Neutral Core Research Articles

Siglec-7 Undergoes a Major Conformational Change When Complexed with the α(2,8)-Disialylganglioside GT1b

The siglecs are a group of mammalian sialic acid binding receptors expressed predominantly in the immune system. The CD33-related siglecs show complex recognition patterns for sialylated glycans. Siglec-7 shows a preference for alpha(2,8)-disialylated ligands and provides a structural template for studying the key interactions that drive this selectivity. We have co-crystallized Siglec-7 with a synthetic oligosaccharide corresponding to the alpha(2,8)-disialylated ganglioside GT1b. The crystal structure of the complex offers a first glimpse into how this important family of lectins binds the structurally diverse gangliosides. The structure reveals that the C-C' loop, a region implicated in previous studies as driving siglec specificity, undergoes a dramatic conformational shift, allowing it to interact with the underlying neutral glycan core of the ganglioside. The structural data in combination with mutagenesis studies show that binding of the ganglioside is driven by extensive hydrophobic contacts together with key polar interactions and that the binding site structure is complementary to preferred solution conformations of GT1b.

Glycosylation of an immunoglobulin produced from a murine hybridoma cell line: The effect of culture mode and the anti‐apoptotic gene, bcl‐2

The impact of bcl-2 over-expression on the glycosylation pattern of an antibody produced by a bcl-2 transfected hybridoma cell line (TB/C3.bcl-2) was investigated in suspension batch, continuous and high cell density culture (Flat hollow fibre, Tecnomouse system). In all culture modes bcl-2 over-expression resulted in higher cell viability. Analysis of the glycans from the IgG of batch cultures showed that >95% of the structures were neutral core fucosylated asialo biantennary oligosaccharides with variable terminal galactosylation (G0f, G1f and G2f) consistent with previous analysis of glycans from the conserved site at Asn-297 of the IgG protein. The galactosylation index (GI) was determined as an indicator of the glycan profile (=(G2 + 0.5* G1)/(G0 + G1 + G2)). GI values in control cultures were comparable to bcl-2 cultures during exponential growth (0.53) but declined toward the end of the culture when there was a loss in cell viability. Low dilution rates in chemostat culture were associated with reduced galactosylation of the IgG glycans in both cell lines. However, at the higher dilution rates the GI for IgG was consistently higher in the TB/C3.bcl-2 cultures. In the hollow fibre bioreactor the galactosylation of the IgG glycans was considerably lower than in suspension batch or continuous cultures with GI values averaging 0.38. Similar low galactosylation values have been found previously for high density cell cultures and these are consistent with the low values obtained when the dissolved oxygen level is maintained at a low value (10%) in controlled suspension cultures of hybridomas.

Hen Egg Yolk Low-Density Lipoproteins Film Spreading at the Air−Water and Oil−Water Interfaces

Hen egg yolk is largely used as an ingredient in food emulsions due to its exceptional emulsifying properties. Low-density lipoproteins (LDL) are the main egg yolk constituents and the most important contributors to yolk emulsifying properties. To better understand the LDL adsorption mechanism and spreading at the interface, we extracted and studied LDL at different interfaces. At the air-water interface, the LDL film isotherm presents three transitions, and two were identified by each lipid class present in LDL. The last transition should be due to apoproteins-lipids complexes. During LDL adsorption, the presence of apoproteins at the LDL surface and the neutral lipid core is necessary. At pH 3 and pH 7, LDL are disrupted and spread quasi-similarly at the air-water interface, contrary to the oil-water interface where LDL spread more at pH 7 than at pH 3.

Mapping CTTS dynamics of Na−in tetrahydrofurane with ultrafast multichannel pump–probe spectroscopy

Using multichannel femtosecond spectroscopy we have followed Na- charge transfer to solvent (CTTS) dynamics in THF solution. Absorption of the primary photoproducts in the visible, resolved here for the first time, consists of an asymmetric triplet centered at 595 nm, which we assign to a metastable incompletely solvated neutral atomic sodium species. Decay of this feature within approximately 1 ps to a broad and structureless solvated neutral is accompanied by broadening and loss of spectral detail. Kinetic analysis shows that both the spectral structure and the decay of this band are independent of the excitation photon frequency in the range 400-800 nm. With different pump-probe polarizations the anisotropy in transient transmission has been charted and its variation with excitation wavelength surveyed. The anisotropies are assigned to the reactant bleach, indicating that due to solvent-induced symmetry breaking, the CTTS absorption band of Na- is made up of discreet orthogonally polarized sub bands. None of the anisotropy in transient absorption could be associated with the photoproduct triplet band even at the earliest measurable time delays. Along with the documented differences in the spatial distribution of ejected electrons across the tested excitation wavelength range, these results lead us to conclude that photoejection is extremely rapid, and that loss of correlations between the departing electron and its neutral core is faster than our time resolution of approximately 60 fs.

