Complex Bi Research Articles

Glycomics of cervicovaginal fluid from women at risk of preterm birth reveals immuno-regulatory epitopes that are hallmarks of cancer and viral glycosylation

During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1β, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women’s health.

Site‐specific N‐glycan profiles of α5β1 integrin from rat liver

Like most other cell surface proteins, α5 β1 integrin is glycosylated, which is required for its various activities in ways that mostly remain to be determined. Here, we have established the first comprehensive site-specific glycan map of α5 β1 integrin that was purified from a natural source, that is, rat liver. This analysis revealed striking site selective variations in glycan composition. Complex bi, tri, or tetraantennary N-glycans were predominant at various proportions at most potential N-glycosylation sites. A few of these sites were nonglycosylated or contained high mannose or hybrid glycans, indicating that early N-glycan processing was hindered. Almost all complex N-glycans had fully galactosylated and sialylated antennae. Moderate levels of core fucosylation and high levels of O-acetylation of NeuAc residues were observed at certain sites. An O-linked HexNAc was found in an EGF-like domain of β1 integrin. The extensive glycan information that results from our study was projected onto a map of α5 β1 integrin that was obtained by homology modeling. We have used this model for the discussion of how glycosylation might be used in the functional cycle of α5 β1 integrin. A striking example concerns the involvement of glycan-binding galectins in the regulation of the molecular homeostasis of glycoproteins at the cell surface through the formation of lattices or endocytic pits according to the glycolipid-lectin (GL-Lect) hypothesis. We expect that the glycoproteomics data of the current study will serve as a resource for the exploration of structural mechanisms by which glycans control α5 β1 integrin activity and endocytic trafficking. Glycosylation of α5 β1 integrin has been implicated in multiple aspects of integrin function and structure. Yet, detailed knowledge of its glycosylation, notably the specific sites of glycosylation, is lacking. Furthermore, the α5 β1 integrin preparation that was analyzed here is from a natural source, which is of importance as there is not a lot of literature in the field about the glycosylation of "native" glycoproteins.

Geology of the Frontino-Morrogacho Gold Mining District and Metallogeny of the El Cerro Igneous Complex

The Frontino-Morrogacho gold district is located on the western flank of the Western Cordillera, NW of Antioquia Province. Gold mineralizations in the area are spatially and genetically associated with the cooling of three mid- to late-Miocene age intrusive centers in the form of stocks and dikes (12-9 Ma): Cerro Frontino, La Horqueta and Morrogacho (El Cerro Igneous Complex). These composite magmatic pulses, with ultramafic to intermediate compositions, vary into diorite-, gabbro- and monzonitic-bearing phases. Mineralization in the complex is present as several structurally controlled fault veins, shear-related veins, sheeted quartz extension veins and quartz-carbonate tabular extension veins, with the development of swarms and nests of veins-veinlets, breccias and stockworks. Structures range from centimeter-wide individual veinlets to several meter-wide swarms of veins developed within broad mineralized structural corridors, with a metallic signature that consists of Au + Ag + Cu + Zn + Pb + As (± Te ± Bi ± Sb ± Hg ± W) assemblages. Veins are composed of multiple stages of mineralization, and the formation of these structures is enhanced by the presence of a local regime of extension and E-trending structures, including evidence of faults and shear zones with right-lateral displacement, which are likely involved in pluton emplacement and cooling. The ore mineralogy is composed of pyrrhotite, pyrite, chalcopyrite, sphalerite, galena and arsenopyrite assemblages formed in two or more mineralization stages, with complex Bi, Te, Sb and Hg mineral specimens associated with Au and Ag. Mineralized structures of the district present a preferential E-strike with dominant vertical to subvertical and occasional subhorizontal S-dips and secondary N- and NW-strikes that are steep to vertically E-dipping.
 The Frontino-Morrogacho Gold district presents characteristics related to the architecture, mineralogy and alteration of reduced (ilmenite-series) intrusion-related gold systems but is genetically associated with a parental oxidized magma source. The gold content is associated with three different families involving electrum, tellurides and alloys: gold rich (66 to 78% Au, 22 to 34% Ag), average (50 to 60% Au, 40 to 50% Ag) and silver rich (32 to 40% Au, 60 to 68% Ag). The formation of these bodies is associated with an N-S magmatic-metallogenic trend of Au-Ag-Cu deposits, which extend for more than 300 km along the Western Cordillera of Colombia. Similar plutonic suites span from the south of Chocó Province to the north of Antioquia Province, which indicates that the Frontino-Farallones-Botón arc can be proposed as an individual metallogenic belt.

