Interaction Of gD Research Articles

Ciprofloxacin Metal Complexes–Silica Nanoparticles: Characterization, Spectroscopic Study, DNA Interaction and Biological Activity

Ciprofloxacin (CIPH) was classified as one of the most effective quinolone antibiotics, which is commonly used to cure a wide range of infections resulting from Gram-negative and Gram-positive microorganisms. The complexes which formed due to the interaction of Ni(II), Zn(II), Cu(II), Gd(III) and Sm(III) with ciprofloxacin were characterized by CHN% analysis, conductivity, FTIR, electronic spectra, fluorescence measurements, and magnetic susceptibility, besides studying the complex–DNA interaction. Meanwhile, the molar conductance values (0.001 mol·L−1 in DMSO) revealed the electrolytic behavior of the complexes and could be designated with the A−B+ formula. In addition, the geometry of the compounds was confirmed from the electronic transitions as well as the μeff values as octahedral for all complexes. The postulated formula could be generally assigned as [M(CIP)a(CIPH)b(H2O)c](NO3)(H2O)n(C2H5OH)m. Moreover, the interaction between metal complexes and DNA revealed that the Cu complex had the highest binding constant. Nanotechnology was applied to synthesized compounds using silica nanoparticles (SiNPs), which were prepared using a sol–gel process. The silica nanoparticles were chemically functionalized for binding the ligand and its metal complexes; this enables the as-prepared compounds to enhance their features as a drug delivery platform. Meanwhile, the antimicrobial activity was tested for the free complexes and SiNPs composites. Collectively, Sm complex gave the largest zone of inhibition, while the Cu(II)–SiNPs composite showed the strongest potential to reduce the bacterial activity. Furthermore, the fluorescence data of CIPH, ligand–metal mixture and the effect of silica nanoparticles on them were studied.

Anti-HSV activity of nectin-1-derived peptides targeting HSV gD: an in-silico and in-vitro approach

Herpes simplex virus (HSV) infections affect a wide range of the global population. The emergence of resistance to the existing anti-HSV therapy highlights the necessity for an innovative strategy. The interaction of HSV gD with its main host receptor nectin-1 is a potential target for new antiviral drugs. The aim of this study was to develop a peptide derived from nectin-1 targeting HSV gD using the in-silico method and evaluate them for anti-HSV activity. Residues 59-133 of the Nectin-1 V-domain constitute the interaction interface with HSV gD. Bioinformatic tools viz., PEP-FOLD3, ClusPro 2.0, HawkDock and Desmond were used to model the peptide and confirm its binding specificity with HSV gD protein. The peptides with potential interactions were custom synthesized and anti-HSV activity was evaluated in vitro against HSV-1 and HSV-2 by CPE inhibition assay. Five peptide sequences were identified as exhibiting good interaction with HSV-gD proteins. Among them, peptide N1 (residues 76–90) offered maximum protection against HSV-1 (66.57%) and HSV-2 (71.12%) infections. Modification of the identified peptide through peptidomimetic approaches may further enhance the activity and stability of the identified peptide. Communicated by Ramaswamy H. Sarma

Enhanced Alkaline Hydrogen Evolution on Gd1.0/Ndx (x = 0.5, 1.0, 3.0, and 6.0%)-Doped TiO2 Bimetallic Electrocatalysts

