Gauge copies in the Landau-DeWitt gauge: a background invariant restriction

The Landau background gauge, also known as the Landau-DeWitt gauge, has found renewed interest during the past decade given its usefulness in accessing the confinement-deconfinement transition via the vacuum expectation value of the Polyakov loop, describable via an appropriate background. In this Letter, we revisit this gauge from the viewpoint of it displaying gauge (Gribov) copies. We generalize the Gribov-Zwanziger effective action in a BRST and background invariant way; this action leads to a restriction on the allowed gauge fluctuations, thereby eliminating the infinitesimal background gauge copies. The explicit background invariance of our action is in contrast with earlier attempts to write down and use an effective Gribov-Zwanziger action. It allows to address certain subtleties arising in these earlier works, such as a spontaneous and thus spurious Lorentz symmetry breaking, something which is now averted.Comment: 14 pages. v2: version to appear in Phys.Lett.B, with minor modifications and extra reference

1,3-<i>syn</i>-Diaxial Repulsion of Typical Protecting Groups Used in Carbohydrate Chemistry in 3‑<i>O</i>‑Substituted Derivatives of Isopropyl d‑Idopyranosides

The strength of 1,3-<i>syn</i>-diaxial repulsion was evaluated for main types of protecting groups (alkyl, silyl, and acyl) usually used in carbohydrate chemistry. As molecular probes for this study, derivatives of isopropyl 2-<i>O</i>-benzyl-4,6-<i>O</i>-benzylidene-α-d-idopyranoside bearing allyl, acetyl, and <i>tert</i>-butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from <i>p</i>-methoxyphenyl d-galactopyranoside. The equilibrium between ^<i>O</i><i>S</i>₂ and ⁴<i>C</i>₁ conformations in these compounds was investigated using ³<i>J</i>_H,H and ³<i>J</i>_C,H coupling constants that were determined from 1D ¹H NMR and 2D <i>J</i>-resolved HMBC spectra in various solvents. The analysis of the corresponding coupling constants calculated using DFT/B3LYP/pcJ-1 approximation applied to conformations optimized at DFT/B3LYP/6-311++G** level supported the investigation. Proportions of conformers in the equilibrium revealed the highest repulsion between the 3-allyloxy group and the isopropoxy aglycon and its dependence on the solvent polarity. Differences in the conformational behavior of 3-<i>O</i>-allyl and 3-<i>O</i>-acetyl-α-d-idopyranoside derivatives complied with the notion that higher electron density on O-3 increased 1,3-<i>syn</i>-diaxial repulsion. 3-<i>O</i>-TBDPS derivative existed mainly in ⁴<i>C</i>₁ conformation. The attenuation of the 1,3-<i>syn</i>-diaxial repulsive interaction indicates that TBDPS has stereoelectronic properties that may have significance in context of fixing unnatural pyranoside conformation with the help of silyl groups but have been disregarded until now

Combination of 3‑<i>O</i>‑Levulinoyl and 6‑<i>O</i>‑Trifluorobenzoyl Groups Ensures α‑Selectivity in Glucosylations: Synthesis of the Oligosaccharides Related to <i>Aspergillus fumigatus</i> α‑(1 → 3)‑d‑Glucan

Stereospecific α-glucosylation of primary and secondary OH-group at carbohydrate acceptors is achieved using glucosyl N-phenyl-trifluoroacetimidate (PTFAI) donor protected with an electron-withdrawing 2,4,5-trifluorobenzoyl (TFB) group at O-6 and the participating levulinoyl (Lev) group at O-3. New factors have been revealed that might explain α-stereoselectivity in the case of TFB and pentafluorobenzoyl (PFB) groups at O-6. They are of conformational nature and confirmed by DFT calculations. The potential of this donor, as well as the orthogonality of TFB and Lev protecting groups, is showcased by the synthesis of α-(1 → 3)-linked pentaglucoside corresponding to Aspergillus fumigatus α-(1 → 3)-d-glucan and of its hexasaccharide derivative, bearing β-glucosamine residue at the non-reducing end

Evidence for Inhibition of Lysozyme Amyloid Fibrillization by Peptide Fragments from Human Lysozyme: A Combined Spectroscopy, Microscopy, and Docking Study

Degenerative diseases, such as Alzheimer’s and prion diseases, as well as type II diabetes, have a pathogenesis associated with protein misfolding, which routes with amyloid formation. Recent strategies for designing small-molecule and polypeptide antiamyloid inhibitors are mainly based on mature fibril structures containing cross β-sheet structures. In the present study, we have tackled the hypothesis that the rational design of antiamyloid agents that can target native proteins might offer advantageous prospect to design effective therapeutics. Lysozyme amyloid fibrillization was treated with three different peptide fragments derived from lysozyme protein sequence R¹⁰⁷–R¹¹⁵. Using low-resolution spectroscopic, high-resolution NMR, and STD NMR-restrained docking methods such as HADDOCK, we have found that these peptide fragments have the capability to affect lysozyme fibril formation. The present study implicates the prospect that these peptides can also be tested against other amyloid-prone proteins to develop novel therapeutic agents

Novel mouse monoclonal antibodies specifically recognize <i>Aspergillus fumigatus</i> galactomannan

