623 research outputs found

    The Anti-Sigma Factor MucA of Pseudomonas aeruginosa: Dramatic Differences of a mucA22 vs. a ΔmucA Mutant in Anaerobic Acidified Nitrite Sensitivity of Planktonic and Biofilm Bacteria in vitro and During Chronic Murine Lung Infection

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    Mucoid mucA22 Pseudomonas aeruginosa (PA) is an opportunistic lung pathogen of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients that is highly sensitive to acidified nitrite (A-NO2-). In this study, we first screened PA mutant strains for sensitivity or resistance to 20 mM A-NO2- under anaerobic conditions that represent the chronic stages of the aforementioned diseases. Mutants found to be sensitive to A-NO2- included PA0964 (pmpR, PQS biosynthesis), PA4455 (probable ABC transporter permease), katA (major catalase, KatA) and rhlR (quorum sensing regulator). In contrast, mutants lacking PA0450 (a putative phosphate transporter) and PA1505 (moaA2) were A-NO2- resistant. However, we were puzzled when we discovered that mucA22 mutant bacteria, a frequently isolated mucA allele in CF and to a lesser extent COPD, were more sensitive to A-NO2- than a truncated ΔmucA deletion (Δ157–194) mutant in planktonic and biofilm culture, as well as during a chronic murine lung infection. Subsequent transcriptional profiling of anaerobic, A-NO2--treated bacteria revealed restoration of near wild-type transcript levels of protective NO2- and nitric oxide (NO) reductase (nirS and norCB, respectively) in the ΔmucA mutant in contrast to extremely low levels in the A-NO2--sensitive mucA22 mutant. Proteins that were S-nitrosylated by NO derived from A-NO2- reduction in the sensitive mucA22 strain were those involved in anaerobic respiration (NirQ, NirS), pyruvate fermentation (UspK), global gene regulation (Vfr), the TCA cycle (succinate dehydrogenase, SdhB) and several double mutants were even more sensitive to A-NO2-. Bioinformatic-based data point to future studies designed to elucidate potential cellular binding partners for MucA and MucA22. Given that A-NO2- is a potentially viable treatment strategy to combat PA and other infections, this study offers novel developments as to how clinicians might better treat problematic PA infections in COPD and CF airway diseases

    Complete moduli of cubic threefolds and their intermediate Jacobians

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    The intermediate Jacobian map, which associates to a smooth cubic threefold its intermediate Jacobian, does not extend to the GIT compactification of the space of cubic threefolds, not even as a map to the Satake compactification of the moduli space of principally polarized abelian fivefolds. A much better "wonderful" compactification of the space of cubic threefolds was constructed by the first and fourth authors --- it has a modular interpretation, and divisorial normal crossing boundary. We prove that the intermediate Jacobian map extends to a morphism from the wonderful compactification to the second Voronoi toroidal compactification of the moduli of principally polarized abelian fivefolds --- the first and fourth author previously showed that it extends to the Satake compactification. Since the second Voronoi compactification has a modular interpretation, our extended intermediate Jacobian map encodes all of the geometric information about the degenerations of intermediate Jacobians, and allows for the study of the geometry of cubic threefolds via degeneration techniques. As one application we give a complete classification of all degenerations of intermediate Jacobians of cubic threefolds of torus rank 1 and 2.Comment: 56 pages; v2: multiple updates and clarification in response to detailed referee's comment

    Stability conditions and positivity of invariants of fibrations

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    We study three methods that prove the positivity of a natural numerical invariant associated to 11-parameter families of polarized varieties. All these methods involve different stability conditions. In dimension 2 we prove that there is a natural connection between them, related to a yet another stability condition, the linear stability. Finally we make some speculations and prove new results in higher dimension.Comment: Final version, to appear in the Springer volume dedicated to Klaus Hulek on the occasion of his 60-th birthda

    Campana points of bounded height on vector group compactifications

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    We initiate a systematic quantitative study of subsets of rational points that are integral with respect to a weighted boundary divisor on Fano orbifolds. We call the points in these sets Campana points. Earlier work of Campana and subsequently Abramovich shows that there are several reasonable competing definitions for Campana points. We use a version that delineates well different types of behaviour of points as the weights on the boundary divisor vary. This prompts a Manin-type conjecture on Fano orbifolds for sets of Campana points that satisfy a klt (Kawamata log terminal) condition. By importing work of Chambert-Loir and Tschinkel to our set-up, we prove a log version of Manin's conjecture for klt Campana points on equivariant compactifications of vector groups.Comment: 52 pages; minor revision, changes in the definition of Campana point

    Finite Hilbert stability of (bi)canonical curves

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    We prove that a generic canonically or bicanonically embedded smooth curve has semistable m-th Hilbert points for all m. We also prove that a generic bicanonically embedded smooth curve has stable m-th Hilbert points for all m \geq 3. In the canonical case, this is accomplished by proving finite Hilbert semistability of special singular curves with G_m-action, namely the canonically embedded balanced ribbon and the canonically embedded balanced double A_{2k+1}-curve. In the bicanonical case, we prove finite Hilbert stability of special hyperelliptic curves, namely Wiman curves. Finally, we give examples of canonically embedded smooth curves whose m-th Hilbert points are non-semistable for low values of m, but become semistable past a definite threshold. (This paper subsumes the previous submission and arXiv:1110.5960).Comment: To appear in Inventiones Mathematicae, 2012. The final publication is available at http://www.springerlink.co

    Taking up the cudgels against gay rights? Trends and trajectories in African Christian theologies on homosexuality

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    Against the background of the HIV epidemic and the intense public controversy on homosexuality in African societies, this article investigates the discourses of academic African Christian theologians on homosexuality. Distinguishing some major strands in African theology, that is, inculturation, liberation, women’s and reconstruction theology, the article examines how the central concepts of culture, liberation, justice, and human rights function in these discourses. On the basis of a qualitative analysis of a large number of publications, the article shows that stances of African theologians are varying from silence and rejection to acceptance. Although many African theologians have taken up the cudgels against gay rights, some “dissident voices” break the taboo and develop more inclusive concepts of African identity and African Christianity

    Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

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    Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5
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