The work reports a facile synthesis of high thermally stable nanocrystalline anatase TiO2 nanoparticles (NPs) doped with different atomic concentrations (0.5, 1.0, 3.0, and 6.0%) of Gd3+ and Nd3+ ions by a template-free and one-step solvothermal process, using titanium(IV) butoxide as a titanium precursor and dimethyl sulfoxide (DMSO) as a solvent. The structure and morphology of the Gd3+, Nd3+, and 0.5%Gd3+-0.5%Nd3+/doped TiO2 NPs have been characterized by using various analytical techniques. The Gd3+/ and Nd3+/TiO2 molar ratios were found to have a pronounced impact on the crystalline structure, size, and morphology of TiO2 NPs. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) studies revealed the proper substitution of Ti4+ by Gd3+ and Nd3+ ions in the TiO2 host lattice. The as-prepared Gdx/TiO2, Ndx/TiO2, and Gd1.0/Ndx/TiO2 bimetallic NPs, x = 0.5, 1.0, 3.0, and 6%, have been investigated as electrocatalysts for hydrogen evolution reaction (HER) in 1.0 M KOH solution using a variety of electrochemical techniques. At any doping percentage, the Gd1.0/Ndx/TiO2 bimetallic NPs showed higher HER catalytic performance than their corresponding counterparts, i.e., Gdx/TiO2 and Ndx/TiO2. Upon increasing the Nd content from 0.5 to 6.0%, the HER catalytic performance of the Gd1.0/Ndx/TiO2 bimetallic NPs was generally enhanced. Among the studied materials, the bimetallic Gd1.0/Nd6.0/TiO2 NPs emerged as the most promising catalyst with an onset potential of −22 mV vs. RHE, a Tafel slope of 109 mV dec−1, and an exchange current density of 0.72 mA cm−2. Such HER electrochemical kinetic parameters are close to those recorded by the commercial Pt/C (onset potential: −15 mV, Tafel slope: 106 mV dec−1, and exchange current density: 0.80 mA cm−2), and also comparable with those measured by the most active electrocatalysts reported in the literature. The synergistic interaction of Gd and Nd is thought to be the major cause of the bimetallic catalyst’s activity.

Cell entry of Bovine herpesvirus-1 through clathrin- and caveolin-mediated endocytosis requires activation of PI3K-Akt-NF-κB and Ras-p38 MAPK pathways as well as the interaction of BoHV-1 gD with cellular receptor nectin-1

Bovine herpesvirus-1 (BoHV-1) can infect all breeds of cattle and cause severe respiratory organs and genital tract diseases. However, the mechanism of BoHV-1 entering the cells remains unclear. In this study, we explored the mechanism of BoHV-1 entering MDBK cells. We found that the entry of BoHV-1 was blocked by NH4Cl and bafilomycin A1, indicating that BoHV-1 entry is dependent on the acidic environment of endosome. Specific inhibitor dynasore and small interfering RNA (siRNA) knockdown of dynamin-2 inhibited BoHV-1 entry, showing that dynamin is required in BoHV-1 entry. The results of specific inhibitor, siRNA knockdown and co-localization indicating clathrin- and caveolin- mediated endocytosis play a role in BoHV-1 entry. BoHV-1 infection was not affected by EIPA which is a specific inhibitor of macropinocytosis. In addition, we found that BoHV-1 triggered PI3K-Akt-NF-κB and Ras-p38 MAPK signaling pathways to induce clathrin-mediated and caveolin-mediated endocytosis at the early stage of BoHV-1 infection. BoHV-1 binding was sufficient to activate the endocytic signaling pathways and promote viral entry. These two signaling pathways were activated by transfection of viral gD protein, and were inhibited by deletion of viral gD protein and the siRNA knockdown of cellular receptor nectin-1. The results of co-localization indicating the entered BoHV-1 is traced to late endosomes via early endosomes. Our results suggested the interaction of viral gD protein and cellular receptor nectin-1 triggered the PI3K-Akt-NF-κB and Ras-p38 MAPK signaling pathways and induced clathrin-mediated and caveolin-mediated endocytosis to promote BoHV-1 entry into MDBK cells at the early stage of BoHV-1 infection.

Gd3+ and Bi3+ co-substituted cubic zirconia; (Zr1-x-y Gd x Bi y O2-δ ): a novel high κ relaxor dielectric and superior oxide-ion conductor.

