Transposon Insertion Sequencing Elucidates Novel Gene Involvement in Susceptibility and Resistance to Phages T4 and T7 in Escherichia coli O157.

Experiments using bacteriophage (phage) to infect bacterial strains have helped define some basic genetic concepts in microbiology, but our understanding of the complexity of bacterium-phage interactions is still limited. As the global threat of antibiotic resistance continues to increase, phage therapy has reemerged as an attractive alternative or supplement to treating antibiotic-resistant bacterial infections. Further, the long-used method of phage typing to classify bacterial strains is being replaced by molecular genetic techniques. Thus, there is a growing need for a complete understanding of the precise molecular mechanisms underpinning phage-bacterium interactions to optimize phage therapy for the clinic as well as for retrospectively interpreting phage typing data on the molecular level. In this study, a genomics-based fitness assay (TraDIS) was used to identify all host genes involved in phage susceptibility and resistance for a T4 phage infecting Shiga-toxigenic Escherichia coli O157. The TraDIS results identified both established and previously unidentified genes involved in phage infection, and a subset were confirmed by site-directed mutagenesis and phenotypic testing of 14 T4 and 2 T7 phages. For the first time, the entire sap operon was implicated in phage susceptibility and, conversely, the stringent starvation protein A gene (sspA) was shown to provide phage resistance. Identifying genes involved in phage infection and replication should facilitate the selection of bespoke phage combinations to target specific bacterial pathogens.IMPORTANCE Antibiotic resistance has diminished treatment options for many common bacterial infections. Phage therapy is an alternative option that was once popularly used across Europe to kill bacteria within humans. Phage therapy acts by using highly specific viruses (called phages) that infect and lyse certain bacterial species to treat the infection. Whole-genome sequencing has allowed modernization of the investigations into phage-bacterium interactions. Here, using E. coli O157 and T4 bacteriophage as a model, we have exploited a genome-wide fitness assay to investigate all genes involved in defining phage resistance or susceptibility. This knowledge of the genetic determinants of phage resistance and susceptibility can be used to design bespoke phage combinations targeted to specific bacterial infections for successful infection eradication.This work was supported by the Wellcome Trust (grant number WT098051). A.K.C. and C.J.B. were supported by the Medical Research Council (grant number G1100100/1). D.L.G. and A.S.L. were supported by BBSRC (UKRI) funding (programme number P013740)

BPS States on M5-brane in Large C-field Background

We extensively study BPS solutions of the low energy effective theory of M5-brane in large C-field background. This provides us an opportunity to explore the interactions turned on by C-field background through the Nambu-Poisson structure. The BPS states considered in this paper include the M-waves, the self-dual string (M2 ending on M5), tilted M5-brane, holomorphic embedding of M5-brane and the intersection of two M5-branes along a 3-brane.Comment: 25 pages, reference adde

Evolutive Unification in Composite Active Galactic Nuclei

In this paper we explore an evolutionary Unified scenario involving super massive black hole and starburst with outflow, that seems capable of explaining most of the observational properties of at least part of AGNs. Our suggestion is explored inside the expectations of the Starburst model close associated with the AGN where the NLR, BLR and BAL region are produced in part by the outflow process with shells and in compact supernova remnants. The outflow process in BAL QSOs with extreme IR and Fe II emission is studied. In addition, the Fe II poblem regarding the BLR of AGN is analysed. Neither the correlations between the BAL, IR emission, FeII intensity and the intrinsic properties of the AGN are clearly understood. We suggest here that the behaviour of the BAL, IR and FeII emission in AGNs can be understood inside an evolutionary and composite model for AGNs. In our model, strong BAL systems and Fe II emission are present (and intense) in young IR objects. Orientation/ obscuration effects take the role of a second parameter providing the segregation between Sy1/Sy2 and BLRG/NLRG.Comment: 14 pages, 6 figures (submitted MNRAS

The formation of broad emission line regions in supernova-QSO wind interactions: II. 2D calculations

One aspect of supernova remnant evolution that is relatively unstudied is the influence of an AGN environment. A high density ambient medium and a nearby powerful continuum source will assist the cooling of shocked ejecta and swept-up gas. Motion of the surrounding medium relative to the remnant will also affect the remnant morphology. In an extension to previous work we have performed 2D hydrodynamical calculations of SNR evolution in an AGN environment, and have determined the evolutionary behaviour of cold gas in the remnant. The cold gas will contribute to the observed broad line emission in AGNs, and we present preliminary theoretical line profiles from our calculations. A more detailed comparison with observations will be performed in future work. The SNR-AGN interaction may be also useful as a diagnostic of AGN winds