β-like FeOOH Nanoswords Activated by Ni Foam and Encapsulated by rGO toward High Current Densities, Durability, and Efficient Oxygen Evolution.

As an alternative to the oxygen evolution reaction (OER) electrocatalyst developed by a complex bi- or multimetal ion with layered double hydroxide (LDH) structures, we design a simple, self-supported, and single-metal-ion OER electrocatalyst having lower overpotentials and high current densities in alkaline water electrolyzers. Here, β-like FeOOH nanosword structures encapsulated by reduced graphene oxide (rGO) were cost-effectively synthesized on formable Ni foam substrates as an efficient and highly durable OER catalyst. It is revealed that the rGO uniformly covered the β-like FeOOH nanoswords to form a porous network achieving a lower overpotential of only 210 mV at 10 mA cm-2 with a stable operation for more than 40 h in alkali media. Moreover, a high current density of ∼300 mA cm-2 was achieved at less than 1.8 V. In-depth physical and electrochemical analysis indicated that the intrinsic charge transfer through activated Ni-foam, β-like phase, and nanosword morphology was evidently beneficial for enhancing the OER activity of the bare FeOOH, and its encapsulation by rGO further improved the conductivity and long-life durability. Our integrated OER electrocatalyst developed by a simple method (repeated soaking and quenching process) will aid in scaling up β-like FeOOH nanoswords for preparing uniform and large-area electrodes for industrial purposes.

Study of the Anticancer Activity of a New Nanosize Bismuth(V)-Based Coordination Complex Against Human Bone Tumor Cells

Herein we report a new bismuth(V)-based coordination complex Bi(phenyl)3(2,5-dfa)2 (1) that has been successfully prepared by using C donor phenyl ring and O donor 2,5-difluorobenzoic acid (2,5-H2dfa) ligands. The coordination complex has been comprehensively characterized by single crystal X-ray diffraction, Powder X-ray diffraction and thermogravimetric analysis. Finally, an evaluation of cytotoxicity against human OS-732 bone tumor cell lines for the synthesized nanoparticles was performed. A new bismuth(V)-based coordination complex Bi(phenyl)3(2,5-dfa)2 (1) has been successfully prepared and evaluation of cytotoxicity against human OS-732 bone tumor cell lines for its related nanoparticles was performed.

Comparative Analysis of Two BI Tools: Micro Strategy and Tableau

The need for enterprise business intelligence initiatives has skyrocketed due to the potential to empower businesses to make better data driven decisions. Better insights are being needed by business users into core business problems as they need access to these insights faster than ever before. Many BI vendors have provided feasible options to buyer looking to implement BI solution. It is difficult for a business person to reach any one decision when given a variety of options.BI previously had merely reporting capabilities, BI solutions have progressively acquired drastic functionality, like data mining, improved analytics tools, and online analytical processing (OLAP) services, with various company mergers and acquisitions, and the BI field has evolved to more complex and heavy BI solutions.Two widely used BI-tools for reporting and providing business insights are MicroStrategy and Tableau. MicroStrategy is well known for its software which is based on single code base, it is suitable for applications of all sizes; grips hardware, operating system, and data source infrastructure while making BI more accessible for business users. Tableau supports ad hoc analysis for the day to day user, it facilitates the business users to better visualize and understand their data. Also, for easy consumption, it allows to display the KPIs easily on a centralized analytics platform.

Physicochemical Conditions of Formation for Bismuth Mineralization Hosted in a Magmatic-Hydrothermal Breccia Complex: An Example from the Argentine Andes

The San Francisco de los Andes breccia-hosted deposit (Frontal Cordillera, Argentina) is characterized by complex Bi–Cu–Pb–Zn–Mo–As–Fe–Ag–Au mineralization. After magmatic-hydrothermal brecciation, tourmaline and quartz partially cemented open spaces, followed by quiescent periods where Bi–Cu–Pb–Zn ore formed. Bismuth ore precipitation is characterized by Bi-sulfides, sulfosalts, and tellurosulfide inclusions, which temporally co-exist with Ag-telluride inclusions and chalcopyrite. Three distinct Bi mineralizing stages have been defined based on the following mineral assemblages: (1) Bismuthinite (tetradymite–hessite inclusions); (2) Bismuthinite (tetradymite–hessite inclusions) + cosalite (tetradymite inclusions) + chalcopyrite; and (3) Cosalite (tetradymite inclusions) + chalcopyrite. Overall, Ag-poor bismuthinite hosts both Bi-tellurosulfide and Ag-telluride inclusions, whereas Ag-rich cosalite only hosts tetradymite inclusions.

