcheon, 1942) from upper Eocene beds in Mississippi. The present authors have found the same species in beds of the Lower Jackson Group at Montgomery Landing, Louisiana, which include the upper part of the Porticulasphaera semiinvoluta Zone and the lower part of the Globorotalia cerroazulensis Zone. During the investigation it was found that the species exhibits small, secondary, sutural apertures on the spiral side, which places it in the genus Truncorotaloides Brönnimann and Bermúdez (1953). Howe (1939), in his study of the Cook Mountain foraminifera, followed the custom of that time (see Cushman and Dusenbury, 1934, p. 63) of tentatively referring small coiled species of planktonic foraminifera to Globigerina cretacea d'Orbigny. Re-examination of samples from the Cook Mountain Formation of Saline Bayou, Winn Parish, Louisiana (H. V. Howe collection M 524–527) reveals that many of Howe's specimens belong to Truncorotaloides danvillensis. This species occurs here together with T. rohri Brönnimann and Bermúdez.
- Published
- 1986
9. THE ISSUE OF ITEM AND TEST VARIANCE FOR CRITERION-REFERENCED TESTS: A REPLY
- Author
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WOODSON, M. I. CHAS. E., primary
- Published
- 1974
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10. Parameter Estimation vs. Hypothesis Testing
- Author
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Woodson, M. I. Charles E., primary
- Published
- 1969
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11. Reviews: Dayton, C. Mitchell. The Design of Educational Experiments. New York: McGraw-Hill, 1970. 441 + xi pp. $10.50.
- Author
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Woodson, M. I. Chas. E., primary
- Published
- 1971
- Full Text
- View/download PDF
12. The Design of Educational Experiments.
- Author
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Woodson, M. I. Chas E.
- Subjects
EDUCATION ,NONFICTION - Abstract
Reviews the book "The Design of Educational Experiments," by C. Mitchell Dayton.
- Published
- 1971
- Full Text
- View/download PDF
13. Biophysical and structural characterization of a multifunctional viral genome packaging motor.
- Author
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Prokhorov NS, Davis CR, Maruthi K, Yang Q, Sherman MB, Woodson M, White MA, Miller LM, Jarrold MF, Catalano CE, and Morais MC
- Subjects
- Bacteriophage lambda genetics, Endodeoxyribonucleases metabolism, DNA, DNA, Viral metabolism, DNA Packaging, Viral Genome Packaging, Virus Assembly genetics
- Abstract
The large dsDNA viruses replicate their DNA as concatemers consisting of multiple covalently linked genomes. Genome packaging is catalyzed by a terminase enzyme that excises individual genomes from concatemers and packages them into preassembled procapsids. These disparate tasks are catalyzed by terminase alternating between two distinct states-a stable nuclease that excises individual genomes and a dynamic motor that translocates DNA into the procapsid. It was proposed that bacteriophage λ terminase assembles as an anti-parallel dimer-of-dimers nuclease complex at the packaging initiation site. In contrast, all characterized packaging motors are composed of five terminase subunits bound to the procapsid in a parallel orientation. Here, we describe biophysical and structural characterization of the λ holoenzyme complex assembled in solution. Analytical ultracentrifugation, small angle X-ray scattering, and native mass spectrometry indicate that 5 subunits assemble a cone-shaped terminase complex. Classification of cryoEM images reveals starfish-like rings with skewed pentameric symmetry and one special subunit. We propose a model wherein nuclease domains of two subunits alternate between a dimeric head-to-head arrangement for genome maturation and a fully parallel arrangement during genome packaging. Given that genome packaging is strongly conserved in both prokaryotic and eukaryotic viruses, the results have broad biological implications., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2024
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14. Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors via click-chemistry-based rapid screening.
