Uptake and intra-inclusion accumulation of exogenous immunoglobulin by Chlamydia-infected cells

<p>Abstract</p> <p>Background</p> <p>Obligate intracellular pathogens belonging to the <it>Chlamydiaceae </it>family possess a number of mechanisms by which to manipulate the host cell and surrounding environment. Such capabilities include the inhibition of apoptosis, down-regulation of major histocompatability complex (MHC) and CD1/d gene expression, and the acquisition of host-synthesized nutrients. It is also documented that a limited number of host-derived macromolecules such as β-catenin and sphingomyelin accumulate within the inclusion.</p> <p>Results</p> <p>This report provides evidence that immunoglobulin, inherently present in the extracellular environment <it>in vivo </it>and <it>in vitro</it>, enters infected cells and accumulates within the chlamydial inclusion. Using epi-fluorescent and confocal microscopy, this selective uptake of Ig is shown to occur among human leukocytes <it>in vivo </it>as well as cells cultured <it>in vitro</it>. These findings were confirmed by detection of IgG in the lysate of infected cells by western blot hybridization. Sequestered antibodies appear to be present during the entire course of the chlamydial developmental cycle and are distributed throughout this compartment. IgG pre-labeled with fluorescein, when added to the supernatant of infected cell cultures, was also imported and readily visualized. Accumulation of these molecules within the inclusion and the failure of bovine serum albumin or F(ab')₂fragments to accumulate in a similar manner suggests the process of entry is specific for intact IgG molecules and not a result of pinocytosis, diffusion, or any other mass endocytic event.</p> <p>Conclusion</p> <p>Sequestration of a host cell-derived protein within the chlamydial inclusion, although unexpected, is not an unprecedented occurrence. However, selective accumulation of an exogenous host protein, such as extracellular IgG, has not been previously reported in connection with chlamydial infections. The selectivity of this process may indicate that this uptake plays an important role in pathogen physiology or virulence during infection and the phenomenon itself may give rise to novel diagnostic and therapeutic approaches.</p

Collective excitation of a Bose-Einstein condensate by modulation of the atomic scattering length

We excite the lowest-lying quadrupole mode of a Bose-Einstein condensate by modulating the atomic scattering length via a Feshbach resonance. Excitation occurs at various modulation frequencies, and resonances located at the natural quadrupole frequency of the condensate and at the first harmonic are observed. We also investigate the amplitude of the excited mode as a function of modulation depth. Numerical simulations based on a variational calculation agree with our experimental results and provide insight into the observed behavior.Comment: Submitted to PR

Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers.

BACKGROUND: Ticagrelor is an oral P2Y12 inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful. METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in healthy volunteers before and after 48 hours of ticagrelor pretreatment and again after the administration of PB2452 or placebo. Platelet function was assessed with the use of light transmission aggregometry, a point-of-care P2Y12 platelet-reactivity test, and a vasodilator-stimulated phosphoprotein assay. RESULTS: Of the 64 volunteers who underwent randomization, 48 were assigned to receive PB2452 and 16 to receive placebo. After 48 hours of ticagrelor pretreatment, platelet aggregation was suppressed by approximately 80%. PB2452 administered as an initial intravenous bolus followed by a prolonged infusion (8, 12, or 16 hours) was associated with a significantly greater increase in platelet function than placebo, as measured by multiple assays. Ticagrelor reversal occurred within 5 minutes after the initiation of PB2452 and was sustained for more than 20 hours (P\u3c0.001 after Bonferroni adjustment across all time points for all assays). There was no evidence of a rebound in platelet activity after drug cessation. Adverse events related to the trial drug were limited mainly to issues involving the infusion site. CONCLUSIONS: In healthy volunteers, the administration of PB2452, a specific reversal agent for ticagrelor, provided immediate and sustained reversal of the antiplatelet effects of ticagrelor, as measured by multiple assays. (Funded by PhaseBio Pharmaceuticals; ClinicalTrials.gov number, NCT03492385.)