<div><p>A panel of specific monoclonal antibodies (mAbs) against synthetic pentasaccharide β-D-Gal<i>f</i>-(1→5)-[β-D-Gal<i>f</i>-(1→5)]₃-α-D-Man<i>p</i>, structurally related to <i>Aspergillus fumigatus</i> galactomannan, was generated using mice immunized with synthetic pentasaccharide-BSA conjugate and by hybridoma technology. Two selected mAbs, 7B8 and 8G4, could bind with the initial pentasaccharide with affinity constants of approximately 5.3 nM and 6.4 nM, respectively, based on surface plasmon resonance-based biosensor assay. The glycoarray, built from a series of synthetic oligosaccharide derivatives representing different galactomannan fragments, demonstrated that mAb 8G4 could effectively recognize the parental pentasaccharide while mAb 7B8 recognizes its constituting trisaccharide parts. Immunofluorescence studies showed that both 7B8 and 8G4 could stain <i>A</i>. <i>fumigatus</i> cells in culture efficiently, but not the mutant strain lacking galactomannan. In addition, confocal microscopy demonstrated that <i>Candida albicans</i>, <i>Bifidobacterium longum</i>, <i>Lactobacillus plantarum</i>, and numerous gram-positive and gram-negative bacteria were not labeled by mAbs 7B8 and 8G4. The generated mAbs can be considered promising for the development of a new specific enzyme-linked assay for detection of <i>A</i>. <i>fumigatus</i>, which is highly demanded for medical and environmental controls.</p></div

Investigation of oligosaccharide specificity of mAbs 7B8 and 8G4 using ELISA.

<p>(A) Composition of thematic glycoarray built using oligosaccharide ligands representing key structural elements of <i>A</i>. <i>fumigatus</i> galactomannan chain, and (B) assay for carbohydrate specificity of 7B8 and 8G4 mAbs.</p

Binding of fungal and bacterial cultures with mAbs 7B8 and 8G4.

<p>(A) Sandwich enzyme-linked immunosorbent assay (ELISA) with 7B8 mAb: the wells of microtiter plates were coated with 7B8 mAb and incubated with serial dilutions of microbial supernatants; ELISA was performed with horseradish peroxidase-conjugated 7B8 mAb. (B) Sandwich ELISA with 8G4 mAb: the wells of microtiter plates were coated with 8G4 mAb and incubated with serial dilutions of microbial supernatants; ELISA was performed with horseradish peroxidase-conjugated 8G4 mAb.</p

Structure of <i>Aspergillus fumigatus</i> galactomannan and its synthetic analogs.

<p>(A) Structural fragments of <i>A</i>. <i>fumigatus</i> galactomannan (summarized from refs. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193938#pone.0193938.ref006" target="_blank">6</a>] and [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193938#pone.0193938.ref008" target="_blank">8</a>]). (B) Pentasaccharide <b>GM-1</b> and its BSA <b>(GM-1-BSA)</b> and biotinylated <b>(GM-1-Biot)</b> conjugates used in mice immunization and mAb screening. The carbohydrate sequences are represented according to symbol carbohydrate nomenclature [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193938#pone.0193938.ref026" target="_blank">26</a>].</p

Specific binding of mAbs 7B8 and 8G4 with <i>A</i>. <i>fumigatus</i>, <i>A</i>. <i>flavus</i>, and <i>C</i>. <i>albicans</i>.

<p>Cells were grown in Sabouraud broth, fixed, and incubated with mAbs 7B8 and 8G4. Binding of mAbs with fungal cells was detected with Alexa Fluor 488-conjugated anti-mouse IgG antibody staining in (A) confocal microscopy, and (B) DIC microscopy. Scale bar = 10 μm.</p

Effect of polysaccharide preparations on tumor growth and angiogenesis <i>in vivo</i>.

<p>C57BL/6 (B6) mice were injected with 500 µl of Matrigel containing 1×10⁵ B16-F10 cells in PBS or 100 µg of a non-fractionated polysaccharide mixture <b>L.s.-P</b> or its fractions <b>L.s.-1.0</b> and <b>L.s.-1.25</b>. After 6–7 days, tumors were removed and hemoglobin content was evaluated by using the Drabkin colorimetric method. Results are expressed as the amount of hemoglobin (mg)/Matrigel weight (mg) (<b>A</b>) (**<i>P</i><0.01). (<b>B</b>) Flow cytometry analysis of the frequency of CD34⁺ endothelial cells on Matrigel plugs embedded with B16 melanoma cells. (**<i>P</i><0.01) (<b>C</b>) <i>In vitro</i> cell growth of B16 melanoma cells exposed to 100 µg/ml of <b>L.s.-P</b> or its fractions <b>L.s.-1.0</b> and <b>L.s.-1.25</b>. Data are the mean ± SEM of three independent experiments. (<b>D</b>) B6 mice were injected with 500 µl Matrigel containing 1×10⁵ B16-F10 cells. <b>L.s.-P</b> or its fractions <b>L.s.-1.0</b> and <b>L.s.-1.25</b> were injected <i>i.p.</i> at doses of 50 mg/kg every 3 days and compared to control (PBS). Tumors were removed on day 21 post-implantation, photographed (<b>D</b>) and analyzed for CD31⁺ associated blood vessels (<b>E</b>), microvessel density (<b>F</b>) and weight (<b>G</b>). (*<i>P</i><0.05; **<i>P</i><0.01).</p