Solid oxide fuel cells (SOFCs) offer several advantages over lower temperature polymeric membrane fuels cells (PMFCs) due to their multiple fuel flexibility and requirement of low purity hydrogen. In order to decrease the operating temperature of SOFCs and to overcome the high operating cost and materials degradation challenges, the Cubic phase of ZrO2 was stabilized with simultaneous substitution of Bi and Gd and the effect of co-doping on the oxide-ion conductivity of Zr1−x−yBixGdyO2−δ was studied to develop a superior electrolyte separator for SOFCs. Up to 30% Gd and 20% Bi were simultaneously substituted in the cubic ZrO2 lattice (Zr1−x−yGdxBiyO2−δ, x + y ≤ 0.4, x ≤ 0.3 and y ≤ 0.2) by employing a solution combustion method followed by multiple calcinations at 900 °C. Phase purity and composition of the material is confirmed by powder XRD and EDX measurements. The formation of an oxygen vacant Gd/Bi co-doped cubic zirconia lattice was also confirmed by Raman spectroscopy study. With the incorporation of Bi3+ and Gd3+ ions, the cubic Zr1−x−yBixGdyO2−δ phase showed relaxor type high κ dielectric behaviour (ε′ = 9725 at 600 °C at applied frequency 20 kHz for Zr0.6Bi0.2Gd0.2O1.8) with Tm approaching 600 °C. The high polarizability of the Bi3+ ion coupled with synergistic interaction of Bi and Gd in the host ZrO2 lattice seems to create the more labile oxide ion vacancies that enable superior oxide-ion transport resulting in high oxide ion conductivity (σo > 10−2 S cm−1, T > 500 °C for Zr0.6Bi0.2Gd0.2O1.8) at relatively lower temperatures.

Enhanced photoluminescence properties of Gd (x-1) Sr x O: CdO nanocores and their study of optical, structural, and morphological characteristics

Synthesis of Gd doped Srx O: CdO (x = 1.4, 1.6, 1.8) nanostructures (NS) was achieved through the coprecipitation method by using CTAB (cetyl trimethyl ammonium bromide) with the purpose to investigate the effect of Gd doping on the optical, structural, morphological, and photoluminescence properties at room temperature. Mixed phase of tetragonal crystal structure verified via X-ray diffraction technique, no structural variation was observed except lattice distortion. Size of the crystallites (D), morphology studied by SEM (scanning electron microscopy) analysis, nanoparticles (NPs) crystalized roughly flake-like morphology with homogeneous particle distribution centered at ~ 78 nm, ~56 nm, ~65 nm, ~88 nm for pure and Gd (x-1) doped Sr xO: CdO nanostructure, respectively. Fourier transform infrared spectroscopic investigation (FTIR) revealed the presence of Gd–O–Gd, Cd–O, Sr–O, and OH peaks appeared at ~1321 cm −1, ~1550 cm −1, ~1400 cm −1–3300 cm −1 with small variation in vibration modes due to Gd doping. Optical absorptivity observed in the range of 325 nm–359 nm (redshifted) with absorption edges at 346 nm, 364 nm, and 380 nm for Gd (x-1) doped Sr xO: CdO nanostructure, respectively. This redshift on the bandgap was discussed in terms of new band levels below conduction band. The energy gap was calculated using Kubelka-Munk theory and was found to be in the range of 3.22 eV–2.61 eV. X-ray photoelectron spectroscopy (XPS) performed to determine chemical composition and binding energies of Gd 3d 3/2, Sr 3d 3/2, and Cd 3d 3/2, O1s, and C1s observed at 150.8 eV, 141.6 eV, 411.0 eV, 530.4 eV, and 285.6 eV indicating Gd+3 ion replaces Sr+2 in all concentrations. Our results showed that Gd-doped Sr xO: CdO nanoparticles exhibited enhanced photoluminescence (PL) properties in contrast to the pure Gd2O3 with Gd+3 randomly incorporated into crystal structure, probably in tetrahedral sites. The composition of Gd 0.6 doped Sr x O: CdO NS exhibited photoluminescent emission spectra, peaks centered at 433 ± 3 nm, 449 ± 3 nm, and 469 ± 2 nm (λ excitation = 318 nm) and for Gd 0.8 doped Sr x O: CdO nanostructure showed broad emission peak at 412 ± 2 nm to 433 ± 2 nm (λ excitation = 380 nm), which indicates a reduction in defects with an increase in Gd doping. The transitions can be ascertained with shielding of 4f shells of Gd +3 ions by 6s, 5d shells by the interaction of other Gd +3 ions.