- Author
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Jiang X, Li J, Viayna A, Luque FJ, Woodson M, Jing L, Gao S, Zhao F, Xie M, Toth K, Tavis J, Tollefson AE, Liu X, and Zhan P
- Abstract
SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro ) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The N -substituted isatin derivative L-26 is a potential SARS-CoV-2 3CLpro inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using click-chemistry-based miniaturized synthesis and their 3CLpro inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay. Compounds D1N8 (IC50 = 0.44 ± 0.12 μM) and D1N52 (IC50 = 0.53 ± 0.21 μM) displayed excellent inhibitory potency against SARS-CoV-2 3CLpro , being equivalent to that of L-26 (IC50 = 0.30 ± 0.14 μM). In addition, the cytotoxicity of D1N8 (CC50 >20 μM) and D1N52 (CC50 >20 μM) decreased significantly compared with L-26 (CC50 <2.6 μM). Further molecular dynamics simulations revealed the potential binding interactions between D1N52 and SARS-CoV-2 3CLpro . These efforts lay a solid foundation for the research of novel anti-SARS-CoV-2 agents targeting 3CLpro ., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)- Published
- 2023
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15. A viral genome packaging motor transitions between cyclic and helical symmetry to translocate dsDNA.
- Author
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Woodson M, Pajak J, Mahler BP, Zhao W, Zhang W, Arya G, White MA, Jardine PJ, and Morais MC
- Subjects
- DNA, Viral chemistry, Genome, Viral, Viral Proteins chemistry, Virus Assembly, DNA Packaging, Viral Genome Packaging
- Abstract
Molecular segregation and biopolymer manipulation require the action of molecular motors to do work by applying directional forces to macromolecules. The additional strand conserved E (ASCE) ring motors are an ancient family of molecular motors responsible for diverse biological polymer manipulation tasks. Viruses use ASCE segregation motors to package their genomes into their protein capsids and provide accessible experimental systems due to their relative simplicity. We show by cryo-EM-focused image reconstruction that ASCE ATPases in viral double-stranded DNA (dsDNA) packaging motors adopt helical symmetry complementary to their dsDNA substrates. Together with previous data, our results suggest that these motors cycle between helical and planar configurations, providing a possible mechanism for directional translocation of DNA. Similar changes in quaternary structure have been observed for proteasome and helicase motors, suggesting an ancient and common mechanism of force generation that has been adapted for specific tasks over the course of evolution., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2021
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16. Towards high-power, high-coherence, integrated photonic mmWave platform with microcavity solitons.
- Author
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Wang B, Morgan JS, Sun K, Jahanbozorgi M, Yang Z, Woodson M, Estrella S, Beling A, and Yi X
- Abstract
Millimetre-wave (mmWave) technology continues to draw great interest due to its broad applications in wireless communications, radar, and spectroscopy. Compared to pure electronic solutions, photonic-based mmWave generation provides wide bandwidth, low power dissipation, and remoting through low-loss fibres. However, at high frequencies, two major challenges exist for the photonic system: the power roll-off of the photodiode, and the large signal linewidth derived directly from the lasers. Here, we demonstrate a new photonic mmWave platform combining integrated microresonator solitons and high-speed photodiodes to address the challenges in both power and coherence. The solitons, being inherently mode-locked, are measured to provide 5.8 dB additional gain through constructive interference among mmWave beatnotes, and the absolute mmWave power approaches the theoretical limit of conventional heterodyne detection at 100 GHz. In our free-running system, the soliton is capable of reducing the mmWave linewidth by two orders of magnitude from that of the pump laser. Our work leverages microresonator solitons and high-speed modified uni-traveling carrier photodiodes to provide a viable path to chip-scale, high-power, low-noise, high-frequency sources for mmWave applications.
- Published
- 2021
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17. Effects of Model Shape, Volume, and Softness of the Capsid for DNA Packaging of phi29.
- Author
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Bores C, Woodson M, Morais MC, and Pettitt BM
- Subjects
- Capsid Proteins genetics, Nucleic Acid Conformation, Bacillus Phages genetics, Capsid, DNA Packaging, DNA, Viral genetics
- Abstract
Double-stranded DNA is under extreme confinement when packed in phage phi29 with osmotic pressures approaching 60 atm and densities near liquid crystalline. The shape of the capsid determined from experiment is elongated. We consider the effects of the capsid shape and volume on the DNA distribution. We propose simple models for the capsid of phage phi29 to capture volume, shape, and wall flexibility, leading to an accurate DNA density profile. The effect of the packaging motor twisting the DNA on the resulting density distribution has been explored. We find packing motor induced twisting leads to a greater numbers of defects formed. The emergence of defects such as bubbles or large roll angles along the DNA shows a sequence dependence, and the resulting flexibility leads to an inhomogeneous distribution of defects occurring more often at TpA steps and AT-rich regions. In conjunction with capsid elongation, this has effects on the global DNA packing structures.
