SpxA1 and SpxA2 act coordinately to fine-tune stress responses and virulence in Streptococcus pyogenes

SpxA is a unique transcriptional regulator highly conserved among members of the phylum Firmicutes that binds RNA polymerase and can act as an antiactivator. Why some Firmicutes members have two highly similar SpxA paralogs is not understood. Here, we show that the SpxA paralogs of the pathogen Streptococcus pyogenes, SpxA1 and SpxA2, act coordinately to regulate virulence by fine-tuning toxin expression and stress resistance. Construction and analysis of mutants revealed that SpxA1− mutants were defective for growth under aerobic conditions, while SpxA2− mutants had severely attenuated responses to multiple stresses, including thermal and oxidative stresses. SpxA1− mutants had enhanced resistance to the cationic antimicrobial molecule polymyxin B, while SpxA2− mutants were more sensitive. In a murine model of soft tissue infection, a SpxA1− mutant was highly attenuated. In contrast, the highly stress-sensitive SpxA2− mutant was hypervirulent, exhibiting more extensive tissue damage and a greater bacterial burden than the wild-type strain. SpxA1− attenuation was associated with reduced expression of several toxins, including the SpeB cysteine protease. In contrast, SpxA2− hypervirulence correlated with toxin overexpression and could be suppressed to wild-type levels by deletion of speB. These data show that SpxA1 and SpxA2 have opposing roles in virulence and stress resistance, suggesting that they act coordinately to fine-tune toxin expression in response to stress. SpxA2− hypervirulence also shows that stress resistance is not always essential for S. pyogenes pathogenesis in soft tissue

Correlated defects, metal-insulator transition, and magnetic order in ferromagnetic semiconductors

The effect of disorder on transport and magnetization in ferromagnetic III-V semiconductors, in particular (Ga,Mn)As, is studied theoretically. We show that Coulomb-induced correlations of the defect positions are crucial for the transport and magnetic properties of these highly compensated materials. We employ Monte Carlo simulations to obtain the correlated defect distributions. Exact diagonalization gives reasonable results for the spectrum of valence-band holes and the metal-insulator transition only for correlated disorder. Finally, we show that the mean-field magnetization also depends crucially on defect correlations.Comment: 4 pages RevTeX4, 5 figures include

Inverse-kinematics one-neutron pickup with fast rare-isotope beams

New measurements and reaction model calculations are reported for single neutron pickup reactions onto a fast \nuc{22}{Mg} secondary beam at 84 MeV per nucleon. Measurements were made on both carbon and beryllium targets, having very different structures, allowing a first investigation of the likely nature of the pickup reaction mechanism. The measurements involve thick reaction targets and $\gamma$-ray spectroscopy of the projectile-like reaction residue for final-state resolution, that permit experiments with low incident beam rates compared to traditional low-energy transfer reactions. From measured longitudinal momentum distributions we show that the \nuc{12}{C} (\nuc{22}{Mg},\nuc{23}{Mg}+\gamma)X reaction largely proceeds as a direct two-body reaction, the neutron transfer producing bound \nuc{11}{C} target residues. The corresponding reaction on the \nuc{9}{Be} target seems to largely leave the \nuc{8}{Be} residual nucleus unbound at excitation energies high in the continuum. We discuss the possible use of such fast-beam one-neutron pickup reactions to track single-particle strength in exotic nuclei, and also their expected sensitivity to neutron high-$\ell$ (intruder) states which are often direct indicators of shell evolution and the disappearance of magic numbers in the exotic regime.Comment: 8 pages, 5 figure

Gain limits of a Thick GEM in high-purity Ne, Ar and Xe

The dependence of the avalanche charge gain in Thick Gas Electron Multipliers (THGEM) on the purity of Ne, Ar and Xe filling gases was investigated. The gain, measured with alpha-particles in standard conditions (atmospheric pressure, room temperature), was found to considerably drop in gases purified by non-evaporable getters. On the other hand, small N2 admixtures to noble gases resulted in high reachable gains. The results are of general relevance in the operation of gas-avalanche detectors in noble gases, particularly that of two-phase cryogenic detectors for rare events.Comment: 15 pages, 6 figures, submitted to JINS