Mimicking the graphene oxide structure in solutions by interaction of Fe(III) and Gd(III) with model small-size ligands. The NMR relaxation study

Despite long history and recent progress, the chemical behavior of graphene oxide (GO) is not fully understood. One of the remaining open questions is an extremely high cation exchange capacity, which cannot be explained in the frames of the commonly accepted Lerf-Klinowski structural model. The interaction of GO with metals, termed as sorption, is usually considered as physisorption, or as non-specific electrostatic attraction. Recently, we demonstrated that in fact this interaction has the coordinate-covalent bonding nature. In this work, by the means of the NMR relaxation, we investigated the interaction of Fe(III) and Gd(III) ions with several small molecule size chelators and with linear polymers in order to possibly mimic the GO structure. The experiments were conducted in the broad pH range, and at the different metal/chelator ratios. From the two tested metal ions, Fe(III) has the stronger affinity toward GO due to its higher charge density. GO binds Fe(III) with formation of strong high-relaxivity complexes, which do not undergo hydrolysis even in basic conditions. Numerous model small-size molecules, tested to mimic the GO structure, did not demonstrate the same effect on the relaxation of the Fe(III) and Gd(III) solutions, as does interaction with GO. From the tested linear polymers, only polyacrylic acid (PAA) can bind Fe(III), however, even PAA, consisting from carboxyl groups, cannot prevent Fe(III) from hydrolysis already in neutral solutions. Subsequently, carboxyl groups were excluded from the species in GO structure, responsible for the strong binding of meatal ions. We conclude that there are no preexisting sites or functional group fragments in GO structure, capable to strongly bind transition metal cations. The binding sites are formed from the existing structure upon the reaction with metal cations, to afford formation of the metal/GO coordination compounds. The most probable change in the GO structure is the formation of enolates from tertiary alcohols with rupture of the CC bonds. The newly reported data provide additional experimental evidence for the Dynamic Structural Model of GO and broadens the areas of its applicability.

Exploring optical properties of Gd doped zincblende GaN for novel optoelectronic applications (A DFT+U study)

In current research, we investigate optical properties of Gd doped zincblende GaN using Wien2K code, by employing DFT+U. We consider pure GaN and we dope various Gd concentrations 3.12%, 6.25% and 12.5% into the host GaN lattice while supercell size is kept fixed (1 × 2 × 2) for all cases. We elaborate and present a detailed comparison among optical and electronic properties of pure GaN with various Gd concentrations. Interaction of Gd and N atoms and localization of d and f states of dopant are remarked near Fermi level or maxima of valence band. In comparison to pure GaN, absorption spectra for 3.12% Gd concentration shows redshift but for highest Gd concentration (6.25% 12.5%), a blueshift in absorption spectrum is noted. Absorption is pronounced and enhanced in the UV region. Study of optical spectra for various optical properties suggest that Gd:GaN system is mostly suitable for UV optoelectronics. Results for optical properties have great similarity with the existing literature works. Our unprecedented and first ever reported results on optical properties of Gd:GaN system, direct future path of this material for its potential uses in UV optoelectronic, photonic, LEDs, UV sterilization application, photosensors, thermochromic solar cells and biochemical sensing industries.