A Role for the Pregnane X Receptor in High-Density Lipoprotein Metabolism

High-density lipoprotein (HDL) cholesterol is widely recognized as the good plasma cholesterol for coronary heart disease and is believed to be responsible for cholesterol transport from peripheral tissues back to the liver, the central clearing house for cholesterol in the body. Interestingly, the liver is also a major site for HDL production, although the process of particle assembly is believed to occur intravascularly.1–4 ApoA-I is secreted by the liver in lipid-poor form and then interacts with ATP-binding cassette protein A1 (ABCA1) in liver and peripheral tissues to acquire phospholipids and cholesterol, forming a discoidal HDL intermediate sometimes referred to as pre–β-HDL. These particles are excellent substrates for the liver-derived plasma enzyme lecithin:cholesterol acyltransferase. Using the sn-2 fatty acids of the particle-associated phosphatidylcholine, lecithin:cholesterol acyltransferase catalyzes the esterification of cholesterol, which is partially derived from peripheral tissues. This reaction produces the cholesteryl esters (CE) that form the neutral lipid core of the mature spherical HDL particles. In addition to whole HDL particle uptake by the liver, the CE of mature HDL can also be removed by the liver through a process of selective CE uptake via scavenger receptor-class B type I (SR-BI). Both uptake mechanisms result in a directional flux of cholesterol from the plasma compartment to …

SEMI-CLASSICAL PROPAGATION AND SPECTRAL ANALYSIS IN THE H- ION INTERACTING WITH A METALLIC SURFACE

A semi-classical propagator method combined with harmonic inversion of short time signals is used to find the resonant states of an electron interacting with a hydrogen atom near a metallic surface. The atom-electron interaction corresponds to one electron in the presence of a neutral compact core, which can be described by a simple local potential proposed by Cohen. On the other hand, the electron-surface interaction is described by a model proposed by Jennings, the so-called Jelly Model, or by a more realistic local potential that takes into account the shell structure of the metal. A semi-classical propagator approach, proposed by Herman and Kluk, is used to calculate an approximation to the autocorrelation function A(t) = <ψt|ψ0> entirely in terms of classical trajectories. A filter-diagonalization method for harmonic inversion of the complex time signal A(t) is applied to extract the resonances. We verified that the spectral analysis of the signal obtained by semi-classical methods gives satisfactory numerical results for the position and width of the lowest lying resonances.

Selective Formation of MSi16 (M: Sc, Ti, and V).

AbstractFor Abstract see ChemInform Abstract in Full Text.

Selective Formation of MSi16(M = Sc, Ti, and V)

Metal-encapsulated silicon cage clusters are a new class of clusters and are opening up new avenues for silicon-based nanoscale materials. We present experimental evidence for a highly stable cluster corresponding to M@Si16 (M = Sc, Ti, and V). Mass spectrometry and anion photoelectron spectroscopy show that the cluster features an electronically closed TiSi16 neutral core which undergoes a change in the number of valence electrons involving (i) substitution of neighboring metals with Sc and V, or (ii) addition of a halogen atom to the TiSi16 anion, and that VSi16F is predicted to form an ionically bound superatom complex.

Highly Regioselective Synthesis of Amino-Functionalized Dendritic Polyglycerols by a One-Pot Hydroformylation/Reductive Amination Sequence

[reaction: see text] Dendritic architectures with neutral core structures and amines groups in the shell are a synthetic challenge, and there is a need for an efficient access. In this paper, highly selective Rh-catalysts are used for sequential hydroformylation/reductive amination of dendritic perallylated polyglycerols 1 with various amines in a one-pot procedure to give dendritic polyamines 3a-e in high yields (73-99%). In all cases, complete conversion of the allyl ether and aldehyde intermediate has been observed. Furthermore, the use of protected amines provides reactive core-shell-type architectures after deprotection. These soluble but membrane filterable multifunctional dendritic polyamines are of high interest as reagents in synthesis or as supports in homogeneous catalysis as well as nonviral vectors for DNA-transfection.

