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Search Results: 1 - 10 of 302312 matches for " James E. K. Hildreth "
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Cholesterol Depletion Inactivates XMRV and Leads to Viral Envelope Protein Release from Virions: Evidence for Role of Cholesterol in XMRV Infection
Yuyang Tang, Alvin George, Thyneice Taylor, James E. K. Hildreth
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048013
Abstract: Membrane cholesterol plays an important role in replication of HIV-1 and other retroviruses. Here, we report that the gammaretrovirus XMRV requires cholesterol and lipid rafts for infection and replication. We demonstrate that treatment of XMRV with a low concentration (10 mM) of 2-hydroxypropyl-β-cyclodextrin (2OHpβCD) partially depleted virion-associated cholesterol resulting in complete inactivation of the virus. This effect could not be reversed by adding cholesterol back to treated virions. Further analysis revealed that following cholesterol depletion, virus-associated Env protein was significantly reduced while the virions remained intact and retained core proteins. Increasing concentrations of 2OHpβCD (≥20 mM) resulted in loss of the majority of virion-associated cholesterol, causing disruption of membrane integrity and loss of internal Gag proteins and viral RNA. Depletion of cholesterol from XMRV-infected cells significantly reduced virus release, suggesting that cholesterol and intact lipid rafts are required for the budding process of XMRV. These results suggest that unlike glycoproteins of other retroviruses, the association of XMRV glycoprotein with virions is highly dependent on cholesterol and lipid rafts.
Infection of Female Primary Lower Genital Tract Epithelial Cells after Natural Pseudotyping of HIV-1: Possible Implications for Sexual Transmission of HIV-1
Yuyang Tang, Alvin George, Franklin Nouvet, Stephanie Sweet, Nkiruka Emeagwali, Harry E. Taylor, Glenn Simmons, James E. K. Hildreth
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101367
Abstract: The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call “natural pseudotyping,” expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus.
Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress transcription of unintegrated HIV-1 DNA
Emeagwali Nkiruka,Hildreth James EK
Virology Journal , 2012, DOI: 10.1186/1743-422x-9-277
Abstract: Background Unintegrated HIV-1 DNA serves as transcriptionally active templates in HIV-infected cells. Several host factors including NF-κβ enhance HIV-1 transcription. HIV-1 induced NF-κβ activation can be suppressed by viral protein U (Vpu). Interestingly HIV-1 Vpu shares amino acid homology with cellular Twik-related Acid Sensitive K+ (TASK) channel 1 and the proteins physically interact in cultured cells and AIDS lymphoid tissue. Furthermore, the first transmembrane domain of TASK-1 is functionally interchangeable with Vpu and like Vpu enhances HIV-1 release. Results Here we further characterize the role of TASK channels and Vpu in HIV-1 replication. We demonstrate that both TASK channels and Vpu can preferentially inhibit transcription of unintegrated HIV-1 DNA. Interestingly, TASK-1 ion channel function is not required and suppression of HIV-1 transcription by TASK-1 and Vpu was reversed by overexpression of RelA (NF-κβ p65). Conclusion TASK proteins and Vpu suppress transcription of unintegrated HIV-1 DNA through an NF-κβ-dependent mechanism. Taken together these findings support a possible physiological role for HIV-1 Vpu and TASK proteins as modulators of transcription of unintegrated HIV-1 DNA genomes.
