oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2020 ( 9 )

2019 ( 692 )

2018 ( 831 )

2017 ( 761 )

Custom range...

Search Results: 1 - 10 of 467622 matches for " Scott A. Tibbetts "
All listed articles are free for downloading (OA Articles)
Page 1 /467622
Display every page Item
Effective control of chronic gamma-herpesvirus infection by unconventional MHC Class Ia-independent CD8 T cells.
Braaten Douglas C,McClellan James Scott,Messaoudi Ilhem,Tibbetts Scott A
PLOS Pathogens , 2006,
Abstract: Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia-dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (K(b-/-)xD(b-/-) mice) effectively control chronic gamma-herpesvirus 68 (gammaHV68) infection via a robust expansion of beta2-microglobulin (beta2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8alphabeta and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRalphabeta with a significant Vbeta4, Vbeta3, and Vbeta10 bias, and (4) the key effector cytokine interferon-gamma (IFNgamma). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that beta2-m-dependent, but Class Ia-independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for beta2-n-dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia-restricted T cells.
Unbiased Mutagenesis of MHV68 LANA Reveals a DNA-Binding Domain Required for LANA Function In Vitro and In Vivo
Clinton R. Paden,J. Craig Forrest,Scott A. Tibbetts,Samuel H. Speck
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002906
Abstract: The Latency-Associated Nuclear Antigen (LANA), encoded by ORF73, is a conserved gene among the γ2-herpesviruses (rhadinoviruses). The Kaposi's Sarcoma-Associated Herpesvirus (KSHV) LANA is consistently expressed in KSHV-associated malignancies. In the case of the rodent γ2-herpesvirus, murine gammaherpesvirus 68 (MHV68), the LANA homolog (mLANA) is required for efficient virus replication, reactivation from latency and immortalization of murine fetal liver-derived B cells. To gain insights into mLANA function(s), knowing that KSHV LANA binds DNA and can modulate transcription of a variety of promoters, we sought out and identified a mLANA-responsive promoter which maps to the terminal repeat (TR) of MHV68. Notably, mLANA strongly repressed activity from this promoter. We extended these analyses to demonstrate direct, sequence-specific binding of recombinant mLANA to TR DNA by DNase I footprinting. To assess whether the DNA-binding and/or transcription modulating function is important in the known mLANA phenotypes, we generated an unbiased library of mLANA point mutants using error-prone PCR, and screened a large panel of mutants for repression of the mLANA-responsive promoter to identify loss of function mutants. Notably, among the mutant mLANA proteins recovered, many of the mutations are in a predicted EBNA-1-like DNA-binding domain. Consistent with this prediction, those tested displayed loss of DNA binding activity. We engineered six of these mLANA mutants into the MHV68 genome and tested the resulting mutant viruses for: (i) replication fitness; (ii) efficiency of latency establishment; and (iii) reactivation from latency. Interestingly, each of these mLANA-mutant viruses exhibited phenotypes similar to the mLANA-null mutant virus, indicating that DNA-binding is critical for mLANA function.
Murine Gamma-Herpesvirus 68 Hijacks MAVS and IKKβ to Initiate Lytic Replication
Xiaonan Dong,Hao Feng,Qinmiao Sun,Haiyan Li,Ting-Ting Wu,Ren Sun,Scott A. Tibbetts,Zhijian J. Chen,Pinghui Feng
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1001001
Abstract: Upon viral infection, the mitochondrial antiviral signaling (MAVS)-IKKβ pathway is activated to restrict viral replication. Manipulation of immune signaling events by pathogens has been an outstanding theme of host-pathogen interaction. Here we report that the loss of MAVS or IKKβ impaired the lytic replication of gamma-herpesvirus 68 (γHV68), a model herpesvirus for human Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. γHV68 infection activated IKKβ in a MAVS-dependent manner; however, IKKβ phosphorylated and promoted the transcriptional activation of the γHV68 replication and transcription activator (RTA). Mutational analyses identified IKKβ phosphorylation sites, through which RTA-mediated transcription was increased by IKKβ, within the transactivation domain of RTA. Moreover, the lytic replication of recombinant γHV68 carrying mutations within the IKKβ phosphorylation sites was greatly impaired. These findings support the conclusion that γHV68 hijacks the antiviral MAVS-IKKβ pathway to promote viral transcription and lytic infection, representing an example whereby viral replication is coupled to host immune activation.
Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells
Douglas C Braaten equal contributor,James Scott McClellan equal contributor,Ilhem Messaoudi equal contributor,Scott A Tibbetts,Kelly B McClellan,Janko Nikolich-Zugich equal contributor,Herbert W Virgin IV equal contributor
PLOS Pathogens , 2006, DOI: 10.1371/journal.ppat.0020037
