An ABC Transporter Is Required for Secretion of Peptide Sex Pheromones in Enterococcus faecalis

ABSTRACT Enterococci are leading causes of hospital-acquired infection in the United States and continue to develop resistances to new antibiotics. Many Enterococcus faecalis isolates harbor pheromone-responsive plasmids that mediate horizontal transfer of even large blocks of chromosomal genes, resulting in hospital-adapted strains over a quarter of whose genomes consist of mobile elements. Pheromones to which the donor cells respond derive from lipoprotein signal peptides. Using a novel bacterial killing assay dependent on the presence of sex pheromones, we screened a transposon mutant library for functions that relate to the production and/or activity of the effector pheromone. Here we describe a previously uncharacterized, but well-conserved, ABC transporter that contributes to pheromone production. Using three distinct pheromone-dependent mating systems, we show that mutants defective in expressing this transporter display a 5- to 6-order-of-magnitude reduction in conjugation efficiency. In addition, we demonstrate that the ABC transporter mutant displays an altered biofilm architecture, with a significant reduction in biofilm biomass compared to that of its isogenic parent, suggesting that pheromone activity also influences biofilm development. The conservation of this peptide transporter across the Firmicutes suggests that it may also play an important role in cell-cell communication in other species within this important phylum

Optics Considerations for the PS2

CERN envisages replacing the existing Proton Synchrotron (PS) with a larger synchrotron (PS2) capable of injecting at higher energy into the SPS. Since it should increase the performance not only of the LHC but also CNGS and other users of beams from CERN's hadron injector complex, the new accelerator must retain much of the flexibility of the present complex. A number of candidate optics, with and without transition crossing, have been evaluated systematically and compared

Distribution Pattern Variability of Granular VRT Applicators

Granular applicators equipped with variable-rate technology (VRT) have gained popularity in recent years as a result of increased interest in variable-rate application. The purpose of this investigation was to characterize distribution patterns at varying rates for different granular applicators. Uniform-rate (UR) tests were conducted to assess the accuracy of variable-rate application from four granular applicators: two spinner-disc spreaders (A and B), and two pneumatic applicators (C and D). Pattern results indicated a consistent triangular pattern for spinner spreader B and consistent patterns for the pneumatic applicators (C and D). However, applicator D produced pattern variations at the center and right side. Simulated overlap analysis generated CVs \u3c 20% for applicators B and C. Applicator A performed well at the two lower rates (CVs \u3c 19%) but not at the highest rate (CV = 27%). Pattern unevenness for applicator D produced CVs between 25% and 34%. The spinner-disc spreaders over-applied, while the pneumatic applicators under-applied at the margins, suggesting an adjustment to the effective swath spacing or spinner-disc speed is needed to improve application accuracy. Further, overlap plots indicated pattern variability even when acceptable CVs were attained for applicators B and C. Therefore, it is recommended that CVs accompany simulated overlap pattern plots to ensure proper calibration of VRT equipment. Swath spacing analysis indicated that three of the four applicator spacings could be changed from the recommended value to improve application uniformity. Pattern comparisons showed that pattern shifts occurred for applicator A (P = 0.0092) with increasing application rate but not for applicators B, C, and D. These results demonstrate potential application errors with VRT and the need for proper calibration to maintain acceptable performance. Further, this investigation demonstrates the need for a VRT equipment testing standard

Linear Optics Design for PS2

The design considerations and key parameters for the replacement of the CERN Proton Synchrotron (PS) with a new ring (PS2), as part of the upgrade of the LHC injector complex are summarized. Classical linear optics solutions including standard FODO, doublet and triplet cells with real transition energy, are studied. Particular emphasis is given to the tuning and optimisation of Negative Momentum Compaction (NMC) cells with imaginary transition energy. The optics of the high energy transfer line is also presented

Anatomy ontologies and potential users: bridging the gap.