High-Temperature Interaction of Liquid Gd with Y2O3

The sessile drop method combined with contact heating procedure was applied for the investigation of high-temperature interaction between liquid Gd and Y2O3 substrate. Real-time behavior of Gd sample in flowing inert gas (Ar) atmosphere upon heating to and at temperature of 1362 °C was recorded using high-speed high-resolution CCD camera. The results evidenced that molten Gd wets Y2O3 substrate (the contact angle θ < 90°) immediately after melting of metal sample observed at T = 1324 °C (Tm = 1312 °C). During the first 3 min of the sessile drop test, the contact angle dropped from θ = 52° to θ = 24° and then stabilized at the final value of θf* = 33°. The solidified Gd/Y2O3 couple was subjected to structural characterization using optical microscopy, scanning electron microscopy coupled with x-ray energy-dispersive spectroscopy. The results evidenced that the wettability in the Gd/Y2O3 system has a reactive nature and the leading mechanism of the interaction between liquid Gd and Y2O3 is the dissolution of the ceramic in the liquid metal responsible for the formation of a deep crater in the substrate under the drop. Therefore, the final contact angle θf*, estimated from the side-view drop image, should be considered as an apparent value, compared to the more reliable value of θf = 70° measured on the cross section of the solidified couple.

Using Antibodies and Mutants To Localize the Presumptive gH/gL Binding Site on Herpes Simplex Virus gD.

HSV virus-cell and cell-cell fusion requires multiple interactions between four essential virion envelope glycoproteins, gD, gB, gH, and gL, and between gD and a cellular receptor, nectin-1 or herpesvirus entry mediator (HVEM). Current models suggest that binding of gD to receptors induces a conformational change that leads to activation of gH/gL and consequent triggering of the prefusion form of gB to promote membrane fusion. Since protein-protein interactions guide each step of fusion, identifying the sites of interaction may lead to the identification of potential therapeutic targets that block this process. We have previously identified two "faces" on gD: one for receptor binding and the other for its presumed interaction with gH/gL. We previously separated the gD monoclonal antibodies (MAbs) into five competition communities. MAbs from two communities (MC2 and MC5) neutralize virus infection and block cell-cell fusion but do not block receptor binding, suggesting that they block binding of gD to gH/gL. Using a combination of classical epitope mapping of gD mutants with fusion and entry assays, we identified two residues (R67 and P54) on the presumed gH/gL interaction face of gD that allowed for fusion and viral entry but were no longer sensitive to inhibition by MC2 or MC5, yet both were blocked by other MAbs. As neutralizing antibodies interfere with essential steps in the fusion pathway, our studies strongly suggest that these key residues block the interaction of gD with gH/gL.IMPORTANCE Virus entry and cell-cell fusion mediated by HSV require gD, gH/gL, gB, and a gD receptor. Neutralizing antibodies directed against any of these proteins bind to residues within key functional sites and interfere with an essential step in the fusion pathway. Thus, the epitopes of these MAbs identify critical, functional sites on their target proteins. Unlike many anti-gD MAbs, which block binding of gD to a cellular receptor, two, MC2 and MC5, block a separate, downstream step in the fusion pathway which is presumed to be the activation of the modulator of fusion, gH/gL. By combining epitope mapping of a panel of gD mutants with fusion and virus entry assays, we have identified residues that are critical in the binding and function of these two MAbs. This new information helps to define the site of the presumptive interaction of gD with gH/gL, of which we have limited knowledge.

Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus.

Herpes simplex virus (HSV) is investigated not only as a human pathogen but also as a promising agent for oncolytic virotherapy. We previously showed that both the initial entry and subsequent lateral spread of HSV can be retargeted to cells expressing tumor-associated antigens by single-chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD-retargeted HSVs to determine whether viral tropism remained dependent on the interaction of gD with the target receptor. Entry and spread profiles of the recombinant viruses indicated that gD retargeting does not abolish the hyperfusogenic activity of syncytial mutations and that these mutations do not eliminate the dependence of HSV entry and spread on a specific gD-receptor interaction. These observations suggest that syncytial mutations may be valuable for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors.