Abstract: Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (Kb?/?xDb?/? mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β2-microglobulin (β2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β2-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β2-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells.
A Gammaherpesvirus Bcl-2 Ortholog Blocks B Cell Receptor-Mediated Apoptosis and Promotes the Survival of Developing B Cells In Vivo
Carrie B. Coleman,Jennifer E. McGraw,Emily R. Feldman,Alexa N. Roth,Lisa R. Keyes,Katrina R. Grau,Stephanie L. Cochran,Thomas J. Waldschmidt,Chengyu Liang,J. Craig Forrest,Scott A. Tibbetts
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1003916
Abstract: Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) establish lifelong latency in their hosts and are associated with the development of several types of malignancies, including a subset of B cell lymphomas. These viruses are thought to co-opt the process of B cell differentiation to latently infect a fraction of circulating memory B cells, resulting in the establishment of a stable latency setpoint. However, little is known about how this infected memory B cell compartment is maintained throughout the life of the host. We have previously demonstrated that immature and transitional B cells are long-term latency reservoirs for murine gammaherpesvirus 68 (MHV68), suggesting that infection of developing B cells contributes to the maintenance of lifelong latency. During hematopoiesis, immature and transitional B cells are subject to B cell receptor (BCR)-mediated negative selection, which results in the clonal deletion of autoreactive B cells. Interestingly, numerous gammaherpesviruses encode homologs of the anti-apoptotic protein Bcl-2, suggesting that virus inhibition of apoptosis could subvert clonal deletion. To test this, we quantified latency establishment in mice inoculated with MHV68 vBcl-2 mutants. vBcl-2 mutant viruses displayed a marked decrease in the frequency of immature and transitional B cells harboring viral genome, but this attenuation could be rescued by increased host Bcl-2 expression. Conversely, vBcl-2 mutant virus latency in early B cells and mature B cells, which are not targets of negative selection, was remarkably similar to wild-type virus. Finally, in vivo depletion of developing B cells during chronic infection resulted in decreased mature B cell latency, demonstrating a key role for developing B cells in the maintenance of lifelong latency. Collectively, these findings support a model in which gammaherpesvirus latency in circulating mature B cells is sustained in part through the recurrent infection and vBcl-2-mediated survival of developing B cells.
Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants
David Metzgar,Christopher A. Myers,Kevin L. Russell,Dennis Faix,Patrick J. Blair,Jason Brown,Scott Vo,David E. Swayne,Colleen Thomas,David A. Stenger,Baochuan Lin,Anthony P. Malanoski,Zheng Wang,Kate M. Blaney,Nina C. Long,Joel M. Schnur,Magdi D. Saad,Lisa A. Borsuk,Agnieszka M. Lichanska,Matthew C. Lorence,Brian Weslowski,Klaus O. Schafer,Clark Tibbetts
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008995
Abstract: For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.
Biomass and Abundance of Herbivorous Fishes on Coral Reefs off Andavadoaka, Western Madagascar
IV Vincent, CM Hincksman, IR Tibbetts, A Harris
Western Indian Ocean Journal of Marine Science , 2011,
Abstract: The biomass and abundance of four herbivorous fish families were surveyed in the region of Andavadoaka, south-west Madagascar, investigating the effects of fishing intensity, reef geomorphology and benthic cover. Distance from the village was used as a proxy for fishing effort, with sites closest to the village assumed to have the highest fishing intensity. Both overall herbivore biomass and abundance increased with distance from shore (p=0.002, p<0.001), as well as with increased hard coral cover (p<0.001, p<0.001). Acanthurid biomass (p<0.001) and abundance (p<0.001) increased significantly with distance from the village, as did the abundance of Pomacentridae (p=0.001). Conversely, siganids decreased in biomass with increased distance from the village (p=0.019). Associations between herbivorous fish families and benthos were manifested in a significant (p<0.001) increase in acanthurid and pomacentrid biomass with increased hard coral cover. Sites with increased turf algae displayed lower scarid biomass (p=0.002) and abundance (p=0.032), while siganid abundance increased (p=0.002) as turf algae increased. Reef type has previously been suggested to be an important factor influencing fish biomass, however the results of this study suggest that this has little effect on herbivore biomass in the region. Benthic cover and fishing intensity appear to influence the biomass of herbivorous fish communities more on the reefs of Andavadoaka, highlighting the importance of Marine Protected Areas to protect both corals and fish.
Geographic Variation in the Status Signals of Polistes dominulus Paper Wasps