MOTIVATION: To evaluate how well current anatomical ontologies fit the way real-world users apply anatomy terms in their data annotations. METHODS: Annotations from three diverse multi-species public-domain datasets provided a set of use cases for matching anatomical terms in two major anatomical ontologies (the Foundational Model of Anatomy and Uberon), using two lexical-matching applications (Zooma and Ontology Mapper). RESULTS: Approximately 1500 terms were identified; Uberon/Zooma mappings provided 286 matches, compared to the control and Ontology Mapper returned 319 matches. For the Foundational Model of Anatomy, Zooma returned 312 matches, and Ontology Mapper returned 397. CONCLUSIONS: Our results indicate that for our datasets the anatomical entities or concepts are embedded in user-generated complex terms, and while lexical mapping works, anatomy ontologies do not provide the majority of terms users supply when annotating data. Provision of searchable cross-products for compositional terms is a key requirement for using ontologies.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

CD4 inhibits helper T cell activation at lower affinity threshold for full-length T cell receptors than single chain signaling constructs

CD

Clusters of internally primed transcripts reveal novel long noncoding RNAs

Non- protein- coding RNAs ( ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25- nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases ( Kb), respectively. We surveyed the 102,801 FANTOM3 mouse cDNA clones and found that Air and Xist were present not as single, full- length transcripts but as a cluster of multiple, shorter cDNAs, which were unspliced, had little coding potential, and were most likely primed from internal adenine- rich regions within longer parental transcripts. We therefore conducted a genome- wide search for regional clusters of such cDNAs to find novel macro ncRNA candidates. Sixty- six regions were identified, each of which mapped outside known protein- coding loci and which had a mean length of 92 Kb. We detected several known long ncRNAs within these regions, supporting the basic rationale of our approach. In silico analysis showed that many regions had evidence of imprinting and/ or antisense transcription. These regions were significantly associated with microRNAs and transcripts from the central nervous system. We selected eight novel regions for experimental validation by northern blot and RT- PCR and found that the majority represent previously unrecognized noncoding transcripts that are at least 10 Kb in size and predominantly localized in the nucleus. Taken together, the data not only identify multiple new ncRNAs but also suggest the existence of many more macro ncRNAs like Xist and Air

Solutions of the sDiff(2)Toda equation with SU(2) Symmetry

We present the general solution to the Plebanski equation for an H-space that admits Killing vectors for an entire SU(2) of symmetries, which is therefore also the general solution of the sDiff(2)Toda equation that allows these symmetries. Desiring these solutions as a bridge toward the future for yet more general solutions of the sDiff(2)Toda equation, we generalize the earlier work of Olivier, on the Atiyah-Hitchin metric, and re-formulate work of Babich and Korotkin, and Tod, on the Bianchi IX approach to a metric with an SU(2) of symmetries. We also give careful delineations of the conformal transformations required to ensure that a metric of Bianchi IX type has zero Ricci tensor, so that it is a self-dual, vacuum solution of the complex-valued version of Einstein's equations, as appropriate for the original Plebanski equation.Comment: 27 page

Prevention of chronic rejection in mouse aortic allografts by combined treatment with CTLA4-Ig and anti-CD40 ligand monoclonal antibody

Background. In this study, using a murine model of aortic allotransplantation, the role of blockade of signaling through CD28/B7 and CD40/CD40 ligand costimulatory pathways in the evolvement of posttransplant vasculopathy was examined. Methods. Aortic allografts were transplanted across C57BL/10J (H2b)→C3H (H2(k)) strain combinations. Transient or more stable blockade of second signaling was achieved by either a single injection or multiple injections of CTLA4-Ig fusion protein (200 μg/dose i.p.) and/or anti-CD40 ligand (CD40L) monoclonal antibody (250 μg i.m.). At day 30 after transplantation, the grafts were harvested for histopathological and immunohistochemical examination. Results. Similar to allografts of untreated animals, aortic allografts obtained from recipients treated with either CTLA4-Ig or anti-CD40L monoclonal antibody alone exhibited marked narrowing of the lumen primarily due to concentric intimal thickening caused by proliferation of α-smooth muscle actin-positive cells. Contemporaneous treatment, however, with either a single injection or multiple injections of CTLA4-Ig and anti-CD40L monoclonal antibody resulted in marked diminution of intimal thickening. Interestingly, concurrent prolonged inhibition of CD28/B7 and CD40/ CD40L pathways resulted in complete abrogation of the development of posttransplant arteriopathy. Conclusion. These data suggest that a more stable disruption of signaling through costimulatory pathways may be required to obviate the development of posttransplant vasculopathy