Associating a negatively charged GdDOTA-derivative to the Pittsburgh compound B for targeting Aβ amyloid aggregates.

We have conjugated the tetraazacyclododecane-tetraacetate (DOTA) chelator to Pittsburgh compound B (PiB) forming negatively charged lanthanide complexes, Ln(L4), with targeting capabilities towards aggregated amyloid peptides. The amphiphilic Gd(L4) chelate undergoes micellar aggregation in aqueous solution, with a critical micellar concentration of 0.68 mM, lower than those for the neutral complexes of similar structure. A variable temperature (17)O NMR and NMRD study allowed the assessment of the water exchange rate, k ex (298) = 9.7 × 10(6) s(-1), about the double of GdDOTA, and for the description of the rotational dynamics for both the monomeric and the micellar forms of Gd(L4). With respect to the analogous neutral complexes, the negative charge induces a significant rigidity of the micelles formed, which is reflected by slower and more restricted local motion of the Gd(3+) centers as evidenced by higher relaxivities at 20-60 MHz. Surface Plasmon Resonance results indicate that the charge does not affect significantly the binding strength to Aβ1-40 [K d = 194 ± 11 μM for La(L4)], but it does enhance the affinity constant to human serum albumin [K a = 6530 ± 68 M(-1) for Gd(L4)], as compared to neutral counterparts. Protein-based NMR points to interaction of Gd(L4) with Aβ1-40 in the monomer state as well, in contrast to neutral complexes interacting only with the aggregated form. Circular dichroism spectroscopy monitored time- and temperature-dependent changes of the Aβ1-40 secondary structure, indicating that Gd(L4) stabilizes the random coil relative to the α-helix and β-sheet. TEM images confirm that the Gd(L4) complex reduces the formation of aggregated fibrils.

Interaction of Gd and N incorporation on the band structure and oxygen vacancies of HfO2 gate dielectric films

The interaction of Gd and N incorporation on the band gap, band offset, and oxygen vacancies of HfO2 high-k gate dielectric films has been investigated. The results show that introducing N (9.7% and 17.4%) and Gd into HfO2 does not dramatically reduce the band gap due to the counteracting effect of Gd doping. Most importantly, Gd and N co-doping increases the conduction band offset of HfO2 and leads to a much better band offset symmetry compared to undoped or Gd-monodoped HfO2. Compared with Gd, N plays a more significant role in improving the band-offset symmetry. The oxygen vacancies are greatly suppressed by Gd and N co-doping under the suitable doping amounts.

Facile fabrication of Gd(OH)3 nanorod/RGO composite: Synthesis, characterisation and photocatalytic reduction of Cr(VI)

Abstract Well crystalline, phase pure and stable Gd(OH) 3 nanorod/RGO composite was synthesised by a facile hydrothermal method without using any structural directing agent. Composite formation, structural, morphological, optical and photoelectrochemical characterisation of the nanocomposites were examined by Powder X-ray diffraction pattern (PXRD), Raman spectral analysis, Scanning electron microscopy (SEM), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM), Diffuse reflectance UV–Vis (DRUV–Vis), Photoluminescence spectroscopy (PL) and Photocurrent measurement. The synthesised Gd(OH) 3 nanorod/RGO composite showed 2 and 3-fold higher photo catalytic activity compared to pure 1D-Gd(OH) 3 nanorod and Gd(OH) 3 nanoparticle, respectively for the photoreduction of Cr(VI) ion from water. The high photocatalytic activity of Gd(OH) 3 nanorod/RGO composite has been ascribed to the strong interaction of Gd(OH) 3 nanorod with RGO which leads to easy diffusion and transport of photoexcited electron (e − ) on the layer surface of RGO resulting in the inhibition of electron (e − )–hole (h + ) recombination. The enhanced activity of Gd(OH) 3 nanorod/RGO composite is also well explained in terms of light harvesting property, significant quenching of its luminescence intensity, high photocurrent generation (18 times more than neat Gd(OH) 3 nanorod) and high surface area.