Rice Hull Mulch Affects Germination of Bittercress and Creeping Woodsorrel in Container Plant Culture  [PDF]
James E. Altland, Jennifer K. Boldt, Charles C. Krause
American Journal of Plant Sciences (AJPS) , 2016, DOI: 10.4236/ajps.2016.716207
Abstract: Mulches are commonly used to control weeds in container nursery crops, especially in sites where preemergence herbicides are either not labeled or potentially phytotoxic to the crop. Parboiled rice hulls have been shown to provide effective weed control when applied 1.25 to 2.5 cm deep over the container substrate surface. The objective of this research was to determine if weed seed placement, above or below the mulch layer, affects flexuous bittercress or creeping woodsorrel establishment. Seeds of both species were placed either above or below rice hull mulch layers 0, 0.6, 1.3, or 2.5 cm deep in nursery containers with a 80 pine bark: 20 sphagnum peat moss substrate. Establishment of both weeds decreased with increasing mulch depth. Establishment of both species was generally greater from beneath the mulch compared to when seed were applied above the mulch. Light penetration through varying depths of rice hulls was determined with a spectroradiometer. Photosynthetically active radiation (PAR) decreased exponentially with increasing rice hull depth, and was less than 1 μmol·m-2·s-1 beneath depths greater than 1 cm. Germination of both species was determined in Petri dishes placed beneath varying densities of shade cloth. Flexuous bittercress germination responded quadratically to decreasing light level, but still germinated (13%) in complete darkness after 3 weeks. Creeping woodsorrel germination was not affected by light level and was high (92%) after 3 weeks. The role of light exclusion by rice hulls as a mechanism for controlling buried weed seed is discussed. Water retention immediately after irrigation, and for 24 hr following irrigation, was determined for a 2.5 cm layer of rice hulls, sphagnum peat moss, and pine bark. Rice hulls retained less water, and dried more quickly than peat moss or pine bark. The volumetric water content of the rice hull layer is less than 0.20 cm·cm-1 and what has been shown necessary for plant growth. Lack of water availability in the rice hull layer is discussed as the primary mechanism of control of weed seed above the mulch layer.
Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat
Cara M Hildreth, Ann K Goodchild
BMC Neuroscience , 2010, DOI: 10.1186/1471-2202-11-128
Abstract: Microinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN.We conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.Cardiac vagal preganglionic neurons (CVPN) are found predominantly in the nucleus ambiguus (NA) as well as dorsal motor nucleus of the vagus (DMNV) and in the intermediate zone (IZ) between these two nuclei [1-3]. Activation of CVPN has negative chronotropic, dromotropic and ionotropic effects on the heart [4-6] and the activity of these neurons is increased in response to baroreceptor stimulation [7-9] and inhibited during inspiration [10,11].Surprisingly little is known about the functional significance of inputs to CVPN mediated by either ionotropic or g-protein coupled receptors (GPCR). CVPN receive substantial inputs from ionotropic receptors. Microinjection of the GABAA receptor antagonist bicuculline into the NA evokes a profound decrease in HR [12] demonstrating that there is a large GABAergic input to CVPN that plays a role in setting the tonic level of heart rate (HR). GABAergic inputs
Polarimeters and Energy Spectrometers for the ILC Beam Delivery System
S. Boogert,A. F. Hartin,M. Hildreth,D. K?fer,J. List,T. Maruyama,K. M?nig,K. C. Moffeit,G. Moortgat-Pick,S. Riemann,H. J. Schreiber,P. Schüler,E. Torrence,M. Woods
Physics , 2009, DOI: 10.1088/1748-0221/4/10/P10015
Abstract: Any future high energy e+e- linear collider aims at precision measurements of Standard Model quantities as well as of new, not yet discovered phenomena. In order to pursue this physics programme, excellent detectors at the interaction region have to be complemented by beam diagnostics of unprecedented precision. This article gives an overview of current plans and issues for polarimeters and energy spectrometers at the International Linear Collider, which have been designed to fulfill the precision goals at a large range of beam energies from 45.6 GeV at the Z pole up to 250 GeV or, as an upgrade, up to 500 GeV.