Multicomponent, Enantioselective Michael-Michael-Aldol-β-Lactonizations Delivering Complex β-Lactones.

Optically active, tertiary amine Lewis bases react with unsaturated acid chlorides to deliver chiral, α,β-unsaturated acylammonium salts. These intermediates participate in a catalytic, enantioselective, three-component process delivering bi- and tricyclic β-lactones through a Michael-Michael-aldol-β-lactonization. In a single operation, the described multicomponent, organocascade process forms complex bi- and tricyclic β-lactones by generating four new bonds, two rings, and up to four contiguous stereocenters. In the racemic series, yields of 22-75% were achieved using 4-pyrrolidinopyridine as Lewis base. In the enantioselective series employing isothiourea catalysts, a kinetic resolution of the initially formed racemic Michael adduct appears operative, providing yields of 46% to quantitative (based on 50% max) with up to 94:6 er. Some evidence for a dynamic kinetic asymmetric transformation for tricyclic-β-lactone 1d was obtained following optimization (yields up to 61%, 94:6 er) through a presumed reversible Michael.

Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y.

Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases.

Atom probe tomography evidence for uniform incorporation of Bi across the growth front in GaAs1−xBix/GaAs superlattice

The three-dimensional distribution of Bi atoms in a GaAs1−xBix/GaAs superlattice grown by metalorganic vapor phase epitaxy (MOVPE) was studied using atom probe tomography (APT). The Bi distribution in the growth direction deduced from APT agreed quantitatively with the complex Bi concentration profile that was discovered using high-angle annular dark-field scanning transmission electron microscopy in a previous study. More importantly, APT revealed the Bi atom distribution in the growth planes at near atomic resolution. Bi nearest neighbor distribution and concentration frequency distribution analysis of the APT data indicated a statistically random distribution of Bi atoms in 1–2nm thick layers oriented perpendicular to the growth direction. These results provide evidence that Bi is incorporated homogeneously across the growth front even when the concentration profile in the growth direction is complex. They also suggest that MOVPE growth conditions can promote uniform Bi distribution within GaAs1−xBix layers, opening a path for application of these materials in the optoelectronic devices for which they show much promise.

The complexation features of xylenol orange with Bi(III) and its spectrophotometric determination in pharmaceuticals

The complexation features of Bi(III) with xylenol orange (XO) have been studied. It was found that three complexes of different stoichiometry have been formed in the studied system. The complex composition of Bi(III) : XO = 1 : 1 (λ = 540 nm, ε = 17000, log β = 10.5) has been formed at pH = 1.0 in reagent excess, and its dimerization with the formation of the complex stoichiometry 2 : 2 (λ = 560 nm, ε = 24000, log β = 17.8) has been observed in excess of Bi (III). The complex composition of Bi(III) : XO = 1 : 2 has been formed with weak light absorbing properties (λ = 500 nm, ε = 9000, log β = 9.9) at pH = 6.8. The complexation mechanism of Bi(III) with XO has been proposed based on the totality of the spectrophotometric data and its theoretical interpretations. In the acidic environment (pH = 1.0) the coordinating ion is Bi 3+ and coordinated ligand is an ionized by sulfo-groups reagent form. At pH = 6.8, the ion chelator is BiOH 2+ , and XO reacts in ionized by sulfo and carboxyl groups form. The effect of extraneous ions on the absorbance value of the complex Bi (III) with a XO at pH = 1.0 was studied. The complex with molar ratio 1 : 1 is recommended as an analytical form. Beer’s law holds in the Bi(III) concentrations range 0.4-10.0 μ g/cm 3 . The detection limit is 0.12 μ g/cm 3 and the limit of quantification is 0.37 μ g/cm 3 . The simple method of spectrophotometric determination of Bi(III) with xylenol orange in pharmaceuticals has been developed. Keywords : spectrophotometric analysis, complexation, xylenol orange, bismuth (III), pharmaceuticals (Russian) DOI: http://dx.doi.org/10.15826/analitika.2016.20.3.007 A.N. Chebotarev, D.V. Snigur , V.P. Dubovyiy Odessa I.I. Mechnikov National University ul. Dvorianskaya, 2, Odessa, Ukraine , 65082

Single source precursor approach to the synthesis of Bi2S3 nanoparticles: A new amperometric hydrogen peroxide biosensor