- Published
- 2020
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18. Envelope protein ubiquitination drives entry and pathogenesis of Zika virus.
- Author
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Giraldo MI, Xia H, Aguilera-Aguirre L, Hage A, van Tol S, Shan C, Xie X, Sturdevant GL, Robertson SJ, McNally KL, Meade-White K, Azar SR, Rossi SL, Maury W, Woodson M, Ramage H, Johnson JR, Krogan NJ, Morais MC, Best SM, Shi PY, and Rajsbaum R
- Subjects
- Animals, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Brain metabolism, Cell Line, Culicidae cytology, Culicidae virology, Endosomes metabolism, Female, Hepatitis A Virus Cellular Receptor 1 metabolism, Humans, Male, Membrane Fusion, Mice, Organ Specificity, Polyubiquitin immunology, Polyubiquitin metabolism, Tripartite Motif Proteins metabolism, Ubiquitin-Protein Ligases metabolism, Viral Tropism, Viremia immunology, Viremia prevention & control, Viremia virology, Virus Replication, Zika Virus chemistry, Zika Virus genetics, Zika Virus Infection prevention & control, Zika Virus Infection virology, Ubiquitination, Viral Envelope Proteins chemistry, Viral Envelope Proteins metabolism, Virus Internalization, Zika Virus metabolism, Zika Virus pathogenicity
- Abstract
Zika virus (ZIKV) belongs to the family Flaviviridae, and is related to other viruses that cause human diseases. Unlike other flaviviruses, ZIKV infection can cause congenital neurological disorders and replicates efficiently in reproductive tissues
1-3 . Here we show that the envelope protein (E) of ZIKV is polyubiquitinated by the E3 ubiquitin ligase TRIM7 through Lys63 (K63)-linked polyubiquitination. Accordingly, ZIKV replicates less efficiently in the brain and reproductive tissues of Trim7-/- mice. Ubiquitinated E is present on infectious virions of ZIKV when they are released from specific cell types, and enhances virus attachment and entry into cells. Specifically, K63-linked polyubiquitin chains directly interact with the TIM1 (also known as HAVCR1) receptor of host cells, which enhances virus entry in cells as well as in brain tissue in vivo. Recombinant ZIKV mutants that lack ubiquitination are attenuated in human cells and in wild-type mice, but not in live mosquitoes. Monoclonal antibodies against K63-linked polyubiquitin specifically neutralize ZIKV and reduce viraemia in mice. Our results demonstrate that the ubiquitination of ZIKV E is an important determinant of virus entry, tropism and pathogenesis.- Published
- 2020
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19. Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick-Human Skin Interface.
- Author
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Zhou W, Tahir F, Wang JC, Woodson M, Sherman MB, Karim S, Neelakanta G, and Sultana H
- Abstract
Ticks secrete various anti-coagulatory, anti-vasoconstrictory, anti-inflammatory, and anti-platelet aggregation factors in their saliva at the bite site during feeding to evade host immunological surveillance and responses. For the first time, we report successful isolation of exosomes (small membrane-bound extracellular signaling vesicles) from saliva and salivary glands of partially fed or unfed ixodid ticks. Our data showed a novel role of these in vivo exosomes in the inhibition of wound healing via downregulation of C-X-C motif chemokine ligand 12 (CXCL12) and upregulation of interleukin-8 (IL-8). Cryo-electron microscopy (cryo-EM) analysis revealed that tick saliva and salivary glands are composed of heterogeneous populations of in vivo exosomes with sizes ranging from 30 to 200 nm. Enriched amounts of tick CD63 ortholog protein and heat shock protein 70 (HSP70) were evident in these exosomes. Treatment of human skin keratinocytes (HaCaT cells) with exosomes derived from tick saliva/salivary glands or ISE6 cells dramatically delayed cell migration, wound healing, and repair process. Wound healing is a highly dynamic process with several individualized processes including secretion of cytokines. Cytokine array profiling followed by immunoblotting and quantitative-PCR analysis revealed that HaCaT cells treated with exosomes derived from tick saliva/salivary glands or ISE6 cells showed enhanced IL-8 levels and reduced CXCL12 loads. Inhibition of IL-8 or CXCL12 further delayed exosome-mediated cell migration, wound healing, and repair process, suggesting a skin barrier protection role for these chemokines at the tick bite site. In contrast, exogenous treatment of CXCL12 protein completely restored this delay and enhanced the repair process. Taken together, our study provides novel insights on how tick salivary exosomes secreted in saliva can delay wound healing at the bite site to facilitate successful blood feeding., (Copyright © 2020 Zhou, Tahir, Wang, Woodson, Sherman, Karim, Neelakanta and Sultana.)
