Portal protein diversity and phage ecology

© 2008 The Authors. This article is distributed under the terms of the Creative Commons License, Attribution 2.5. The definitive version was published in Environmental Microbiology 10 (2008): 2810-2823, doi:10.1111/j.1462-2920.2008.01702.x.Oceanic phages are critical components of the global ecosystem, where they play a role in microbial mortality and evolution. Our understanding of phage diversity is greatly limited by the lack of useful genetic diversity measures. Previous studies, focusing on myophages that infect the marine cyanobacterium Synechococcus, have used the coliphage T4 portal-protein-encoding homologue, gene 20 (g20), as a diversity marker. These studies revealed 10 sequence clusters, 9 oceanic and 1 freshwater, where only 3 contained cultured representatives. We sequenced g20 from 38 marine myophages isolated using a diversity of Synechococcus and Prochlorococcus hosts to see if any would fall into the clusters that lacked cultured representatives. On the contrary, all fell into the three clusters that already contained sequences from cultured phages. Further, there was no obvious relationship between host of isolation, or host range, and g20 sequence similarity. We next expanded our analyses to all available g20 sequences (769 sequences), which include PCR amplicons from wild uncultured phages, non-PCR amplified sequences identified in the Global Ocean Survey (GOS) metagenomic database, as well as sequences from cultured phages, to evaluate the relationship between g20 sequence clusters and habitat features from which the phage sequences were isolated. Even in this meta-data set, very few sequences fell into the sequence clusters without cultured representatives, suggesting that the latter are very rare, or sequencing artefacts. In contrast, sequences most similar to the culture-containing clusters, the freshwater cluster and two novel clusters, were more highly represented, with one particular culture-containing cluster representing the dominant g20 genotype in the unamplified GOS sequence data. Finally, while some g20 sequences were non-randomly distributed with respect to habitat, there were always numerous exceptions to general patterns, indicating that phage portal proteins are not good predictors of a phage's host or the habitat in which a particular phage may thrive.This research was supported in part by funding from NSF (CMORE contribution #87), DOE, The Seaver Foundation and the Gordon and Betty Moore Foundation Marine Microbiology Program to S.W.C.; an NIH Bioinformatics Training Grant supported M.B.S.; MIT Undergraduate Research Opportunities Program supported V.Q., J.A.L., G.T., R.F. and J.E.R.; Howard Hughes Medical Institute funded MIT Biology Department Undergraduate Research Opportunities Program supported A.S.D.; NSERC (Canada) Discovery Grant (DG 298394) and a Grant from the Canadian Foundation for Innovation (NOF10394) to J.P.B.; NSF Graduate Fellowship funding supported M.L.C

Corrigendum "Portal protein diversity and phage ecology"

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Environmental Microbiology 13 (2011): 2832, doi:10.1111/j.1462-2920.2011.02616.x

Synthesis of Fluorine-18 Functionalized Nanoparticles for use as in vivo Molecular Imaging Agents

Nanoparticles containing fluorine-18 were prepared from block copolymers made by ring opening metathesis polymerization (ROMP). Using the fast initiating ruthenium metathesis catalyst (H_2IMes)(pyr)_2(Cl)_2Ru=CHPh, low polydispersity amphiphilic block copolymers were prepared from a cinnamoyl-containing hydrophobic norbornene monomer and a mesyl-terminated PEG-containing hydrophilic norbornene monomer. Self-assembly into micelles and subsequent cross-linking of the micelle cores by light-activated dimerization of the cinnamoyl groups yielded stable nanoparticles. Incorporation of fluorine-18 was achieved by nucleophilic displacement of the mesylates by the radioactive fluoride ion with 31% incorporation of radioactivity. The resulting positron-emitting nanoparticles are to be used as in vivo molecular imaging agents for use in tumor imaging

Restricted feedback control of one-dimensional maps

Dynamical control of biological systems is often restricted by the practical constraint of unidirectional parameter perturbations. We show that such a restriction introduces surprising complexity to the stability of one-dimensional map systems and can actually improve controllability. We present experimental cardiac control results that support these analyses. Finally, we develop new control algorithms that exploit the structure of the restricted-control stability zones to automatically adapt the control feedback parameter and thereby achieve improved robustness to noise and drifting system parameters.Comment: 29 pages, 9 embedded figure

LUNEX5 : A FEL PROJECT TOWARDS THE FIFTH GENERATION IN FRANCE

ISBN978-3-95450-117-5 - http://accelconf.web.cern.ch/AccelConf/FEL2011/papers/tupa09.pdfInternational audienc

Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice

The sphingolipid ceramide is intimately involved in the growth, differentiation, senescence, and death of normal and cancerous cells. Mitochondria are increasingly appreciated to play a key role in ceramide-induced cell death. Recent work showed the C16-pyridinium ceramide analogue LCL-30 to induce cell death in vitro by mitochondrial targeting. The aim of the current study was to translate these results to an in vivo model. We found that LCL-30 accumulated in mitochondria in the murine colorectal cancer cell line CT-26 and reduced cellular ATP content, leading to dose- and time-dependent cytotoxicity. Although the mitochondrial levels of sphingosine-1-phosphate (S1P) became elevated, transcription levels of ceramide-metabolising enzymes were not affected. In mice, LCL-30 was rapidly absorbed from the peritoneal cavity and cleared from the circulation within 24 h, but local peritoneal toxicity was dose-limiting. In a model of subcutaneous tumour inoculation, LCL-30 significantly reduced the proliferative activity and the growth rate of established tumours. Sphingolipid profiles in tumour tissue also showed increased levels of S1P. In summary, we present the first in vivo application of a long-chain pyridinium ceramide for the treatment of experimental metastatic colorectal cancer, together with its pharmacokinetic parameters. LCL-30 was an efficacious and safe agent. Future studies should identify an improved application route and effective partners for combination treatment

High repetition-rate electro-optic sampling: Recent studies using photonic time-stretch

Single-shot electro-optic sampling (EOS) is a powerful characterization tool for monitoring the shape of electron bunches, and coherent synchrotron radiation pulses. For reaching high acquisition rates, an efficient possibility consists to associate classic EOS systems with the so-called photonic time-stretch technique [1]. We present recent results obtained at SOLEIL and ANKA using this strategy. In particular, we show how a high sensitivity variant of photonic time stretch [2] EOS enabled to monitor the CSR pulses emitted by short electron bunches at SOLEIL [3]. We could thus confirm in a very direct way the theories predicting an interplay between two physical processes. Below a critical bunch charge, we observe a train of identical THz pulses stemming from the shortness of the electron bunches. Above this threshold, CSR emission is dominated by drifting structures appearing through spontaneous self-organization. We also consider the association of time-stretch and EOS for recording electron bunch near fields at high repetition rate. We present preliminary results obtained at ANKA, aiming at recording the electron bunch shape evolution during the microbunching instability