Polyelectrolyte–surfactant complex: phases of self-assembled structures

We study the structure of complexes formed between ionic surfactants (SF) and a single oppositely charged polyelectrolyte (PE) chain. For our computer simulation we use the ``primitive'' electrolyte model: while the polyelectrolyte is modeled by a tethered chain of charged hard sphere beads, the surfactant molecules consist of a single charged head bead tethered to a tail of tethered hard spheres. A hydrophobic attraction between the tail beads is introduced by assuming a Lennard-Jones potential outside the hard-sphere diameter. As a function of the strengths of both the electrostatic and the hydrophobic interactions, we find the following scenario: switching on and increasing the electrostatic forces first leads to a stretching of the PE and then by condensation of SF to the formation of a complex. For vanishing hydrophobic forces this complex has the architecture of a molecular bottle-brush cylindrically centered around the stretched PE molecule. Upon increasing the hydrophobic attraction between the SF tails, a transition occurs inverting this structure to a spherical micelle with a neutral core of SF tails and a charged corona of SF heads with the PE molecule wrapped around. At intermediate hydrophobicity there is a competition between the two structures indicated by a non-monotonic dependence of the shape as function of the Coulomb strength, favoring the cylindrical shape for weak and the spherical micellar complex for strong interaction.

Sheath liquid interface for the coupling of normal‐phase liquid chromatography with electrospray mass spectrometry and its application to the analysis of neoflavonoids

A novel interface that allows normal-phase liquid chromatography to be coupled with electrospray ionization (ESI) is reported. A make-up solution of 60 mM ammonium acetate in methanol, infused at a 5 microl min(-1) flow-rate at the tip of the electrospray probe, provides a sheath liquid which is poorly miscible with the chromatographic effluent, but promotes efficient ionization of the targeted analytes. Protonated molecules generated in the ESI source were subjected to tandem mass spectrometric experiments in a triple-quadrupole mass spectrometer. The main fragmentation reactions were characterized for each analyte and specific mass spectral transitions were used to acquire chromatographic data in the multiple reaction monitoring detection mode. Results obtained during optimization of the sheath liquid composition and flow-rate suggest that the electrospray process was mainly under the control of the make-up solution, and that it forms an external charged layer around a neutral chromatographic mobile phase core. This sheath liquid interface was implemented for the analysis of some neoflavonoid compounds and its performance was evaluated. Limits of detection were established for calophillolide, inophyllum B, inophyllum P and inophyllum C at 100, 25, 15 and 100 ng ml(-1), respectively.

The static polarizability and first hyperpolarizability of the water trimer anion: Ab initio study

This work predicts the extraordinary hyperpolarizability of inorganic clusters: two water trimer anions. The first hyperpolarizabilities of (H2O-)(3) are considerable, beta(0)=1.715 x 10(7) a.u. for configuration A and beta(0)=1.129 x 10(7) a.u. for configuration B at MP2/d-aug-cc-pVDZ+x level. The first hyperpolarizabilities of (H2O-)(3) (configuration A) and related systems [(H2O)(3) and (H2O)(3)F-] are compared at the MP2/d-aug-cc-pVDZ+x level. These results are beta(0)=1.715 x 10(7) a.u. for (H2O-)(3), beta(0)=35 a.u. for (H2O)(3) [the neutral core of (H2O-)(3)], and beta(0)=46 a.u. for (H2O)(3)F-). Comparing the beta(0) values of related systems, we find that the dipole-bound excess electron is the key factor in the extraordinary first hyperpolarizability of (H2O-)(3) species. It will provide a future in the development of some materials with the excess electron (e.g., electrides) that exhibit large nonlinear optical response.

Formation and properties of positively charged colloids based on polyelectrolyte complexes of biopolymers.

