Inhibition Of The Ysc Type III Secretion System Of Yersinia Pestis By Compound D And Interaction Of Type III Secretion System Needle Proteins With Host Receptors

The type III secretion system of gram-negative bacterial pathogens is a major virulence factor and functions to modulate host immune responses. Immune modulation occurs in many ways, including direct injection of effector proteins or indirect methods such as the detection of bacterial components by host immune receptors. Knowledge of these immune modulations allows for development of treatment options in an ever-increasing antibiotic-resistance climate. The studies presented here explore both areas of immune modulation. We identify Compound D as a potent inhibitor of the type III secretion system of Yersinia pestis. Through evaluation of effector secretion by bacteria grown in the presence of Compound D, we establish that inhibition of secretion occurs through translocon protein YopD and is also affected by LcrQ and YopD\u27s chaperone, LcrH. Type III Secretion inhibition by Compound D also requires a secretion active state of the type III secretion system as determined by analysis of strains that constitutively secrete effectors. The other study focuses on host recognition of bacterial proteins, specifically the needle protein of type III secretion systems. Via utilization of cells that secrete a measurable signal protein when NF-κB or AP-1 is activated, we show that needle proteins from Yersinia pestis, Salmonella enterica serovar Typhimurium, and Shigella flexneri are capable of activating cells through Toll-like receptors 2 and 4. This interaction appears to be modulated by the N-terminus, that is reported to reside on the outside of the fully formed needle structure, exposed to host receptors. Activation of NF-κB/AP-1 correlates with production of TNF-α in response to needle proteins

Pioneer 10 and Voyager observations of the interstellar medium in scattered emission of the He584 A and H Lya 1216 A lines

The combination of Pioneer photometric and Voyager spectrometric observations of EUV interstellar-interplanetary emissions in the region beyond 5 A was applied to a determination of atomic hydrogen and helium densities. These density estimates obtained from direct measurement of scattered radiation depend on absolute calibration of the instruments in the same way as other earlier determinations based on the same method. However, the spacecraft data were combined with daily full sun averages of the H Lyman 1216 A line obtained by the Solar Mesospheric Explorer satellite to obtain a measure of atomic hydrogen density independent of instrument absolute calibration. The method depends on observations of long and short term temporal variability of the solar line over a one year period, and the fact that the ISM is optically thick. The density estimates from preliminary work on these observations are H = 0.12 cu cm and H = .016 cu cm, giving a density ratio close to the cosmic abundance value in contrast to some earlier results indicating a depletion of atomic hydrogen. Estimates were obtained of galactic background emissions in the signals of both spacecraft

TSG-6 and calcium ions are essential for the coupling of inter-alpha-trypsin inhibitor to hyaluronan in human synovial fluid

AbstractObjective: To investigate the role of tumor necrosis factor stimulated gene 6 (TSG-6) and metal ions in the coupling of inter-α-trypsin inhibitor (ITI) to hyaluronan in human synovial fluid.Design: The concentration of ITI heavy chains bound to hyaluronan was determined by a two-step electrophoretic technique. Synovial fluid, TSG-6 depleted synovial fluid and metal chelated synovial fluid were tested for their ability to support the coupling of ITI heavy chains to hyaluronan.Results: When synovial fluid was mixed with an ITI-source (serum or purified ITI), coupling of ITI heavy chains to hyaluronan took place. TSG-6 immunodepleated synovial fluid lost the coupling activity, but addition of recombinant TSG-6 restored the activity. EDTA inhibited the coupling activity, but combinations of the metal-ion chelators Mg-EGTA and Ca-EGTA demonstrated, that Ca++is essential for the coupling of ITI heavy chains to hyaluronan.Conclusions: Tumor necrosis factor stimulated gene 6 (TSG-6) and calcium ions are both essential for the coupling of inter-α-trypsin inhibitor to hyaluronan in human synovial fluid

TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

Observations of the magnetic field and plasma flow in Jupiter's magnetosheath

Large scale (many minutes to 10 hours) magnetic field structures consisting predominantly of nearly north-south field direction were discovered in Jupiter's magnetosheath from the data of Voyagers 1 and 2 and Pioneer 10 during their outbound encounter trajectories. The Voyager 2 data, and that of Voyager 1 to a lesser extent, show evidence of a quasi-period of 10 hours (and occasionally 5 hours) for these structures. The north-south components of the field and plasma velocity were strongly correlated in the outbound magnetosheath as observed by Voyagers 1 and 2, and the components orthogonal to the north-south direction showed weak correlations. For both Voyager encounters the sense (positive and negative) of the north-south correlations were directly related to the direction of the ecliptic plane component of the interplanetary magnetic field using the field and plasma measurements of the non-encountering spacecraft

Accurate Microwave Control and Real-Time Diagnostics of Neutral Atom Qubits

We demonstrate accurate single-qubit control in an ensemble of atomic qubits trapped in an optical lattice. The qubits are driven with microwave radiation, and their dynamics tracked by optical probe polarimetry. Real-time diagnostics is crucial to minimize systematic errors and optimize the performance of single-qubit gates, leading to fidelities of 0.99 for single-qubit pi rotations. We show that increased robustness to large, deliberately introduced errors can be achieved through the use of composite rotations. However, during normal operation the combination of very small intrinsic errors and additional decoherence during the longer pulse sequences precludes any significant performance gain in our current experiment.Comment: 9 pages, 7 figure

Manipulation of Single Neutral Atoms in Optical Lattices

We analyze a scheme to manipulate quantum states of neutral atoms at individual sites of optical lattices using focused laser beams. Spatial distributions of focused laser intensities induce position-dependent energy shifts of hyperfine states, which, combined with microwave radiation, allow selective manipulation of quantum states of individual target atoms. We show that various errors in the manipulation process are suppressed below $10^{-4}$ with properly chosen microwave pulse sequences and laser parameters. A similar idea is also applied to measure quantum states of single atoms in optical lattices.Comment: 5 pages, 3 figure

Optical Lattice Polarization Effects on Hyperpolarizability of Atomic Clock Transitions

The light-induced frequency shift due to the hyperpolarizability (i.e. terms of second-order in intensity) is studied for a forbidden optical transition, $J$=0$\to$$J$=0. A simple universal dependence on the field ellipticity is obtained. This result allows minimization of the second-order light shift with respect to the field polarization for optical lattices operating at a magic wavelength (at which the first-order shift vanishes). We show the possibility for the existence of a magic elliptical polarization, for which the second-order frequency shift vanishes. The optimal polarization of the lattice field can be either linear, circular or magic elliptical. The obtained results could improve the accuracy of lattice-based atomic clocks.Comment: 4 pages, RevTeX4, 2 eps fig