Elizabeth A. Tibbetts,Oksana Skaldina,Vera Zhao,Amy L. Toth,Maksim Skaldin,Laura Beani,James Dale
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0028173
Abstract: Understanding intraspecific geographic variation in animal signals poses a challenging evolutionary problem. Studies addressing geographic variation typically focus on signals used in mate-choice, however, geographic variation in intrasexual signals involved in competition is also known to occur. In Polistes dominulus paper wasps, females have black facial spots that signal dominance: individuals wasps with more complex ‘broken’ facial patterns are better fighters and are avoided by rivals. Recent work suggests there is dramatic geographic variation in these visual signals of quality, though this variation has not been explicitly described or quantified. Here, we analyze variation in P. dominulus signals across six populations and explore how environmental conditions may account for this variation. Overall, we found substantial variation in facial pattern brokenness across populations and castes. Workers have less broken facial patterns than gynes and queens, which have similar facial patterns. Strepsipteran parasitism, body size and temperature are all correlated with the facial pattern variation, suggesting that developmental plasticity likely plays a key role in this variation. First, the extent of parasitism varies across populations and parasitized individuals have lower facial pattern brokenness than unparasitized individuals. Second, there is substantial variation in body size across populations and a weak but significant relationship between facial pattern brokenness and body size. Wasps from populations with smaller body size (e.g. Italy) tend to have less broken facial patterns than wasps from populations with larger body size (e.g. New York, USA). Third, there is an apparent association between facial patterns and climate, with wasp from cooler locations tending to have higher facial pattern brokenness than wasps from warmer locations. Additional experimental work testing the causes and consequences of facial pattern variation will be important, as geographic variation in signals has important consequences for the evolution of communication systems and social behavior.
Identification of Genetic Modifiers of TDP-43 Neurotoxicity in Drosophila
Lihong Zhan, Keith A. Hanson, Sang Hwa Kim, Apeksha Tare, Randal S. Tibbetts
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057214
Abstract: Cytosolic aggregation of the nuclear RNA-binding protein TDP-43 is a histopathologic signature of degenerating neurons in amyotrophic lateral sclerosis (ALS), and mutations in the TARDBP gene encoding TDP-43 cause dominantly inherited forms of this condition. To understand the relationship between TDP-43 misregulation and neurotoxicity, we and others have used Drosophila as a model system, in which overexpression of either wild-type TDP-43 or its ALS-associated mutants in neurons is sufficient to induce neurotoxicity, paralysis, and early death. Using microarrays, we have examined gene expression patterns that accompany TDP-43-induced neurotoxicity in the fly system. Constitutive expression of TDP-43 in the Drosophila compound eye elicited widespread gene expression changes, with strong upregulation of cell cycle regulatory genes and genes functioning in the Notch intercellular communication pathway. Inducible expression of TDP-43 specifically in neurons elicited significant expression differences in a more restricted set of genes. Genes that were upregulated in both paradigms included SpindleB and the Notch target Hey, which appeared to be a direct TDP-43 target. Mutations that diminished activity of Notch or disrupted the function of downstream Notch target genes extended the lifespan of TDP-43 transgenic flies, suggesting that Notch activation was deleterious in this model. Finally, we showed that mutation of the nucleoporin Nup50 increased the lifespan of TDP-43 transgenic flies, suggesting that nuclear events contribute to TDP-43-dependent neurotoxicity. The combined findings identified pathways whose deregulation might contribute to TDP-43-induced neurotoxicity in Drosophila.
Undoped Electron-Hole Bilayers in a GaAs/AlGaAs Double Quantum Well
J. A. Seamons,D. R. Tibbetts,J. L. Reno,M. P. Lilly
Physics , 2006, DOI: 10.1063/1.2437664
Abstract: We present the fabrication details of completely undoped electron-hole bilayer devices in a GaAs/AlGaAs double quantum well heterostructure with a 30 nm barrier. These devices have independently tunable densities of the two-dimensional electron gas and two-dimensional hole gas. We report four-terminal transport measurements of the independently contacted electron and hole layers with balanced densities from $1.2 \times 10^{11}$cm$^{-2}$ down to $4 \times 10^{10}$ cm$^{-2}$ at $T = 300 mK$. The mobilities can exceed $1 \times 10^{6}$ cm$^{2}$ V$^{-1}$ s$^{-1}$ for electrons and $4 \times 10^{5}$ cm$^{2}$ V$^{-1}$ s$^{-1}$ for holes.
Page 1 /467622
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.