Neutron conversion efficiency and gamma interference with gadolinium

Gadolinium (Gd) neutron capture plays an important role in both Gd neutron capture therapy and neutron detection. Detailed information about the low-energy electron spectrum emitted after Gd neutron capture is essential for accurately determining the dose delivery to the target and healthy tissues, as well as the effectiveness of Gd against other neutron convertors such as boron (B) and lithium (Li). Owing to issues such as charge extraction associated with the low energy of internal conversion electrons (ICEs) and high gamma interaction of Gd, its competitiveness for certain applications remains debatable. We measured the ICE spectrum of Gd, compared the energy deposition rates of neutron capture products from Gd, B, and Li compounds, and discussed issues associated with gamma sensitivity of Gd.

HIV-Associated Disruption of Tight and Adherens Junctions of Oral Epithelial Cells Facilitates HSV-1 Infection and Spread

Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

Influences of different environmental parameters on the sorption of trivalent metal ions on bentonite: batch sorption, fluorescence, EXAFS and EPR studies

The presence of long-lived radionuclides in natural aquatic systems is of great environmental concern in view of their possible migration into biospheres of mankind. Trivalent actinides such as (241/243)Am can contribute a great deal to radioactivity for several thousand years. This migration is significantly influenced by various factors such as pH, complexing ions present in aquatic environments, and the sorption of species involving radionuclides by sediments around water bodies. Clay minerals such as bentonite are known to be highly efficient in radionuclide retention and hence are suitable candidates for backfill materials. This study presents experimental results on the interaction of Eu(iii) and Gd(iii) (chemical analogs of Am(iii) and Cm(iii)) with bentonite clay under varying experimental conditions of contact time, pH, and the presence of complexing anions such as humic acid (HA) and citric acid (cit). The sorption of HA on bentonite decreased with increasing the pH from 2 to 8, which was attributed to electrostatic interactions between HA and the bentonite surfaces. The sorption of Eu(iii) on bentonite colloids showed marginal variation with pH (>95%). However, a decrease in Eu(iii) sorption was observed in the presence of HA beyond pH 5 due to the increased aqueous complexation of Eu(iii) with deprotonated HA in the aqueous phase. The complexation of Eu(iii) with citrate ions was studied using Time Resolved Laser induced Fluorescence Spectroscopy (TRLFS) to explain the sorption data. Extended X-ray absorption fine structure (EXAFS) and electron paramagnetic resonance (EPR) investigations were carried out to understand the local chemical environment surrounding Eu(iii) and Gd(iii) (EPR probe) sorbed on bentonite under different experimental conditions. Surface complexation modelling shows the predominant formation of ≡XOEu(+2) (silanol) up to pH < 7, and beyond which ≡YOEu(OH)(+) (aluminol) is responsible for the quantitative sorption of Eu(iii) onto bentonite in the studied pH range.

Gd3+ complexes conjugated to Pittsburgh compound B: potential MRI markers of β-amyloid plaques

In an effort towards the visualization of β-amyloid (Aβ) plaques by T1-weighted magnetic resonance imaging for detection of Alzheimer's disease, we report the synthesis and characterization of stable, noncharged Gd(3+) complexes of three different 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide derivatives conjugated to Pittsburgh compound B, a well-established marker of Aβ plaques. The ligands L1, L2, and L3 differ in the nature and size of the spacer linking the macrocyclic chelator and the Pittsburgh compound B targeting moiety, which affects their lipophilicity, the octanol-water partition coefficients of the complexes ranging from -0.15 to 0.32. Given their amphiphilic behavior, the complexes form micelles in aqueous solution (critical micellar concentration 1.00-1.49 mM). The parameters determining the relaxivity, including the water exchange rate and the rotational correlation times, were assessed for the monomeric and the micellar form by a combined (17)O NMR and (1)H nuclear magnetic relaxation dispersion (NMRD) study. They are largely influenced by the aggregation state and the hydrophobic character of the linkers. The analysis of the rotational dynamics for the aggregated state in terms of local and global motions using the Lipari-Szabo approach indicates highly flexible, large aggregates. On binding of the complexes to human serum albumin or to the amyloid peptide Aβ1-40 in solution, they undergo a fourfold and a twofold relaxivity increase, respectively (40 MHz). Proton relaxation enhancement studies confirmed moderate interaction of Gd(L1) and Gd(L3) with human serum albumin, with KA values ranging between 250 and 910 M(-1).