Formation of colloids based on polyelectrolyte complexes (PECs) was mainly studied with synthetic polyelectrolytes. In this study, we describe the elaboration of positively charged PEC particles at a submicrometer level obtained by the complexation between two charged polysaccharides, chitosan as polycation and dextran sulfate (DS) as polyanion. The complexes were elaborated by dropwise addition of default amounts of DS to excess chitosan. Quasi-elastic light scattering was used to investigate in detail the influence of the characteristics of components (chain length, degree of acetylation) and parameters linked to the reaction of complexation (molar mixing ratio, ionic strength, concentration in polymer) on the sizes and polydispersity of colloids. Chain length of chitosan is the major parameter affecting the dimensions of the complexes, high molar mass chitosans leading to the largest particles. Variations of hydrodynamic diameters of PECs with the molar mass of chitosan are consistent with a mechanism of particle formation through the segregation of the neutral and then hydrophobic blocks of the polyelectrolyte complexed segments. Resulting particles display probably a structure constituted by a neutral core surrounded by a chitosan shell ensuring the colloidal stabilization. Such a structure was evidenced by measurements of electrophoretic mobilities revealing that the positive charge of particles was decreasing with pH, in relation with the neutralization of excess glucosamine hydrochloride moieties.

Preparation and photoelectron spectrum of the glycine molecular anion: assignment to a dipole-bound electron species with a high-dipole moment, non-zwitterionic form of the neutral core.

We report the gas-phase preparation of negatively charged glycine as well as the Gly(H(2)O)(1,2) (-) complexes by entrainment of the neutral precursor into an ionized supersonic expansion tuned to optimize the (H(2)O)(n) (-)Ar(m) clusters. The photoelectron spectrum of Gly(-) displays the signature of a dipole-bound species, with sufficient vibrational fine structure to characterize the core neutral as a higher energy, non-zwitterionic isomer of the amino acid.

An ab initio Prediction of the Extraordinary Static First Hyperpolarizability for the Electron‐Solvated Cluster (FH)2{e}(HF).

A theoretical prediction of the nonlinear optical (NLO) properties of the hydrogen fluoride trimer anion (FH)2{e}(HF) reveals that this electron-solvated cluster possesses exceptionally large static first hyperpolarizability. Using the d-aug-cc-pVDZ basis set supplemented with diffusive bond functions (BF), we obtained the mean static first hyperpolarizability (β0) for (FH)2{e}(HF) and its neutral core (HF)2{}(HF) at the CISD level of theory. The β0 is 8.1 × 106 au for (FH)2{e}(HF) and 5.1 au for (HF)2{}(HF). Obviously, the excess electron is the key factor in bringing to (FH)2{e}(HF) the significantly large NLO response. The other properties of (FH)2{e}(HF) are also much larger than those of its neutral core. The values of the static dipole moment, mean polarizability, and anisotropy of the polarizability are, respectively, μ = 1.5764 au, α0 = 654.67 au, and Δα = 224.71 au for the anion, and μ = 0.9351 au, α0 = 17.34 au, Δα = 5.40 au for the neutral core. In addition, the field dependences of the polariz...

Fenitrothion-induced structural and functional perturbations in the yolk lipoproteins of the shrimp Macrobrachium borellii.

Two lipovitellin (LV) forms containing the same apoproteins but differing in their lipid composition were isolated from Macrobrachium borelii eggs at early (LVe) and late (LVI) embryogenic stages and characterized. These two forms of LV, as well as liposomes prepared with lipids extracted from them, were used as simpler models to study the effect of the pesticide fenitrothion (FS) on their structures and functions. Rotational diffusion and fluorescence lifetime of two fluorescent probes [1,6-diphenyl-1,3,5-hexatriene (DPH) and 3-(p-(6-phenyl)-1,3,5-hexatrienal)phenylpropionic acid (DPH-PA)] were used to obtain information on structural changes induced by FS in the inner and outer regions of the LV, respectively. Comparison of the rotational behavior of these probes in native LV and liposomes (LP) from extracted LV lipids suggests that apoprotein-lipid interactions result in an ordered neutral lipid core. FS increased the lipid phase polarity of both LV and LP forms. The rotation of these probes in LP was not affected, suggesting a dependence of FS action on lipid-protein interactions. DPH-PA steady-state anisotropy showed that, unlike the LVe form, the LVI form was sensitive to extremely low FS concentrations. The ability of both LV to transfer palmitic acid to albumin was increased, but in a dissimilar manner, by the presence of FS. Such differences in the sensitivity of the LV at different steps of embryogenesis to FS influence the toxic action of this insecticide.

