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From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity
Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway
Ion optics in a 14 UD Pelletron terminal
The terminal of the Pelletron accelerator in Rehovot was designed so as to transmit freely any beam of a desired charge state through the high energy acceleration tube. Charge selection is accomplished by means of a displaced electrostatic quadrupole triplet. A matching lens further downstream inside the terminal is matching the beam emittance to the high energy tube acceptance. A detailed study of the angular acceptance of the high energy tube was carried out in order to check for possible tube loading. The transmission through the high energy tube is substantially improved by the matching lens both when the charge selector is on and when it is off
Ion optics in a 14 UD Pelletron terminal
The terminal of the Pelletron accelerator in Rehovot was designed so as to transmit freely any beam of a desired charge state through the high energy acceleration tube. Charge selection is accomplished by means of a displaced electrostatic quadrupole triplet. A matching lens further downstream inside the terminal is matching the beam emittance to the high energy tube acceptance. A detailed study of the angular acceptance of the high energy tube was carried out in order to check for possible tube loading. The transmission through the high energy tube is substantially improved by the matching lens both when the charge selector is on and when it is off.Le terminal de l'accélérateur Pelletron de Rehovot est prévu pour transmettre tout faisceau ayant l'état de charge désiré à travers le tube haute énergie. La sélection de charge est obtenue au moyen d'un triplet quadrupolaire électrostatique déplacé. Une lentille d'adaptation en aval dans le terminal adapte l'émittance du faisceau à l'acceptance du tube haute énergie. Une étude détaillée de l'acceptance angulaire du tube haute énergie a été effectuée en vue de vérifier une éventuelle charge du tube. La transmission à travers le tube haute énergie est fortement améliorée par la lentille d'adaptation lorsque le sélecteur de charge est en service mais également lorsqu'il n'est pas utilisé