Bi2S3 nanoparticles (NPs) are synthesized from a single source precursor complex Bi(ACDA)3 (HACDA=2-aminocyclopentene-1-dithiocarboxylic acid) through a simple solvothermal decomposition process. The precursor complex is characterized by several spectroscopic techniques (FTIR, UV–vis spectroscopy) and finally the structure has been determined by single crystal X-ray diffraction study suggesting an unusual distorted pentagonal pyramidal geometry. The transmission electron microscopic (TEM) study ascertains the NPs to be of rod-like structure with a diameter of approximately 10–40nm and a wide range of edge lengths from 50nm to 300nm. These NPs, immobilized on surface of a glassy carbon electrode (GCE), show high electron transfer ability and good electrochemical behavior and also exhibit electro-catalytic activity toward the reduction of hydrogen peroxide. As a result, this Bi2S3 NPs have been employed as a new H2O2 biosensor for amperometric estimation of H2O2 in a linear range from 10 to 5000μM. In addition to high stability, the present biosensor has good relative standard deviation (RSD=3.2%) and detection limit (DL of 2.5μM at 3σ).

Influence of La3+ Substitution on Electrical and Photocatalytic Behavior of Complex Bi2Sn2O7 Oxides

Pyrochlore-type Bi2–xLaxSn2O7 (0.0 ≤ x ≤ 0.20) system has been explored for its facile synthesis and electrical and photocatalytic functionalities. The highly distorted α-polymorph of Bi2Sn2O7 was synthesized, and successive La3+ substitutions were found to increase the lattice symmetry. Electric field dependent polarization measurements showed the ferroelectric hysteresis loop for pure Bi2Sn2O7 for the first time, and La3+ substitution was found to have a bearing on the ferroelectric properties with concomitant increase in leakage current. Temperature-dependent polarization studies were also performed on various nominal compositions. Diffuse reflectance spectroscopy established the tenability of the band gap as the function of La3+ content (2.5–3.0 eV). In order to explore the multifunctionality of this unique bismuth-containing system, the photocatalytic dye degradation of rhodamine B was investigated with Bi2–xLaxSn2O7 (0.0 ≤ x ≤ 0.20) system in both UV and visible regions. The variation in band gap introduced La3+ substitution significantly enhanced the photocatalytic behavior of bismuth stannate for rhodamine B degradation. The rate constant for the nominal composition Bi1.85La0.15Sn2O7 (17.6 × 10–2 min–1) is 6-fold the value for the pure Bi2Sn2O7 (2.75 × 10–2 min–1). The degradation profiles of rhodamine B in the UV and visible regions showed that dye degradation proceeds through different mechanisms which are discussed. The present study attempts to give an insight into the variation in electrical and photocatalytic properties and relate them to changes in structure. Bi2–xLaxSn2O7 (0.0 ≤ x ≤ 0.20) system is being proposed here as multifunctional candidates for lead-free electrical materials and efficient photocatalyst in the UV and visible regions.

Structure of bismuth(III) complexes with thiourea according to EXAFS spectroscopy Data

The EXAFS and XANES spectra of the solid complex Bi(tu)6(ClO4)3 (1) (tu is thiourea) and the solutions 0.1 M Bi(ClO4)3 + 1.8 M tu + 1 M HClO4 (2) and 0.05 M Bi(ClO4)3 + 1.5 M tu + 1 M HClO4 (3) were recorded. For solid [Bi(tu)6](ClO4)3, it was found that the first coordination shell of the Bi atom contains six sulfur atoms at distances of ∼2.7–2.9 A. It was assumed that binuclear bismuth complexes with Bi-S distances of ∼2.8 and ∼3.3 A formed in Bi(ClO4)3 + (tu) + HClO4 solutions.

Pyrite–sulfosalt reactions and semimetal fractionation in the Chinkuashih, Taiwan, copper–gold deposit: a 1 Ma paleo‐fumarole

AbstractThe mineralized fracture system that underlay paleo‐fumarole field at Chinkuashih, Taiwan has been exposed by copper–gold mining to depths of about 550 m below the paleo‐surface. Its mineralogy and systematic variations in metal and semimetal (Fe, Cu, As, Sb, Bi, Hg, Cd, Sn, Zn, Pb, Se, Te, Au, Ag) concentrations provide insights into the chemical responses of a magmatic‐vapor phase as it expands through fracture arrays to the surface and discharges as fumaroles associated with more extensive solfatara. At Chinkuashih, following initial sealing of the fractures by silica‐alunite alteration, brittle failure reestablished discharge from an underlying reservoir of magmatic vapor. Crystalline pyrite was deposited first in the fractures and was succeeded and replaced by ‘enargite’ (Cu3(As,Sb)S4) as sulfosalt encrustations (‘sublimate’) on fracture surfaces and in extensional cracks. Subsequent recrystallization resulted in complex exsolution intergrowths with antimony fractionation to the evolving crystal–vapor interface. Heavy metal fractionation between sulfosalt and vapor enriched the vapor phase in heavy metals that subsequently precipitated as complex Bi–Hg–Sn sulfosalts in discrete areas (paleo‐fumaroles) close to the paleo‐surface in a manner analogous to modern‐day fumaroles on active volcanoes such as Vulcano, Italy. As in similar paleo‐fumaroles (e.g., El Indio, Chile and Lepanto, Philippines), the most characteristic reaction sequence is the partial replacement of the early pyrite by enargite and Fe‐tennantite. It is proposed that this reaction tracks the decrease in the pressure of the underlying magmatic‐vapor reservoir because of the sustained discharge of vapor to the surface.

Induction of IgA Deposits and Glomerulonephritis by IgA Rheumatoid Factor

Induction of IgA Deposits and Glomerulonephritis by IgA Rheumatoid Factor

DTPA complexation of bismuth in human blood serum

The in vivo(212)Pb/(212)Bi generator is promising for application in targeted alpha therapy (TAT) of cancer. One main limitation of its therapeutic application is due to potential release of (212)Bi from the radioconjugate upon radioactive decay of the mother nuclide (212)Pb, potentially leading to irradiation of healthy tissue. The objective of the present work is to assess whether the chelate CHX-A''-DTPA (N-(2-aminoethyl)-trans-1,2-diaminocyclohexane-N,N',N''-pentaacetic acid) bound to a biological carrier molecule may be able to re-complex released (212)Bi under in vivo conditions to limit its translocation from the target site. CHX-A''-DTPA was bound to bovine gamma globulin (BGG) to mimic a model conjugate and the stability of the Bi-CHX-A''-DTPA-BGG conjugate was studied in blood serum by ultrafiltration. TRLFS experiments using Cm(III) as a fluorescent probe demonstrated that linking CHX-A''-DTPA to BGG does not affect the coordination properties of the ligand. Furthermore, comparable stability constants were observed between Bi(III) and free CHX-A''-DTPA, BGG-bound CHX-A''-DTPA and DTPA. The complexation constants determined between Bi(III) and the chelate molecules are sufficiently high to allow ultra trace amounts of the ligand to efficiently compete with serum transferrin controlling Bi(III) speciation in blood plasma conditions. Nevertheless, CHX-A''-DTPA is not able to complex Bi(III) generated in blood serum because of the strong competition between Bi(III) and Fe(II) for the ligand. In other words, CHX-A''-DTPA is not "selective" enough to limit Bi(iii) release in the body when applying the (212)Pb/(212)Bi in vivo generator.

Reply to Mangold and Ankersmit

We appreciate the comments [1] of Drs Mangold and Ankersmit on our article [2]. Our group proved that genipin fixation is a novel alternative to conventional glutaraldehyde fixation, and the addition of decellularization, organic solvent treatment and detoxification prevent calcification of glutaraldehyde/genipinfixed bovine pericardium. We also found that the titer of anti-α-Gal(Galα1-3Galβ1-4GlcNAc-R) antibodies (immunoglobulin G) increases after the implantation of bovine pericardium to rabbit, and in vivo calcification results are consistent with the increase in anti-α-Gal antibodies titer [2]. Although the cause and significance of the xenoreactive antibody response between the different species in α-Gal concordant animal model have not been exactly known, some possible suggestions may exist: (i) by a species-specific expression of these conjugated compounds including α-Gal epitopes; (ii) a tissue-specific expression of these conjugated compounds including α-Gal epitopes and (iii) the differences in the fine specificity of natural anti-Gal antibodies in various species which recognize various ‘facets’ of the α-Gal epitope in its three-dimensional form. A species-specific expression of these conjugated compounds including α-Gal epitopes has been well demonstrated for so long. Thyroglobulin, fibrinogen and immunoglobulins from various species express varying amounts of Galα1-3Galβ14GlcNAc residues between 0.01 and 11 residues per molecule [3]. Rabbit red blood cells contain a range of glycolipids of varying lengths that terminate with the Galα1-3Galβ1-4GlcNAc-R structure. These glycolipids vary in size by increments of five monosaccharides, and each increment forms an additional branch. Although rat did not contain Galα1-3Galβ1-4GlcNAc neutral glycosphingolipids in the kidney, pig and sheep contained sialic acid-containing glycolipids (gangliosides) with the Galα1-3Galβ1-4GlcNAc-R structure, most likely the same branched, ganglioside identified in bovine red blood cells [4]. Thymus tissue from sheep, pig and rabbit also contained a range (compounds with 5–11 sugars) of neutral glycolipids terminating with the Galα1-3Galβ1-4GlcNAc-R structure demonstrating a species-specific expression of these compounds. Although the kidney and thymus from sheep, pig and rabbit express Galα1-3Galβ1-4GlcNAc-R glycolipids, these glycolipids were not detected in brain tissue demonstrating a tissue-specific expression of these compounds [5]. The detailed analysis of N-linked glycans from porcine kidney demonstrated that Galα1-3Galβ14GlcNAc-R termini were found on a variety of complex bi-, triand tetra-antennary N-glycans [6]. As we evaluated recently the immune response in the implantation of bovine pericardium to mice in which the α1,3-galactosyltransferase gene was knocked out (Gal/ mice), the titer of anti-α-Gal antibodies much increased. But interestingly, we also observed the increase in anti-α-Gal antibodies in wild-type mouse and rat as well as rabbit, although much less than Gal/ mice. We think that further transplantation or implantation experiments are needed to validate more exact xenoreactive immunologic responses between the different species.