Optical observations of plasma formation and wire core expansion of Au, Ag, and Cu wires with 0–1 kA per wire

Explosions of Au, Ag, and Cu wires (1 cm long, 13–25 μm diameter, with/without insulating coatings) driven by a current pulser (4.5 kA peak, rise time 350 ns) were studied. Diagnostics included three channels of Schlieren imaging and two channels of shearing interferometry using the second harmonic of a Nd:YAG laser (λ=532 nm, 5 ns pulse width). The formation of a plasma shell around the neutral wire core was observed relatively late in time compared to the voltage collapse time. The corresponding plasma density was measured. From the refractive index of the wire core, some properties of the wire core material will also be discussed. The expansion rates of exploding wires were measured by interferometry and compared to the previously reported results. Two-wire experiments were also performed. The merging of the plasma at an increased plasma density was observed between two wires. The effects of the plasma shell on the wire expansion are discussed.

An ab Initio Prediction of the Extraordinary Static First Hyperpolarizability for the Electron-Solvated Cluster (FH)2{e}(HF)

A theoretical prediction of the nonlinear optical (NLO) properties of the hydrogen fluoride trimer anion (FH)2{e}(HF) reveals that this electron-solvated cluster possesses exceptionally large static first hyperpolarizability. Using the d-aug-cc-pVDZ basis set supplemented with diffusive bond functions (BF), we obtained the mean static first hyperpolarizability (β0) for (FH)2{e}(HF) and its neutral core (HF)2{}(HF) at the CISD level of theory. The β0 is 8.1 × 106 au for (FH)2{e}(HF) and 5.1 au for (HF)2{}(HF). Obviously, the excess electron is the key factor in bringing to (FH)2{e}(HF) the significantly large NLO response. The other properties of (FH)2{e}(HF) are also much larger than those of its neutral core. The values of the static dipole moment, mean polarizability, and anisotropy of the polarizability are, respectively, μ = 1.5764 au, α0 = 654.67 au, and Δα = 224.71 au for the anion, and μ = 0.9351 au, α0 = 17.34 au, Δα = 5.40 au for the neutral core. In addition, the field dependences of the polarizability and first hyperpolarizability are obtained at the MP2/d-aug-cc-pVDZ+BF level of theory. And the influence of the secondary interaction, H-bond-excess electron attracting, on the static first hyperpolarizability of (HF)2{e}(HF) is also explored.

Simulation of the Edge Plasma in Tokamaks

Edge plasma modelling is discussed with particular emphasis on the comparison of a fluid neutral model with a kinetic neutral model. By iterative inclusion of additional effects, the agreement between the two is improved. Of particular importance is the proper treatment of neutrals at the core boundary, the proper implementation of a neutral flux limit, and the modification of the ion heat boundary condition to include the neutral contribution. In the end, the agreement in the upstream profiles of electron and ion temperatures, and of electron and neutral core densities is very satisfactory. In addition, the effects of parallel ion and electron heat flux limiters, of transport ballooning to the low field side, and of drifts are investigated.

Structure of triglyceride-rich human low-density lipoproteins according to cryoelectron microscopy.

Low-density lipoprotein (LDL) particles from normolipidemic individuals contain a cholesteryl ester-rich core that undergoes a thermal transition from a liquid crystalline to an isotropic liquid phase between 20 and 35 degrees C. LDL from hypertriglyceridemic patients or prepared in vitro by the exchange of very low-density lipoprotein for LDL cholesteryl esters is triglyceride-rich, does not have a thermal transition above 0 degrees C, and exhibits impaired binding to the LDL receptor on normal human skin fibroblasts. Cryoelectron microscopy of LDL quick-frozen from 10 (core-frozen) and 40 degrees C (core-melted) revealed ellipsoidal particles with internal striations and round particles devoid of striations, respectively. Cryoelectron microscopy of triglyceride-rich LDL prepared in vitro revealed particles similar to the core-melted normolipidemic LDL, i.e., round particles without striations. These data suggest that the LDL core in the liquid crystalline phase is characterized by the appearance of striations, whereas LDL with a core that is an isotropic liquid lacks striations. It is suggested that freezing the LDL core into a liquid crystalline phase imposes structural constraints that force LDL from a sphere without partitions to an ellipsoid with partitions. We further suggest that the striation-defined lamellae are a structural feature of a liquid crystalline neutral lipid core that is a determinant of normal binding to the LDL receptor and that conversion of the neutral lipid core of LDL to the isotropic liquid phase via an increase in the temperature or via the addition of triglyceride partially ablates the receptor binding determinants on the LDL surface. This effect is likely achieved through changes in the conformation of apo-B-100. These data suggest that the physical state of the LDL core determines particle shape, surface structure, and metabolic fate.