- Published
- 2020
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20. Membrane binding and rearrangement by chikungunya virus capping enzyme nsP1.
- Author
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Gottipati K, Woodson M, and Choi KH
- Subjects
- Amino Acid Sequence, Cell Membrane, Cryoelectron Microscopy, Escherichia coli, Gene Expression Regulation, Viral, Lipid Bilayers, Protein Conformation, Protein Folding, Viral Nonstructural Proteins chemistry, Chikungunya virus physiology, Viral Nonstructural Proteins metabolism, Virus Attachment
- Abstract
Alphavirus genome replication is carried out by the viral replication complex inside modified membrane structures called spherules. The viral nonstructural protein 1 (nsP1) is the only membrane-associated protein that anchors the replication complex to the cellular membranes. Although an internal amphipathic helix of nsP1 is critical for membrane association, the mechanism of nsP1 interaction with membranes and subsequent membrane reorganization is not well understood. We studied the membrane interaction of chikungunya virus (CHIKV) nsP1 and show that both the CHIKV nsP1 protein and the amphipathic peptide specifically bind to negatively charged phospholipid vesicles. Using cryo-electron microscopy, we further show that nsP1 forms a contiguous coat on lipid vesicles and induces structural reorganization, while the amphipathic peptide alone failed to deform the membrane bilayer. This suggests that although amphipathic helix of nsP1 is required for initial membrane binding, the remaining cytoplasmic domain of nsP1 is involved in the subsequent membrane reorganization., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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21. Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons.
- Author
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Zhou W, Woodson M, Sherman MB, Neelakanta G, and Sultana H
- Subjects
- Aniline Compounds pharmacology, Animals, Benzylidene Compounds pharmacology, Cells, Cultured, Cerebral Cortex cytology, Cryoelectron Microscopy, Exosomes genetics, Exosomes metabolism, Gene Expression Regulation, Enzymologic, Mice, Neurons cytology, Neurons virology, Time Factors, Viral Load drug effects, Virus Assembly drug effects, Cerebral Cortex virology, Exosomes virology, Sphingomyelin Phosphodiesterase genetics, Sphingomyelin Phosphodiesterase metabolism, Zika Virus physiology
- Abstract
The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barré syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both ZIKV viral RNA and protein(s) that were highly infectious to naïve cells. RNaseA and neutralizing antibodies treatment studies suggest the presence of viral RNA/proteins inside exosomes. Exosomes derived from time- and dose-dependent incubations showed increasing viral loads suggesting higher packaging and delivery of ZIKV RNA and proteins. Furthermore, we noted that ZIKV induced both activity and gene expression of neutral Sphingomyelinase (nSMase)-2/SMPD3, an important molecule that regulates production and release of exosomes. Silencing of SMPD3 in neurons resulted in reduced viral burden and transmission through exosomes. Treatment with SMPD3 specific inhibitor GW4869, significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells. Taken together, our results suggest that ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains.
- Published
- 2019
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22. Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb.
- Author
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Vora A, Zhou W, Londono-Renteria B, Woodson M, Sherman MB, Colpitts TM, Neelakanta G, and Sultana H
- Subjects
- Aedes, Animals, Cell Line, Human Umbilical Vein Endothelial Cells, Humans, Mice, Protein Domains, Dengue genetics, Dengue metabolism, Dengue transmission, Dengue Virus genetics, Dengue Virus metabolism, Dengue Virus pathogenicity, Extracellular Vesicles genetics, Extracellular Vesicles metabolism, Extracellular Vesicles virology, Insect Proteins genetics, Insect Proteins metabolism, Viral Envelope Proteins genetics, Viral Envelope Proteins metabolism
- Abstract
Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and Aedes aegypti , the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naïve mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2-RNA and proteins are contained inside EVs. Viral plaque formation and dilution assays also showed securely contained infectious viral RNA and proteins in EVs are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no role in viral replication and transmission through EVs. In addition, qRT-PCR and immunoblotting results revealed that DENV2 up-regulates expression of a mosquito tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in A. aegypti mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs. Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein. Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission of viral RNA and proteins to naïve human cells. In summary, we report a very important finding on EV-mediated transmission of DENV2 from arthropod to mammalian cells through interactions with an arthropod EVs-enriched marker Tsp29Fb., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
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23. Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells.
- Author
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Zhou W, Woodson M, Neupane B, Bai F, Sherman MB, Choi KH, Neelakanta G, and Sultana H
- Subjects
- Animals, Arthropod Vectors cytology, Arthropod Vectors ultrastructure, Arthropod Vectors virology, Cell Line, Cells, Cultured, Cerebral Cortex cytology, Cerebral Cortex pathology, Cerebral Cortex ultrastructure, Cerebral Cortex virology, Chlorocebus aethiops, Coculture Techniques, Cryoelectron Microscopy, Embryo, Mammalian cytology, Encephalitis Viruses, Tick-Borne physiology, Encephalitis Viruses, Tick-Borne ultrastructure, Encephalitis, Tick-Borne pathology, Encephalitis, Tick-Borne virology, Endothelium, Vascular cytology, Endothelium, Vascular pathology, Endothelium, Vascular ultrastructure, Endothelium, Vascular virology, Exosomes ultrastructure, Host-Parasite Interactions, Host-Pathogen Interactions, Humans, Ixodes cytology, Ixodes ultrastructure, Ixodes virology, Keratinocytes cytology, Keratinocytes pathology, Keratinocytes ultrastructure, Keratinocytes virology, Mice, Mice, Inbred C57BL, Neurons cytology, Neurons pathology, Neurons ultrastructure, Encephalitis Viruses, Tick-Borne pathogenicity, Encephalitis, Tick-Borne transmission, Exosomes virology, Models, Biological, Neurons virology, RNA, Viral metabolism, Viral Proteins metabolism
- Abstract
Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes with the size range of 30 to 200 nm in diameter. Both positive and negative strands of LGTV RNA and viral envelope-protein were detected inside exosomes derived from arthropod, murine and human cells. Detection of Nonstructural 1 (NS1) protein in arthropod and neuronal exosomes further suggested that exosomes contain viral proteins. Viral RNA and proteins in exosomes derived from tick and mammalian cells were secured, highly infectious and replicative in all tested evaluations. Treatment with GW4869, a selective inhibitor that blocks exosome release affected LGTV loads in both arthropod and mammalian cell-derived exosomes. Transwell-migration assays showed that exosomes derived from infected-brain-microvascular endothelial cells (that constitute the blood-brain barrier) facilitated LGTV RNA and protein transmission, crossing of the barriers and infection of neuronal cells. Neuronal infection showed abundant loads of both tick-borne LGTV and mosquito-borne West Nile virus RNA in exosomes. Our data also suggest that exosome-mediated LGTV viral transmission is clathrin-dependent. Collectively, our results suggest that flaviviruses uses arthropod-derived exosomes as a novel means for viral RNA and protein transmission from the vector, and the vertebrate exosomes for dissemination within the host that may subsequently allow neuroinvasion and neuropathogenesis.
- Published
- 2018
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24. Correction: Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.
- Author
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Barber KR, Tanquary J, Bush K, Shaw A, Woodson M, Tangavelou K, Sherman M, and Wairkar YP
- Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1006621.].
- Published
- 2017
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25. Sirt6 deficiency results in progression of glomerular injury in the kidney.
- Author
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Huang W, Liu H, Zhu S, Woodson M, Liu R, Tilton RG, Miller JD, and Zhang W
- Subjects
- Animals, Disease Progression, Kidney Diseases pathology, Kidney Glomerulus metabolism, Mice, Mice, Knockout, Aging pathology, Kidney Diseases metabolism, Kidney Glomerulus pathology, Sirtuins metabolism
- Abstract
Aging is associated with an increased incidence and prevalence of renal glomerular diseases. Sirtuin (Sirt) 6, a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, has been shown to protect against multiple age-associated phenotypes; however it is unknown whether Sirt6 has a direct pathophysiologic role in the kidney. In the present study, we demonstrate that Sirt6 is expressed in the kidney and aging Sirt6-deficient mice exhibit renal hypertrophy with glomerular enlargement. Sirt6 deletion induces podocyte injury, including decreases in slit diaphragm proteins, foot process effacement, and cellular loss, resulting in proteinuria. Knockdown of Sirt6 in cultured primary murine podocytes induces shape changes with loss of process formation and cell apoptosis. Moreover, Sirt6 deficiency results in progressive renal inflammation and fibrosis. Collectively, these data provide compelling evidence that Sirt6 is important for podocyte homeostasis and maintenance of glomerular function, and warrant further investigation into the role of Sirt6 in age-associated kidney dysfunction.
- Published
- 2017
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26. Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.
- Author
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Barber KR, Tanquary J, Bush K, Shaw A, Woodson M, Sherman M, and Wairkar YP
- Subjects
- Animals, Autism Spectrum Disorder pathology, Axons metabolism, Drosophila, Drosophila Proteins metabolism, Glycogen Synthase Kinase 3 metabolism, Humans, Neurons metabolism, Neurons pathology, Presynaptic Terminals metabolism, Presynaptic Terminals pathology, Protein Transport genetics, Synapses genetics, Synapses pathology, Synaptic Transmission genetics, Autism Spectrum Disorder genetics, Drosophila Proteins genetics, Glycogen Synthase Kinase 3 genetics, Neuromuscular Junction genetics, tau Proteins genetics
- Abstract
Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated.
- Published
- 2017
- Full Text
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27. Structural and Molecular Basis for Coordination in a Viral DNA Packaging Motor.
- Author
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Mao H, Saha M, Reyes-Aldrete E, Sherman MB, Woodson M, Atz R, Grimes S, Jardine PJ, and Morais MC
- Subjects
- Adenosine Triphosphatases genetics, Adenosine Triphosphatases metabolism, Adenosine Triphosphate chemistry, Arginine chemistry, Bacillus Phages genetics, Bacillus Phages metabolism, Bacillus subtilis virology, Capsid metabolism, Capsid ultrastructure, Cryoelectron Microscopy, Crystallography, X-Ray, DNA genetics, DNA metabolism, DNA Packaging, DNA, Viral genetics, DNA, Viral metabolism, Gene Expression, Hydrolysis, Models, Molecular, Protein Domains, Protein Structure, Secondary, Protein Subunits genetics, Protein Subunits metabolism, Viral Proteins genetics, Viral Proteins metabolism, Virus Assembly, Adenosine Triphosphatases chemistry, Bacillus Phages ultrastructure, DNA chemistry, DNA, Viral chemistry, Protein Subunits chemistry, Viral Proteins chemistry
- Abstract
Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA packaging motor in bacteriophage phi29 show how individual subunits are arranged in a pentameric ATPase ring and suggest how their activities are coordinated to translocate dsDNA. The resulting pseudo-atomic structure of the motor and accompanying functional analyses show how ATP is bound in the ATPase active site; identify two DNA contacts, including a potential DNA translocating loop; demonstrate that a trans-acting arginine finger is involved in coordinating hydrolysis around the ring; and suggest a functional coupling between the arginine finger and the DNA translocating loop. The ability to visualize the motor in action illuminates how the different motor components interact with each other and with their DNA substrate., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
28. Histological evidence of oxidative stress and premature senescence in preterm premature rupture of the human fetal membranes recapitulated in vitro.
