Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition

AbstractMabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell

Limited contributions of plant pathogens to density‐dependent seedling mortality of mast fruiting Bornean trees

Fungal pathogens are implicated in driving tropical plant diversity by facilitating strong, negative density‐dependent mortality of conspecific seedlings (C‐NDD). Assessment of the role of fungal pathogens in mediating coexistence derives from relatively few tree species and predominantly the Neotropics, limiting our understanding of their role in maintaining hyper‐diversity in many tropical forests. A key question is whether fungal pathogen‐mediated C‐NDD seedling mortality is ubiquitous across diverse plant communities. Using a manipulative shadehouse experiment, we tested the role of fungal pathogens in mediating C‐NDD seedling mortality of eight mast fruiting Bornean trees, typical of the species‐rich forests of South East Asia. We demonstrate species‐specific responses of seedlings to fungicide and density treatments, generating weak negative density‐dependent mortality. Overall seedling mortality was low and likely insufficient to promote overall community diversity. Although conducted in the same way as previous studies, we find little evidence that fungal pathogens play a substantial role in determining patterns of seedling mortality in a SE Asian mast fruiting forest, questioning our understanding of how Janzen‐Connell mechanisms structure the plant communities of this globally important forest type

Structural identifiability of surface binding reactions involving heterogeneous analyte : application to surface plasmon resonance experiments

Binding affinities are useful measures of target interaction and have an important role in understanding biochemical reactions that involve binding mechanisms. Surface plasmon resonance (SPR) provides convenient real-time measurement of the reaction that enables subsequent estimation of the reaction constants necessary to determine binding affinity. Three models are considered for application to SPR experiments—the well mixed Langmuir model and two models that represent the binding reaction in the presence of transport effects. One of these models, the effective rate constant approximation, can be derived from the other by applying a quasi-steady state assumption. Uniqueness of the reaction constants with respect to SPR measurements is considered via a structural identifiability analysis. It is shown that the models are structurally unidentifiable unless the sample concentration is known. The models are also considered for analytes with heterogeneity in the binding kinetics. This heterogeneity further confounds the identifiability of key parameters necessary for reliable estimation of the binding affinit

On the chirality of quark modes

A model for the QCD vacuum based on a domainlike structured background gluon field with definite duality attributed to the domains has been shown elsewhere to give confinement of static quarks, a reasonable value for the topological susceptibility and indications that chiral symmetry is spontaneously broken. In this paper we study in detail the eigenvalue problem for the Dirac operator in such a gluon mean field. A study of the local chirality parameter shows that the lowest nonzero eigenmodes possess a definite mean chirality correlated with the duality of a given domain. A probability distribution of the local chirality qualitatively reproduces histograms seen in lattice simulations.Comment: RevTeX4, 5 figures, 14 page

A particle-number-conserving Bogoliubov method which demonstrates the validity of the time-dependent Gross-Pitaevskii equation for a highly condensed Bose gas

The Bogoliubov method for the excitation spectrum of a Bose-condensed gas is generalized to apply to a gas with an exact large number $N$ of particles. This generalization yields a description of the Schr\"odinger picture field operators as the product of an annihilation operator $A$ for the total number of particles and the sum of a ``condensate wavefunction'' $\xi(x)$ and a phonon field operator $\chi(x)$ in the form $\psi(x) \approx A\{\xi(x) + \chi(x)/\sqrt{N}\}$ when the field operator acts on the N particle subspace. It is then possible to expand the Hamiltonian in decreasing powers of $\sqrt{N}$, an thus obtain solutions for eigenvalues and eigenstates as an asymptotic expansion of the same kind. It is also possible to compute all matrix elements of field operators between states of different N.Comment: RevTeX, 11 page

Boson induced s-wave pairing in dilute boson-fermion mixtures

We show that in dilute boson-fermion mixtures with fermions in two internal states, even when the bare fermion-fermion interaction is repulsive, the exchange of density fluctuations of the Bose condensate may lead to an effective fermion-fermion attraction, and thus to a Cooper instability in the s-wave channel. We give an analytical method to derive the associated $T_c$ in the limit where the phonon branch of the Bogoliubov excitation spectrum of the bosons is important. We find a $T_c$ of the same order as for a pure Fermi gas with bare attraction.Comment: 12 pages, no figure

Acceptor state anchoring in gallium nitride

The dual nature of the magnesium acceptor in gallium nitride results in dynamic defect complexes. Europium spectator ions reveal switching between two spectrally unique metastable centres, each corresponding to a particular acceptor state. By ion co-implantation of europium and oxygen into GaN(Mg), we produce, in addition, an anchored state system. In doing so we create an abundance of previously unidentified stable centres which we denote as "Eu0(Ox)". We introduce a microscopic model for these centres with oxygen substituting for nitrogen in the bridging site

The societal costs of femoral neck fracture patients treated with internal fixation

__Abstract__ The study rationale was to provide a detailed overview of the costs for femoral neck fracture treatment with internal fixation in the Netherlands. Mean total costs per patient at 2-years follow-up were €19,425. Costs were higher for older, less healthy patients. Results are comparable to internationally published costs. Introduction The aim of this study was to provide a detailed overview of the cost and healthcare consumptio

Determinants of species richness in the Park Grass experiment

The Park Grass Experiment at Rothamsted in southeast England was started in 1856, making it the longest-running experiment in plant ecology anywhere in the world. Experimental inputs include a range of fertilizers (nitrogen, phosphorus, potassium, and organic manures) applied annually, with lime applied occasionally, and these have led to an increase in biomass and, where nitrogen was applied in the form of ammonium sulfate, to substantial decreases in soil pH. The number of species per plot varies from three to 44 per 200 m2, affording a unique opportunity to study the determinants of plant species richness and to estimate the effect sizes attributable to different factors. The response of species richness to biomass depends on the amount and type of nitrogen applied; richness declined monotonically with increasing biomass on plots receiving no nitrogen or receiving nitrogen in the form of sodium nitrate, but there was no relationship between species richness and biomass on plots acidified by ammonium sulfate application. The response to lime also depended on the type of nitrogen applied; there was no relationship between lime treatment and species richness, except in plots receiving nitrogen in the form of ammonium sulfate, where species richness increased sharply with increasing soil pH. The addition of phosphorus reduced species richness, and application of potassium along with phosphorus reduced species richness further, but the biggest negative effects were when nitrogen and phosphorus were applied together. The analysis demonstrates how multiple factors contribute to the observed diversity patterns and how environmental regulation of species pools can operate at the same spatial and temporal scale as biomass effects