Critical behavior of thermopower and conductivity at the metal-insulator transition in high-mobility Si-MOSFET's

This letter reports thermopower and conductivity measurements through the metal-insulator transition for 2-dimensional electron gases in high mobility Si-MOSFET's. At low temperatures both thermopower and conductivity show critical behavior as a function of electron density which is very similar to that expected for an Anderson transition. In particular, when approaching the critical density from the metallic side the diffusion thermopower appears to diverge and the conductivity vanishes. On the insulating side the thermopower shows an upturn with decreasing temperature.Comment: 4 pages with 3 figure

Bounds on the force between black holes

We treat the problem of N interacting, axisymmetric black holes and obtain two relations among physical parameters of the system including the force between the black holes. The first relation involves the total mass, the angular momenta, the distances and the forces between the black holes. The second one relates the angular momentum and area of each black hole with the forces acting on it.Comment: 13 pages, no figure

Three-body recombination rates near a Feshbach resonance within a two-channel contact interaction model

We calculate the three-body recombination rate into a shallow dimer in a gas of cold bosonic atoms near a Feshbach resonance using a two-channel contact interaction model. The two-channel model naturally describes the variation of the scattering length through the Feshbach resonance and has a finite effective range. We confront the theory with the available experimental data and show that the two-channel model is able to quantitatively describe the existing data. The finite effective range leads to a reduction of the scaling factor between the recombination minima from the universal value of 22.7. The reduction is larger for larger effective ranges or, correspondingly, for narrower Feshbach resonances.Comment: 9 pages, 7 figure

Dielectrophoresis-Driven Spreading of Immersed Liquid Droplets

In recent years electrowetting-on-dielectric (EWOD) has become an effective tool to control partial wetting. EWOD uses the liquid−solid interface as part of a capacitive structure that allows capacitive and interfacial energies to adjust by changes in wetting when the liquid−solid interface is charged due to an applied voltage. An important aspect of EWOD has been its applications in micro fluidics in chemistry and biology and in optical devices and displays in physics and engineering. Many of these rely on the use of a liquid droplet immersed in a second liquid due to the need either for neutral buoyancy to overcome gravity and shield against impact shocks or to encapsulate the droplet for other reasons, such as in microfluidic-based DNA analyses. Recently, it has been shown that nonwetting oleophobic surfaces can be forcibly wetted by nonconducting oils using nonuniform electric fields and an interface-localized form of liquid dielectrophoresis (dielectrowetting). Here we show that this effect can be used to create films of oil immersed in a second immiscible fluid of lower permittivity. We predict that the square of the thickness of the film should obey a simple law dependent on the square of the applied voltage and with strength dependent on the ratio of difference in permittivity to the liquid-fluid interfacial tension, Δε/γLF. This relationship is experimentally confirmed for 11 liquid−air and liquid−liquid combinations with Δε/γLF having a span of more than two orders of magnitude. We therefore provide fundamental understanding of dielectrowetting for liquid-in-liquid systems and also open up a new method to determine liquid−liquid interfacial tensions

Modulation of LISA free-fall orbits due to the Earth-Moon system

We calculate the effect of the Earth-Moon (EM) system on the free-fall motion of LISA test masses. We show that the periodic gravitational pulling of the EM system induces a resonance with fundamental frequency 1 yr^-1 and a series of periodic perturbations with frequencies equal to integer harmonics of the synodic month (9.92 10^-7 Hz). We then evaluate the effects of these perturbations (up to the 6th harmonics) on the relative motions between each test masses couple, finding that they range between 3mm and 10pm for the 2nd and 6th harmonic, respectively. If we take the LISA sensitivity curve, as extrapolated down to 10^-6 Hz, we obtain that a few harmonics of the EM system can be detected in the Doppler data collected by the LISA space mission. This suggests that the EM system gravitational near field could provide an absolute calibration for the LISA sensitivity at very low frequencies.Comment: 15 pages, 5 figure