A Priori Analysis of a Compressible Flamelet Model using RANS Data for a Dual-Mode Scramjet Combustor

In an effort to make large eddy simulation of hydrocarbon-fueled scramjet combustors more computationally accessible using realistic chemical reaction mechanisms, a compressible flamelet/progress variable (FPV) model was proposed that extends current FPV model formulations to high-speed, compressible flows. Development of this model relied on observations garnered from an a priori analysis of the Reynolds-Averaged Navier-Stokes (RANS) data obtained for the Hypersonic International Flight Research and Experimentation (HI-FiRE) dual-mode scramjet combustor. The RANS data were obtained using a reduced chemical mechanism for the combustion of a JP-7 surrogate and were validated using avail- able experimental data. These RANS data were then post-processed to obtain, in an a priori fashion, the scalar fields corresponding to an FPV-based modeling approach. In the current work, in addition to the proposed compressible flamelet model, a standard incompressible FPV model was also considered. Several candidate progress variables were investigated for their ability to recover static temperature and major and minor product species. The effects of pressure and temperature on the tabulated progress variable source term were characterized, and model coupling terms embedded in the Reynolds- averaged Navier-Stokes equations were studied. Finally, results for the novel compressible flamelet/progress variable model were presented to demonstrate the improvement attained by modeling the effects of pressure and flamelet boundary conditions on the combustion

Transcription-associated breaks in Xeroderma Pigmentosum group D cells from patients with combined features of Xeroderma Pigmentosum and Cockayne Syndrome

Defects in the XPD gene can result in several clinical phenotypes, including xeroderma pigmentosum (XP), trichothiodystrophy, and, less frequently, the combined phenotype of XP and Cockayne syndrome (XP-D/CS). We previously showed that in cells from two XP-D/CS patients, breaks were introduced into cellular DNA on exposure to UV damage, but these breaks were not at the sites of the damage. In the present work, we show that three further XP-D/CS patients show the same peculiar breakage phenomenon. We show that these breaks can be visualized inside the cells by immunofluorescence using antibodies to either gamma-H2AX or poly-ADP-ribose and that they can be generated by the introduction of plasmids harboring methylation or oxidative damage as well as by UV photoproducts. Inhibition of RNA polymerase II transcription by four different inhibitors dramatically reduced the number of UV-induced breaks. Furthermore, the breaks were dependent on the nucleotide excision repair (NER) machinery. These data are consistent with our hypothesis that the NER machinery introduces the breaks at sites of transcription initiation. During transcription in UV-irradiated XP-D/CS cells, phosphorylation of the carboxy-terminal domain of RNA polymerase II occurred normally, but the elongating form of the polymerase remained blocked at lesions and was eventually degraded

Towards Spectral Classification of L and T Dwarfs: Infrared and Optical Spectroscopy and Analysis

We present 0.6-2.5um, R~400 spectra of twenty-seven cool, low luminosity stars and substellar objects. Based on these and previously published spectra we develop a preliminary spectral classification system for L and T dwarfs. For late L and T types the classification system is based entirely on four spectral indices in the 1-2.5um interval. Two of these indices are derived from water absorption bands at 1.15um and 1.4um, the latter of which shows a smooth increase in depth through the L and T sequences and can be used to classify both spectral types. The other two indices make use of methane absorption features in the H and K bands, with the K band index also applicable to mid to late L dwarfs. Continuum indices shortward of 1um used by previous authors to classify L dwarfs are found to be useful only through mid L subclasses. We employ the 1.5um water index and the 2.2um methane index to complete the L classification through L9.5 and to link the new system with a modified version of the 2MASS ``Color-d'' index. By correlating the depths of the methane and water absorption features, we establish a T spectral sequence from types T0 to T8, based on all four indices, which is a smooth continuation of the L sequence. We reclassify two 2MASS L8 dwarfs as L9 and L9.5 and identify one SDSS object as L9. In the proposed system methane absorption appears in the K band approximately at L8, two subclasses earlier than its appearance in the H band. The L and T spectral classes are distinguished by the absence and presence, respectively, of H band methane absorption.Comment: 40 pages, 14 figures, to be published in Ap.J., Jan 1, 200