Cluster J Mycobacteriophages: Intron Splicing in Capsid and Tail Genes

Bacteriophages isolated on Mycobacterium smegmatis mc2155 represent many distinct genomes sharing little or no DNA sequence similarity. The genomes are architecturally mosaic and are replete with genes of unknown function. A new group of genomes sharing substantial nucleotide sequences constitute Cluster J. The six mycobacteriophages forming Cluster J are morphologically members of the Siphoviridae, but have unusually long genomes ranging from 106.3 to 117 kbp. Reconstruction of the capsid by cryo-electron microscopy of mycobacteriophage BAKA reveals an icosahedral structure with a triangulation number of 13. All six phages are temperate and homoimmune, and prophage establishment involves integration into a tRNA-Leu gene not previously identified as a mycobacterial attB site for phage integration. The Cluster J genomes provide two examples of intron splicing within the virion structural genes, one in a major capsid subunit gene, and one in a tail gene. These genomes also contain numerous free-standing HNH homing endonuclease, and comparative analysis reveals how these could contribute to genome mosaicism. The unusual Cluster J genomes provide new insights into phage genome architecture, gene function, capsid structure, gene mobility, intron splicing, and evolution. © 2013 Pope et al

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus

A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules

G Protein-regulated Inducer of Neurite Outgrowth (GRIN) Modulates Sprouty Protein Repression of Mitogen-activated Protein Kinase (MAPK) Activation by Growth Factor Stimulation

Gαo/i interacts directly with GRIN (G protein-regulated inducer of neurite outgrowth). Using the yeast two-hybrid system, we identified Sprouty2 as an interacting partner of GRIN. Gαo and Sprouty2 bind to overlapping regions of GRIN, thus competing for GRIN binding. Imaging experiments demonstrated that Gαo expression promoted GRIN translocation to the plasma membrane, whereas Sprouty2 expression failed to do so. Given the role of Sprouty2 in the regulation of growth factor-mediated MAPK activation, we examined the contribution of the GRIN-Sprouty2 interaction to CB1 cannabinoid receptor regulation of FGF receptor signaling. In Neuro-2A cells, a system that expresses all of the components endogenously, modulation of GRIN levels led to regulation of MAPK activation. Overexpression of GRIN potentiated FGF activation of MAPK and decreased tyrosine phosphorylation of Sprouty2. Pretreatment with Go/i-coupled CB1 receptor agonist attenuated subsequent FGF activation of MAPK. Decreased expression of GRIN both diminished FGF activation of MAPK and blocked CB1R attenuation of MAPK activation. These observations indicate that Gαo interacts with GRIN and outcompetes GRIN from bound Sprouty. Free Sprouty then in turn inhibits growth factor signaling. Thus, here we present a novel mechanism of how Go/i-coupled receptors can inhibit growth factor signaling to MAPK

Controlled production of atomic oxygen and nitrogen in a pulsed radio-frequency atmospheric-pressure plasma

International audienceRadio-frequency driven atmospheric pressure plasmas are efficient sources for the production of reactive species at ambient pressure and close to room temperature. Pulsing the radio-frequency power input provides additional control over species production and gas temperature. Here, we demonstrate the controlled production of highly reactive atomic oxygen and nitrogen in a pulsed radio-frequency ( ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn001.gif] 13.56 MHz) atmospheric-pressure plasma, operated with a small ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn002.gif] 0.1 % air-like admixture ( ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn003.gif] \rm N_2 / ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn004.gif] \rm O_2 at ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn005.gif] 4:1 ) through variations in the duty cycle. Absolute densities of atomic oxygen and nitrogen are determined through vacuum-ultraviolet absorption spectroscopy using the DESIRS beamline at the SOLEIL synchrotron coupled with a high resolution Fourier-transform spectrometer. The neutral-gas temperature is measured using nitrogen molecular optical emission spectroscopy. For a fixed applied-voltage amplitude (234?V), varying the pulse duty cycle from 10% to 100% at a fixed 10?kHz pulse frequency enables us to regulate the densities of atomic oxygen and nitrogen over the ranges of ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn006.gif] (0.18±0.03) ? ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn007.gif] (3.7±0.1)× 10^20 ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn008.gif] \rm m^-3 and ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn009.gif] (0.2±0.06) ? ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn010.gif] (4.4±0.8) × 10^19 ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn011.gif] \rm m^-3 , respectively. The corresponding 11?K increase in the neutral-gas temperature with increased duty cycle, up to a maximum of ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn012.gif] (314±4) K, is relatively small. This additional degree of control, achieved through regulation of the pulse duty cycle and time-averaged power, could be of particular interest for prospective biomedical applications

Comparative genomics of Cluster O mycobacteriophages

Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange

Reproducibility of `COST Reference Microplasma Jets'

Atmospheric pressure plasmas have been ground-breaking for plasma science and technologies, due to their significant application potential in many fields, including medicinal, biological, and environmental applications. This is predominantly due to their efficient production and delivery of chemically reactive species under ambient conditions. One of the challenges in progressing the field is comparing plasma sources and results across the community and the literature. To address this a reference plasma source was established during the `Biomedical Applications of Atmospheric Pressure Plasmas' EU COST Action MP1101. It is crucial that reference sources are reproducible. Here, we present the reproducibility and variance across multiple sources through examining various characteristics, including: absolute atomic oxygen densities, absolute ozone densities, electrical characteristics, optical emission spectroscopy, temperature measurements, and bactericidal activity. The measurements demonstrate that the tested COST jets are mainly reproducible within the intrinsic uncertainty of each measurement technique

Global value trees

The fragmentation of production across countries has become an important feature of the globalization in recent decades and is often conceptualized by the term “global value chains” (GVCs). When empirically investigating the GVCs, previous studies are mainly interested in knowing how global the GVCs are rather than how the GVCs look like. From a complex networks perspective, we use the World Input-Output Database (WIOD) to study the evolution of the global production system. We find that the industry-level GVCs are indeed not chain-like but are better characterized by the tree topology. Hence, we compute the global value trees (GVTs) for all the industries available in the WIOD. Moreover, we compute an industry importance measure based on the GVTs and compare it with other network centrality measures. Finally, we discuss some future applications of the GVTs