A Herpes Simplex Virus 2 Glycoprotein D Mutant Generated by Bacterial Artificial Chromosome Mutagenesis Is Severely Impaired for Infecting Neuronal Cells and Infects Only Vero Cells Expressing Exogenous HVEM

We constructed a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) clone, bHSV2-BAC38, which contains full-length HSV-2 inserted into a BAC vector. Unlike previously reported HSV-2 BAC clones, the virus genome inserted into this BAC clone has no known gene disruptions. Virus derived from the BAC clone had a wild-type phenotype for growth in vitro and for acute infection, latency, and reactivation in mice. HVEM, expressed on epithelial cells and lymphocytes, and nectin-1, expressed on neurons and epithelial cells, are the two principal receptors used by HSV to enter cells. We used the HSV-2 BAC clone to construct an HSV-2 glycoprotein D mutant (HSV2-gD27) with point mutations in amino acids 215, 222, and 223, which are critical for the interaction of gD with nectin-1. HSV2-gD27 infected cells expressing HVEM, including a human epithelial cell line. However, the virus lost the ability to infect cells expressing only nectin-1, including neuronal cell lines, and did not infect ganglia in mice. Surprisingly, we found that HSV2-gD27 could not infect Vero cells unless we transduced the cells with a retrovirus expressing HVEM. High-level expression of HVEM in Vero cells also resulted in increased syncytia and enhanced cell-to-cell spread in cells infected with wild-type HSV-2. The inability of the HSV2-gD27 mutant to infect neuronal cells in vitro or sensory ganglia in mice after intramuscular inoculation suggests that this HSV-2 mutant might be an attractive candidate for a live attenuated HSV-2 vaccine.

Purified Herpes Simplex Type 1 Glycoprotein D (gD) Genetically Fused with the Type 16 Human Papillomavirus E7 Oncoprotein Enhances Antigen-Specific CD8+ T Cell Responses and Confers Protective Antitumor Immunity

Type 1 herpes virus (HSV-1) glycoprotein D (gD) enhances antigen-specific immune responses, particularly CD8(+) T cell responses, in mice immunized with DNA vaccines encoding hybrid proteins genetically fused with the target antigen at a site near the C-terminal end. These effects are attributed to the interaction of gD with the herpes virus entry mediator (HVEM) and the concomitant blockade of a coinhibitory mechanism mediated by the B- and T-lymphocyte attenuator (BTLA). However, questions concerning the requirement for endogenous synthesis of the antigen or the adjuvant/antigen fusion itself have not been addressed so far. In the present study, we investigated these points using purified recombinant gDs, genetically fused or not with type 16 papilloma virus (HPV-16) E7 oncoprotein. Soluble recombinant gDs, but not denatured forms, retained the ability to bind surface-exposed cellular receptors of HVEM-expressing U937 cells. In addition, in vivo administration of the recombinant proteins, particularly gD genetically fused with E7 (gDE7), promoted the activation of dendritic cells (DC) and antigen-specific cytotoxic CD8(+) T cells. More relevantly, mice immunized with the gDE7 protein developed complete preventive and partial therapeutic antitumor protection, as measured in mice following the implantation of TC-1 cells expressing HPV-16 oncoproteins. Collectively, these results demonstrate that the T cell adjuvant effects of the HSV-1 gD protein did not require endogenous synthesis and could be demonstrated in mice immunized with purified recombinant proteins.