Toxoplasma gondii major surface antigen (SAG1): in vitro analysis of host cell binding

Previous studies have indicated that SAG1, the major surface molecule of the protozoan parasite Toxoplasma gondii, is an important attachment ligand for the host cell. However, the research data that supports this claim comes largely from studies investigating tachyzoite binding, and not SAG1 binding per se. In this study we successfully developed an in vitro attachment assay to directly evaluate the mechanism of SAG1-host cell binding. Competition experiments were then performed using SAG1 that had been pre-treated with the neoglycoprotein BSA-glucosamide or with antibody. Soluble BSA-glucosamide blocked SAG1 attachment to MDBK cells in a dose-dependent manner, implying that SAG1 binding is mediated, in part, via attachment to host cell surface glucosamine. Interestingly, pre-incubation of SAG1 in polyclonal sera from chronically infected mice failed to block binding. This challenges the assumption that anti-SAG1 antibodies block parasite attachment through the masking of SAG1 host cell binding domains. Taken together, this evidence presents new strategies for understanding SAG1-mediated attachment

A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep

Chronic gonadotropin-releasing hormone agonist (GnRHa) administration is used where suppression of hypothalamic-pituitary-gonadal axis activity is beneficial, such as steroid-dependent cancers, early onset gender dysphoria, central precocious puberty and as a reversible contraceptive in veterinary medicine. GnRH receptors, however, are expressed outside the reproductive axis, e.g. brain areas such as the hippocampus which is crucial for learning and memory processes. Previous work, using an ovine model, has demonstrated that long-term spatial memory is reduced in adult rams (45 weeks of age), following peripubertal blockade of GnRH signaling (GnRHa: goserelin acetate), and this was independent of the associated loss of gonadal steroid signaling. The current study investigated whether this effect is reversed after discontinuation of GnRHa-treatment. The results demonstrate that peripubertal GnRHa-treatment suppressed reproductive function in rams, which was restored after cessation of GnRHa-treatment at 44 weeks of age, as indicated by similar testes size (relative to body weight) in both GnRHa-Recovery and Control rams at 81 weeks of age. Rams in which GnRHa-treatment was discontinued (GnRHa-Recovery) had comparable spatial maze traverse times to Controls, during spatial orientation and learning assessments at 85 and 99 weeks of age. Former GnRHa-treatment altered how quickly the rams progressed beyond a specific point in the spatial maze at 83 and 99 weeks of age, and the direction of this effect depended on gonadal steroid exposure, i.e. GnRHa-Recovery rams progressed quicker during breeding season and slower during non-breeding season, compared to Controls. The long-term spatial memory performance of GnRHa-Recovery rams remained reduced (P < 0.05, 1.5-fold slower) after discontinuation of GnRHa, compared to Controls. This result suggests that the time at which puberty normally occurs may represent a critical period of hippocampal plasticity. Perturbing normal hippocampal formation in this peripubertal period may also have long lasting effects on other brain areas and aspects of cognitive function

Electronic dynamic Hubbard model: exact diagonalization study

A model to describe electronic correlations in energy bands is considered. The model is a generalization of the conventional Hubbard model that allows for the fact that the wavefunction for two electrons occupying the same Wannier orbital is different from the product of single electron wavefunctions. We diagonalize the Hamiltonian exactly on a four-site cluster and study its properties as function of band filling. The quasiparticle weight is found to decrease and the quasiparticle effective mass to increase as the electronic band filling increases, and spectral weight in one- and two-particle spectral functions is transfered from low to high frequencies as the band filling increases. Quasiparticles at the Fermi energy are found to be more 'dressed' when the Fermi level is in the upper half of the band (hole carriers) than when it is in the lower half of the band (electron carriers). The effective interaction between carriers is found to be strongly dependent on band filling becoming less repulsive as the band filling increases, and attractive near the top of the band in certain parameter ranges. The effective interaction is most attractive when the single hole carriers are most heavily dressed, and in the parameter regime where the effective interaction is attractive, hole carriers are found to 'undress', hence become more like electrons, when they pair. It is proposed that these are generic properties of electronic energy bands in solids that reflect a fundamental electron-hole asymmetry of condensed matter. The relation of these results to the understanding of superconductivity in solids is discussed.Comment: Small changes following referee's comment

Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep

Chronic gonadotropin-releasing hormone agonist (GnRHa) is used therapeutically to block activity within the reproductive axis through down-regulation of GnRH receptors within the pituitary gland. GnRH receptors are also expressed in non-reproductive tissues, including areas of the brain such as the hippocampus and amygdala. The impact of long-term GnRHa-treatment on hippocampus-dependent cognitive functions, such as spatial orientation, learning and memory, is not well studied, particularly when treatment encompasses a critical window of development such as puberty. The current study used an ovine model to assess spatial maze performance and memory of rams that were untreated (Controls), had both GnRH and testosterone signaling blocked (GnRHa-treated), or specifically had GnRH signaling blocked (GnRHa-treated with testosterone replacement) during the peripubertal period (8, 27 and 41 weeks of age). The results demonstrate that emotional reactivity during spatial tasks was compromised by the blockade of gonadal steroid signaling, as seen by the restorative effects of testosterone replacement, while traverse times remained unchanged during assessment of spatial orientation and learning. The blockade of GnRH signaling alone was associated with impaired retention of long-term spatial memory and this effect was not restored with the replacement of testosterone signaling. These results indicate that GnRH signaling is involved in the retention and recollection of spatial information, potentially via alterations to spatial reference memory, and that therapeutic medical treatments using chronic GnRHa may have effects on this aspect of cognitive function

Abundance and evolution of galaxy clusters in cosmological models with massive neutrino

The time evolution of the number density of galaxy clusters and their mass and temperature functions are used to constrain cosmological parameters in the spatially flat dark matter models containing a fraction of hot particles (massive neutrino) additional to cold and baryonic matter. We test the modified MDM models with cosmic gravitational waves and show that they neither pass the cluster evolution test nor reproduce the observed height of the first acoustic peak in $\Delta T/T$ spectrum, and therefore should be ruled out. The models with a non-zero cosmological constant are in better agreement with observations. We estimate the free cosmological parameters in $\Lambda$MDM with a negligible abundance of gravitational waves, and find that within the parameter ranges $h\in (0.6, 0.7)$, $n\in (0.9, 1.1)$, (i) the value of $\Omega_\Lambda$ is strongly affected by a small fraction of hot dark matter, $f_\nu\equiv\Omega_\nu /\Omega_m\in (0, 0.2)$: $0.45 <\Omega_\Lambda <0.7$ ($1\sigma$ CL), and (ii) the redshift evolution of galaxy clusters alone reveals the following explicit correlation between $\Omega_\Lambda$ and $f_\nu$: $\Omega_\Lambda +0.5f_\nu =0.65\pm 0.1$. The present accuracy of observational data allows only to bound the fraction of hot matter, $f_\nu\in (0, 0.2)$ (the number of massive neutrino species remains undelimited, $N_\nu =1, 2, 3$).Comment: 9 pages, 7 figures, submitted in A&

Lines pinning lines

A line g is a transversal to a family F of convex polytopes in 3-dimensional space if it intersects every member of F. If, in addition, g is an isolated point of the space of line transversals to F, we say that F is a pinning of g. We show that any minimal pinning of a line by convex polytopes such that no face of a polytope is coplanar with the line has size at most eight. If, in addition, the polytopes are disjoint, then it has size at most six. We completely characterize configurations of disjoint polytopes that form minimal pinnings of a line.Comment: 27 pages, 10 figure

Simulations of neutron background in a time projection chamber relevant to dark matter searches

Presented here are results of simulations of neutron background performed for a time projection chamber acting as a particle dark matter detector in an underground laboratory. The investigated background includes neutrons from rock and detector components, generated via spontaneous fission and (alpha, n) reactions, as well as those due to cosmic-ray muons. Neutrons were propagated to the sensitive volume of the detector and the nuclear recoil spectra were calculated. Methods of neutron background suppression were also examined and limitations to the sensitivity of a gaseous dark matter detector are discussed. Results indicate that neutrons should not limit sensitivity to WIMP-nucleon interactions down to a level of (1 - 3) x 10^{-8} pb in a 10 kg detector.Comment: 27 pages (total, including 3 tables and 11 figures). Accepted for publication in Nuclear Instruments and Methods in Physics Research - Section

Adaiabtic theorems and reversible isothermal processes

Isothermal processes of a finitely extended, driven quantum system in contact with an infinite heat bath are studied from the point of view of quantum statistical mechanics. Notions like heat flux, work and entropy are defined for trajectories of states close to, but distinct from states of joint thermal equilibrium. A theorem characterizing reversible isothermal processes as quasi-static processes (''isothermal theorem'') is described. Corollaries concerning the changes of entropy and free energy in reversible isothermal processes and on the 0th law of thermodynamics are outlined

Neutron background in large-scale xenon detectors for dark matter searches

Simulations of the neutron background for future large-scale particle dark matter detectors are presented. Neutrons were generated in rock and detector elements via spontaneous fission and (alpha,n) reactions, and by cosmic-ray muons. The simulation techniques and results are discussed in the context of the expected sensitivity of a generic liquid xenon dark matter detector. Methods of neutron background suppression are investigated. A sensitivity of $10^{-9}-10^{-10}$ pb to WIMP-nucleon interactions can be achieved by a tonne-scale detector.Comment: 35 pages, 13 figures, 2 tables, accepted for publication in Astroparticle Physic