- Author
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Menon R, Boldogh I, Hawkins HK, Woodson M, Polettini J, Syed TA, Fortunato SJ, Saade GR, Papaconstantinou J, and Taylor RN
- Subjects
- Biomarkers metabolism, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Extraembryonic Membranes pathology, Female, Fetal Membranes, Premature Rupture pathology, Humans, Pregnancy, Premature Birth pathology, Tumor Suppressor Protein p53 metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Extraembryonic Membranes metabolism, Fetal Membranes, Premature Rupture metabolism, Oxidative Stress, Premature Birth metabolism
- Abstract
Preterm prelabor rupture of the membranes (pPROM) may lead to preterm births (PTBs). We investigated premature senescence of fetal membranes in women with pPROM and spontaneous PTB with intact membranes (<34 weeks) and the inducibility fetal membrane senescence phenotype by oxidative stress in vitro. IHC was performed for p53, p21, and phospho (p)-p38 mitogen-activated protein kinase (MAPK) as markers of senescence phenotype in pPROM, PTBs, and term births. Term fetal membranes were exposed to cigarette smoke extract to induce oxidative stress. Western blots documented p-p53 and p-p38 MAPK. Transmission electron microscopy assessed cellular morphologic features in clinical and cigarette smoke extract-treated membranes. A total of 80% of pPROM cells and >60% of term cells were positive for all three senescence phenotype markers, and concentrations were higher than in PTBs (P < 0.05). p53 staining was comparable in membranes from PTB and term birth pregnancies, whereas only <30% and <45% of cells were positive for p21 and p38 MAPK, respectively. In vitro cigarette smoke extract exposure increased p-p38 MAPK without any detectable change in p-p53 MAPK. Enlargement of organelles consistent with senescence phenotype was evident in pPROM and term membranes in vivo and after cigarette smoke extract treatment in vitro but was less apparent in PTBs. Histologic and biochemical resemblance of pPROM and term membranes suggests premature senescence of the membranes is a mechanistic feature in pPROM, and this can be phenocopied in an in vitro model., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
29. Composite training images for synthetic discriminant functions.
- Author
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Brasher JD and Woodson M
- Abstract
The use of composite images allows more images to be included in the construction of synthetic discriminant functions without increasing the training-set cardinality. This provides lower computational overhead or allows inclusion of more training information for the same computational load. The procedure is demonstrated with the minimum-average-correlation-energy synthetic discriminant function as an example.
- Published
- 1996
- Full Text
- View/download PDF
30. Gelatinolytic and caseinolytic proteinase activities in the secretions of the ventral, lateral, and dorsal lobes of the rat prostate.
- Author
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Wilson MJ, Garcia B, Woodson M, and Sinha AA
- Subjects
- Animals, Calcium pharmacology, Endopeptidases chemistry, Male, Molecular Weight, Prostate metabolism, Rats, Rats, Sprague-Dawley, Caseins metabolism, Endopeptidases metabolism, Gelatin metabolism, Prostate enzymology
- Abstract
The ventral, lateral, and dorsal lobes of the rat prostate produce secretions rich in protein. We examined these secretions for proteinase activities, using gelatin- and casein-containing SDS-polyacrylamide gel zymographies. The ventral lobe demonstrated both higher activities and more molecular forms of proteinase activities that cleaved these two protein substrates than did the other lobes. Ca(2+)-stimulated gelatinolytic activities of approximately 48, 51, 58, 64, 74, and 80 kDa were found in ventral prostate secretions in addition to activities detected in the absence of added Ca2+: a very strong 27-kDa activity; prominent 22-, 86-, 90-, and 94-kDa activities; and less active 36-, 41-, 100-, 130-, and 140-kDa activities. Ca(2+)-stimulated gelatinolytic activities of 51, 58, 74, 80, 86, 90, and 94 kDa were present in lateral prostate secretions (none were detected in secretions of the dorsal lobe), and Ca(2+)-independent activities of 25, 27, and 100 kDa were found in secretions of both the lateral and dorsal lobes. The Ca(2+)-stimulated activities were inhibited by EGTA and EDTA. Benzamidine inhibited all gelatinolytic activities except for the 22-, 25-, and 27-kDa Ca(2+)-independent forms when Ca2+ was not added to the reaction buffer. However, in the presence of 5 mM CaCl2, the Ca(2+)-stimulated forms of proteinase were unaffected by benzamidine, whereas the other activities sensitive to benzamidine were inhibited. Prominent Ca(2+)-independent caseinolytic activities of 20, 23, 31, 37, 83, 89, and 94 kDa were detected in ventral lobe secretions along with less active forms of about 39, 48, 53, 57, 60, 63, 80, 103, 110, 125, and 160 kDa. Caseinolytic activities of approximately 23, 31, 53, 89, 94, 103, 120, and 125 kDa were found in lateral prostate secretions, and 89, 94, and 103 kDa activities were found in secretions of the dorsal lobe. Quantitatively, most gelatinolytic and caseinolytic activities were present in the soluble portion of the secretion of each prostatic lobe. The ventral, lateral, and dorsal prostate lobes all secrete gelatinolytic and caseinolytic proteinase activities; however, quantitatively the ventral lobe is the most notable in this function since its secretions contain more molecular forms and greater activities of these proteinases.
- Published
- 1993
- Full Text
- View/download PDF
31. Metalloproteinase activities expressed during development and maturation of the rat prostatic complex and seminal vesicles.
- Author
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Wilson MJ, Garcia B, Woodson M, and Sinha AA
- Subjects
- Animals, Animals, Newborn, Barium pharmacology, Calcium pharmacology, Caseins metabolism, Cobalt pharmacology, Edetic Acid pharmacology, Egtazic Acid pharmacology, Electrophoresis, Polyacrylamide Gel, Gene Expression Regulation, Enzymologic drug effects, Magnesium pharmacology, Male, Manganese pharmacology, Prostate growth & development, Rats, Rats, Sprague-Dawley, Seminal Vesicles growth & development, Strontium pharmacology, Zinc pharmacology, Aging physiology, Metalloendopeptidases biosynthesis, Prostate enzymology, Seminal Vesicles enzymology
- Abstract
The objective of this study was to characterize proteinase activities expressed during development and maturation of the prostate gland and seminal vesicles of the rat by using gelatin-and casein-containing SDS polyacrylamide gel zymography. The prostatic complexes of 2- and 10-day-old animals and the individual lobes of the prostate (ventral, dorsolateral, and anterior [coagulating gland]) and the seminal vesicles of 15-day-old animals expressed prominent gelatinolytic activities of approximately 64, 71, and 76 kDa. These activities had properties of metalloproteinases; i.e., they were stimulated by Ca2+ and inhibited by EDTA and EGTA. They were greatly diminished by 52 days of age (immediately postpuberty) and were not detected in the dorsal lobe of the adult. Less active gelatinolytic proteinases with molecular masses of approximately 34 and 43 kDa were expressed in the developing prostatic complexes and individual lobes and seminal vesicles, but they were not detected in postpubertal animals. Weak gelatinolytic activities of 82, 85, and 89 kDa were found in the prostatic complexes; these activities were greatly diminished in all prostate lobes with sexual maturation but were expressed in the seminal vesicles at all ages. A large-molecular-mass Ca(2+)-independent proteinase of 130 kDa or greater was first detected in the dorsolateral prostate at 21 days of age. This activity was expressed in both the lateral and dorsal lobes of the adult but was greater in the lateral lobe. Proteinase activities of about 22 and 26 kDa that were not stimulated by Ca2+ were detected in the ventral prostate at 15 days of age by means of both gelatin and casein gels.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
- Full Text
- View/download PDF
32. Heterogeneity of human lymphocyte Fc receptors. II. Relationship to antibody-dependent, cell-mediated cytotoxicity.
- Author
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Gormus BJ, Woodson M, and Kaplan ME
- Subjects
- Cell Aggregation, Cell Membrane immunology, Erythrocytes immunology, Hot Temperature, Humans, Papain, Pronase, Rh-Hr Blood-Group System, Antibody-Dependent Cell Cytotoxicity, Immunoglobulin Fc Fragments immunology, Immunoglobulin G immunology, Lymphocytes immunology
- Published
- 1978
33. Heterogeneity of human lymphocyte Fc receptors. I. Differential susceptibility to proteolysis.
- Author
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Gormus BJ, Woodson M, and Kaplan ME
- Subjects
- Cell Aggregation, Cell Membrane immunology, Erythrocytes immunology, Hot Temperature, Humans, Papain, Pronase, Immunoglobulin Fc Fragments immunology, Immunoglobulin G immunology, Lymphocytes immunology
- Published
- 1978
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