Loss of Niemann Pick type C proteins 1 and 2 greatly enhances HIV infectivity and is associated with accumulation of HIV Gag and cholesterol in late endosomes/lysosomes
Ebony M Coleman, Tiffany N Walker, James EK Hildreth
Virology Journal , 2012, DOI: 10.1186/1743-422x-9-31
Abstract: We used a unique NPC2-deficient cell line (NPCD55) that exhibited Gag accumulation as well as decreased NPC1 expression after HIV infection. Virus release efficiency from NPCD55 cells was similar to that from control cells. However, we observed a 3 to 4-fold enhancement in the infectivity of virus released from these cells. Fluorescence microscopy revealed accumulation and co-localization of Gag proteins with cholesterol in late endosomal/lysosomal (LE/L) compartments of these cells. Virion-associated cholesterol was 4-fold higher in virions produced in NPCD55 cells relative to virus produced in control cells. Treatment of infected NPCD55 cells with the cholesterol efflux-inducing drug TO-9013171 reduced virus infectivity to control levels.These results suggest cholesterol trafficking and localization can profoundly affect HIV-1 infectivity by modulating the cholesterol content of the virions.Cellular cholesterol plays a critical role in various stages of the HIV-1 replication cycle. HIV-1 fusion, entry, assembly, and budding occur at cholesterol-enriched microdomains called lipid rafts [1-4]. The HIV-1 accessory protein, Nef, has been shown to induce many genes involved in cholesterol biosynthesis and homeostasis [5,6]. Depletion of virion-associated cholesterol by beta-cyclodextrin compromises viral structural integrity and significantly decreases both the quantity and infectivity of virions released from infected cells [7,8]. Treatment of HIV particles with cholesterol-sequestering compounds inhibits virus entry into host cells [9,10].Previous studies have shown that Nef inhibits the activity of ATP-binding cassette transporter A1 (ABCA1) in HIV-infected macrophages. The inhibition of ABCA1 leads to suppression of cholesterol efflux and an accumulation of intracellular cholesterol [11]. In turn, this effect increases the cholesterol content of the virions. The proteins implicated in Niemann-Pick Type C (NPC) disease, NPC1 and NPC2, are responsible for the egress
Treatment with Intensity-Modulated Radiation Therapy (IMRT) and Chemotherapy in Advanced Inoperable Non-Small Cell Lung Cancer (NSCLC): Toxicity, Survival and Patterns of Failure in Relation to Treatment with High and Low Radiation Dose  [PDF]
James K. Russo, Daniel Grass, Kent E. Armeson, John Stahl, Tarek Dufan, John Reynolds, Aaron Luebke, Anand K. Sharma
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.611102
Abstract: Purpose: To investigate the toxicity, survival and patterns of failure in patients with advanced lung cancer treated with intensity modulated radiation therapy (IMRT) and chemotherapy. Methods and Materials: Retrospective chart review of 68 total patients: 46 academic and 22 community center. Endpoints: Grade ≥ 3 pneumonitis, Grade ≥ 2 esophagitis, local, regional and distant failure, progression-free survival (PFS) and overall survival (OS). Results: For the academic center patients, median follow-up was 19.2 months. Esophagitis: 0% Grade 3, 35% Grade 2, no significant difference between dose bins: <70 Gy vs. 70 Gy, 25% vs. 45% (p = 0.22), <66 Gy vs. 66 - 70 Gy, 28% vs. 39% (p = 0.53). Lung dose metrics and PTV size were not associated with Grade ≥ 3 pneumonitis. Esophageal V35, V50, and mean dose but not PTV size was associated with Grade 2 esophagitis. 1 year local, regional and distant failure = 6.5%, 6.5%, and 30.4%. No endpoint differences were seen between dose bins, though patients with smaller PTVs treated with 70 Gy did demonstrate improved OS (ns) when compared to those treated with <70 Gy. Community Center: Median follow-up 6.2 months with 15% Grade 2 esophagitis, no Grade 3 esophagitis. Two patients (9%) experienced Grade ≥ 3 pneumonitis. Conclusions: IMRT chemoradiation was well tolerated in a population with advanced NSCLC both in the academic and community settings. Severe pneumonitis rates were low and comparable to other series using IMRT and chemotherapy. Esophagitis was mild and associated with V35, V50 and mean dose. No significant benefit was seen for higher doses regarding survival, local, regional or distant control despite that higher dose bins had smaller tumors. Though not statistically significant, we did find a trend toward worse OS for <70 Gy when the PTV was less than the median PTV.
The Puelche Volcanic Field: extensive Pleistocene rhyolite lava flows in the Andes of central Chile
Wes Hildreth,Judy Fierstein,Estanislao Godoy,Robert E. Drake
Revista geológica de Chile , 1999,
Abstract:
Results from the K2K Long--Baseline Neutrino Oscillation Experiment
James E. Hill,for the K2K Collaboration
Physics , 2001,
Abstract: The K2K Long--Baseline neutrino oscillation experiment has been aquiring data since mid-1999 and has analysed those up to March of 2001. Forty-four fully contained events are observedin the fiducial volume of the far detector where $64^{+6.1}_{-6.6}$ are expected based partly on measurements near the beam production point. There is virtually no background for the contained event search. The methods established in this experiment are crucial for operation of future similar experiments to probe the nature of mixing in the neutral lepton sector, a necessary step in understanding the nature of family structure and of mass itself. A brief history and a few notes about the future and direction of the field precede the description of the experiment and its results.
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