Magnetic helicity in primordial and dynamo scenarios of galaxies

Some common properties of helical magnetic fields in decaying and driven turbulence are discussed. These include mainly the inverse cascade that produces fields on progressively larger scales. Magnetic helicity also restricts the evolution of the large scale field: the field decays less rapidly than a non-helical field, but it also saturates more slowly, i.e. on a resistive time scale if there are no magnetic helicity fluxes. The former effect is utilized in primordial field scenarios, while the latter is important for successfully explaining astrophysical dynamos that saturate faster than resistively. Dynamo action is argued to be important not only in the galactic dynamo, but also in accretion discs in active galactic nuclei and around protostars, both of which contribute to producing a strong enough seed magnetic field. Although primordial magnetic fields may be too weak to compete with these astrophysical mechanisms, such fields could perhaps still be important in producing polarization effects in the cosmic background radiation.Comment: 8 pages, 5 figures, talk given in Bologna, August 2006, proceedings of "The Origin and Evolution of Cosmic Magnetism", Astron. Nachr. (in press

An Open Letter to Congressman Gingrich

We urge you to reconsider your proposal to amend the House Rules to require a three-fifths vote for enactment of laws that increase income taxes. This proposal violates the explicit intentions of the Framers. It is inconsistent with the Constitution\u27s language and structure. It departs sharply from traditional congressional practice. It may generate constitutional litigation that will encourage Supreme Court intervention in an area best left to responsible congressional decision. Unless the proposal is withdrawn now, it will serve as an unfortunate precedent for the proliferation of supermajority rules on a host of different subjects in the future. Over time, we will see the continuing erosion of our central constitutional commitments to majority rule and deliberative democracy

Boundary Conditions for Interacting Membranes

We investigate supersymmetric boundary conditions in both the Bagger-Lambert and the ABJM theories of interacting membranes. We find boundary conditions associated to the fivebrane, the ninebrane and the M-theory wave. For the ABJM theory we are able to understand the enhancement of supersymmetry to produce the (4,4) supersymmetry of the self-dual string. We also include supersymmetric boundary conditions on the gauge fields that cancel the classical gauge anomaly of the Chern-Simons terms.Comment: 36 pages, latex, v2 minor typos correcte

GEMINI 3D spectroscopy of BAL+IR+Fe II QSOs: II. IRAS 04505-2958 an explosive QSO with hypershell and a new scenario for galaxy formation and galaxy end

From a study of BAL + IR + Fe II QSOs (using deep Gemini GMOS-IFU spectroscopy) new results are presented: for IRAS 04505-2958. Specifically, we have studied in detail the out flow (OF) process and their associated structures, mainly at two large galactic scales: (i) two blobs/shells (S1, S2) at radius r = 1.1 and 2.2 kpc; and (ii) an external hypergiant shell (S3) at r = 11 kpc. In addition, the presence of two very extended hypergiant shells (S4, S5) at r = 80 kpc is discussed. From this GMOS study the following main results were obtained: (i) For the external hypergiant shell S3 the kinematics GMOS maps of the ionized gas show very similar features to those observed for the prototype of exploding external supergiant shell: in NGC 5514. (ii) The main knots K1, K2 and K3 -of this hypergiant shell S3- show a stellar population and emission line ratios associated with the presence of a starburst + OF/shocks. (iii) The internal shells S1 and S2 show structures, OF components and properties very similar to those detected in the nuclear shells of Mrk 231. (iv) The shells S1+S2 and S3 are aligned at PA = 131: i.e. suggesting that the OF process is in the blow-out phase with bipolar structure. In addition, the shells S4 and S5 (at 80-100 kpc scale) are aligned at PA = 40, i.e.: a bipolar OF perpendicular to the internal OF. Finally, the generation of UHE cosmic rays and neutrino/ dark-matter -associated with HyNe in BAL + IR + Fe II QSOs- is discussed.Comment: Submitted MNRAS, 81 pages, 25 Figure

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: Implications for radiation dose escalation in carcinoma of the pancreas

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel