Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon.

Clinical persistence of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) is a major public health concern. In vitro persistence is known to develop through interferon gamma (IFN-γ) induction of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, an essential amino acid for Ct replication. The organism can recover from persistence by synthesizing tryptophan from indole, a substrate for the enzyme tryptophan synthase. The majority of Ct strains, except for reference strain B/TW-5/OT, contain an operon comprised of α and β subunits that encode TrpA and TrpB, respectively, and form a functional αββα tetramer. However, trpA mutations in ocular Ct strains, which are responsible for the blinding eye disease known as trachoma, abrogate tryptophan synthesis from indole. We examined serial urogenital samples from a woman who had recurrent Ct infections over 4 years despite antibiotic treatment. The Ct isolates from each infection episode were genome sequenced and analyzed for phenotypic, structural, and functional characteristics. All isolates contained identical mutations in trpA and developed aberrant bodies within intracellular inclusions, visualized by transmission electron microscopy, even when supplemented with indole following IFN-γ treatment. Each isolate displayed an altered αββα structure, could not synthesize tryptophan from indole, and had significantly lower trpBA expression but higher intracellular tryptophan levels compared with those of reference Ct strain F/IC-Cal3. Our data indicate that emergent mutations in the tryptophan operon, which were previously thought to be restricted only to ocular Ct strains, likely resulted in in vivo persistence in the described patient and represents a novel host-pathogen adaptive strategy for survival.IMPORTANCE Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium with more than 131 million cases occurring annually worldwide. Ct infections are often asymptomatic, persisting for many years despite treatment. In vitro recovery from persistence occurs when indole is utilized by the organism's tryptophan synthase to synthesize tryptophan, an essential amino acid for replication. Ocular but not urogenital Ct strains contain mutations in the synthase that abrogate tryptophan synthesis. Here, we discovered that the genomes of serial isolates from a woman with recurrent, treated Ct STIs over many years were identical with a novel synthase mutation. This likely allowed long-term in vivo persistence where active infection resumed only when tryptophan became available. Our findings indicate an emerging adaptive host-pathogen evolutionary strategy for survival in the urogenital tract that will prompt the field to further explore chlamydial persistence, evaluate the genetics of mutant Ct strains and fitness within the host, and their implications for disease pathogenesis

Covariant Helicity-Coupling Amplitudes: A New Formulation

We have worked out covariant amplitudes for any two-body decay of a resonance with an arbitrary non-zero mass, which involves arbitrary integer spins in the initial and the final states. One key new ingredient for this work is the application of the total intrinsic spin operator $\vec S$ which is given directly in terms of the generators of the Poincar\'e group. Using the results of this study, we show how to explore the Lorentz factors which appear naturally, if the momentum-space wave functions are used to form the covariant decay amplitudes. We have devised a method of constructing our covariant decay amplitudes, such that they lead to the Zemach amplitudes when the Lorentz factors are set one

Adaptations of Pseudomonas aeruginosa to the Cystic Fibrosis Lung Environment Can Include Deregulation of zwf, Encoding Glucose-6-Phosphate Dehydrogenase

Cystic fibrosis (CF) patients are highly susceptible to chronic pulmonary disease caused by mucoid Pseudomonas aeruginosa strains that overproduce the exopolysaccharide alginate. We showed here that a mutation in zwf, encoding glucose-6-phosphate dehydrogenase (G6PDH), leads to a 90% reduction in alginate production in the mucoid, CF isolate, P. aeruginosa FRD1. The main regulator of alginate, sigma-22 encoded by algT (algU), plays a small but demonstrable role in the induction of zwf expression in P. aeruginosa. However, G6PDH activity and zwf expression were higher in FRD1 strains than in PAO1 strains. In PAO1, zwf expression and G6PDH activity are known to be subject to catabolite repression by succinate. In contrast, FRD1 zwf expression and G6PDH activity were shown to be refractory to such catabolite repression. This was apparently not due to a defect in the catabolite repression control (Crc) protein. Such relaxed control of zwf was found to be common among several examined CF isolates but was not seen in other strains of clinical and environmental origin. Two sets of clonal isolates from individual CF patient indicated that the resident P. aeruginosa strain underwent an adaptive change that deregulated zwf expression. We hypothesized that high-level, unregulated G6PDH activity provided a survival advantage to P. aeruginosa within the lung environment. Interestingly, zwf expression in P. aeruginosa was shown to be required for its resistance to human sputum. This study illustrates that adaptation to the CF pulmonary environment by P. aeruginosa can include altered regulation of basic metabolic activities, including carbon catabolism. Originally published Journal of Bacteriology, Vol. 187, No. 22, Nov 200

Observation and interpretation of motional sideband asymmetry in a quantum electro-mechanical device

Quantum electro-mechanical systems offer a unique opportunity to probe quantum noise properties in macroscopic devices, properties which ultimately stem from the Heisenberg Uncertainty Principle. A simple example of this is expected to occur in a microwave parametric transducer, where mechanical motion generates motional sidebands corresponding to the up and down frequency-conversion of microwave photons. Due to quantum vacuum noise, the rates of these processes are expected to be unequal. We measure this fundamental imbalance in a microwave transducer coupled to a radio-frequency mechanical mode, cooled near the ground state of motion. We also discuss the subtle origin of this imbalance: depending on the measurement scheme, the imbalance is most naturally attributed to the quantum fluctuations of either the mechanical mode or of the electromagnetic field

Triplet Production by Linearly Polarized Photons

The process of electron-positron pair production by linearly polarized photons is used as a polarimeter to perform mobile measurement of linear photon polarization. In the limit of high photon energies, omega, the distributions of the recoil-electron momentum and azimuthal angle do not depend on the photon energy in the laboratory frame. We calculate the power corrections of order m/omega to the above distributions and estimate the deviation from the asymptotic result for various values of omega.Comment: LaTeX2e, 13 pages, 5 figure files (eps), submitted to Phys. Rev.

Quantum squeezing of motion in a mechanical resonator

As a result of the quantum, wave-like nature of the physical world, a harmonic oscillator can never be completely at rest. Even in the quantum ground state, its position will always have fluctuations, called the zero-point motion. Although the zero-point fluctuations are unavoidable, they can be manipulated. In this work, using microwave frequency radiation pressure, we both prepare a micron-scale mechanical system in a state near the quantum ground state and then manipulate its thermal fluctuations to produce a stationary, quadrature-squeezed state. We deduce that the variance of one motional quadrature is 0.80 times the zero-point level, or 1 dB of sub-zero-point squeezing. This work is relevant to the quantum engineering of states of matter at large length scales, the study of decoherence of large quantum systems, and for the realization of ultra-sensitive sensing of force and motion

Fracture toughness and crack-resistance curve behavior in metallic glass-matrix composites

Nonlinear-elastic fracture mechanics methods are used to assess the fracture toughness of bulk metallic glass (BMG) composites; results are compared with similar measurements for other monolithic and composite BMG alloys. Mechanistically, plastic shielding gives rise to characteristic resistance-curve behavior where the fracture resistance increases with crack extension. Specifically, confinement of damage by second-phase dendrites is shown to result in enhancement of the toughness by nearly an order of magnitude relative to unreinforced glass

Mechanically Detecting and Avoiding the Quantum Fluctuations of a Microwave Field

During the theoretical investigation of the ultimate sensitivity of gravitational wave detectors through the 1970's and '80's, it was debated whether quantum fluctuations of the light field used for detection, also known as photon shot noise, would ultimately produce a force noise which would disturb the detector and limit the sensitivity. Carlton Caves famously answered this question with "They do." With this understanding came ideas how to avoid this limitation by giving up complete knowledge of the detector's motion. In these back-action evading (BAE) or quantum non-demolition (QND) schemes, one manipulates the required quantum measurement back-action by placing it into a component of the motion which is unobserved and dynamically isolated. Using a superconducting, electro-mechanical device, we realize a sensitive measurement of a single motional quadrature with imprecision below the zero-point fluctuations of motion, detect both the classical and quantum measurement back-action, and demonstrate BAE avoiding the quantum back-action from the microwave photons by 9 dB. Further improvements of these techniques are expected to provide a practical route to manipulate and prepare a squeezed state of motion with mechanical fluctuations below the quantum zero-point level, which is of interest both fundamentally and for the detection of very weak forces

Exploring the Oxygen Order in Hg-1223 and Hg-1201 by 199Hg MAS NMR

We demonstrate the use of a high-resolution solid-state fast (45 kHz) magic angle spinning (MAS) NMR for mapping the oxygen distribution in Hg-based cuprate superconductors. We identify observed three peaks in 199Hg spectrum as belonging to the different chemical environments in the HgO? layer with no oxygen neighbors, single oxygen neighbor, and two oxygen neighbors. We discuss observed differences between Hg-1201 and Hg-1223 materials.Comment: 4 pages, 2 figures included. Submitted to NATO Advanced Research Workshop Proceedings (Miami January 2004