Kinetic study of 2-butanol O-acylation and sec-butylamine N-acylation catalyzed by Candida antarctica lipase B

The aim of this work was to study the differential behavior shown by Candida antarctica lipase B during the O-acylation and N-acylation of monofunctional alcohols and monofunctional amines. To achieve this, 2-butanol and sec-butylamine were used as model molecules. Yields, kinetics and enantioselectivity were studied for both reactions. Although a steady-state ordered ternary complex bi–bi mechanism was obtained for the O-acylation of 2-butanol, a ping–pong bi–bi mechanism was obtained for the N-acylation in case of low sec-butylamine concentrations. The values of apparent kinetic parameters were calculated: the enantiomeric ratios (E) were evaluated and confirmed the preference of C. antarctica lipase B for the (R)-enantiomer, which was consistent with the literature. The enantioselectivity was calculated for the alcohol (E ≈ 3.17) and for the amine (E ≈ 1.34). Concerning the O-acylation, the yields were found to be very similar for both enantiomers R and S. However, both initial rates and yields of the (R)-enantiomer N-acylation were higher than those of the (S)-enantiomer. In the last part of our study, the chemoselectivity of C. antarctica lipase B was evaluated, showing that C. antarctica lipase B was a chemoselective enzyme that preferentially catalyzed the O-acylation to the detriment of the N-acylation (C ≈ 92, for the selective acylation of (R)-enantiomers). These results provide new insights for the synthesis of products issued from the selective acylation of multifunctional substrates such as amino-alcohols.

Alterations in Glycopeptides Associated with Herceptin Treatment of Human Breast Carcinoma MCF-7 and T-Lymphoblastoid Cells

The therapeutic humanized monoclonal antibody IgG1 known as Herceptin® has shown remarkable antitumor effects. Although this type of therapy has increased the cancer-free survival of patients, not all tumors respond to this treatment and cancers often develop resistance to the antibody. Despite the fact that Herceptin function has been extensively studied, the precise mechanism underlying its antitumor activity still remains incompletely defined. We previously demonstrated on human breast MCF-7 carcinoma and T-lymphoblastoid CEM cells that monoclonal antibody in combination with Lipoplex consisting of Lipofectamine mixed with plasmid DNA showed a more profound effect on cancer cell viability than antibody alone. The analyses of N-glycans isolated from cancer cells showed dramatic differences in profiles when cells were exposed to Herceptin. Moreover, the investigation of glycosylated peptides from the same cancer cell models after treatment revealed further alterations in the post-translational modifications. Tandem mass spectra obtained from the samples treated confirmed the presence of a series of glycopeptides bearing characteristic oligosaccharides as described in IgG1. However some of them differed by mass differences that corresponded to peptide backbones not described previously and more of them were detected from Herceptin treated samples than from cells transfected with Heceptin/Lipoplex. The results indicate that the presence of Lipoplex prevents antibody transformation and elongates its proper function. The better understanding of the multipart changes described in the glycoconjugates could provide new insights into the mechanism by which antibody induces regression in cancers.