In-Vivo Expression Profiling of Pseudomonas aeruginosa Infections Reveals Niche-Specific and Strain-Independent Transcriptional Programs

Pseudomonas aeruginosa is a threatening, opportunistic pathogen causing disease in immunocompromised individuals. The hallmark of P. aeruginosa virulence is its multi-factorial and combinatorial nature. It renders such bacteria infectious for many organisms and it is often resistant to antibiotics. To gain insights into the physiology of P. aeruginosa during infection, we assessed the transcriptional programs of three different P. aeruginosa strains directly after isolation from burn wounds of humans. We compared the programs to those of the same strains using two infection models: a plant model, which consisted of the infection of the midrib of lettuce leaves, and a murine tumor model, which was obtained by infection of mice with an induced tumor in the abdomen. All control conditions of P. aeruginosa cells growing in suspension and as a biofilm were added to the analysis. We found that these different P. aeruginosa strains express a pool of distinct genetic traits that are activated under particular infection conditions regardless of their genetic variability. The knowledge herein generated will advance our understanding of P. aeruginosa virulence and provide valuable cues for the definition of prospective targets to develop novel intervention strategies

Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.A multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies

Comparative population genetic structure of the endangered southern brown bandicoot, Isoodon obesulus, in fragmented landscapes of Southern Australia

Genetic connectivity is a key factor for maintaining the persistence of populations in fragmented landscapes. In highly modified landscapes such us peri-urban areas, organisms' dispersal among fragmented habitat patches can be reduced due to the surrounding matrix, leading to subsequent decreased gene flow and increased potential extinction risk in isolated sub-populations. However, few studies have compared within species how dispersal/gene flow varies between regions and among different forms of matrix that might be encountered. In the current study, we investigated gene flow and dispersal in an endangered marsupial, the southern brown bandicoot (Isoodon obesulus) in a heavily modified peri-urban landscape in South Australia, Australia. We used 14 microsatellite markers to genotype 254 individuals which were sampled from 15 sites. Analyses revealed significant genetic structure. Our analyses also indicated that dispersal was mostly limited to neighbouring sites. Comparisons of these results with analyses of a different population of the same species revealed that gene flow/dispersal was more limited in this peri-urban landscape than in a pine plantation landscape approximately 400 km to the south-east. These findings increase our understanding of how the nature of fragmentation can lead to profound differences in levels of genetic connectivity among populations of the same species.You Li, Steven J.B. Cooper, Melanie L. Lancaster, Jasmin G. Packer, Susan M. Carthe

Production of Polarized N-12 With the C-12(p,N-12)n0 Reaction

The polarization transferred to N-12 in the C-12(p -->, N-12 -->)n0 reaction has been measured at E(p) = 50 and 72 MeV. In agreement with previous work, the N-12 polarization was a strong function of the material in which the ions stop, implying a complex depolarization mechanism. The largest nuclear polarization observed, P0 = 0.260 +/- 0.002, was for N-12 implanted in Al. This result gives the lower bound K(y)y' greater-than-or-equal-to 0.377 +/- 0.003 for the transverse polarization-transfer coefficient. Distorted-wave calculations predict K(y)y' should be approximately 2/3. The angular distribution of K(y)y' at E(p) = 72 MeV is nearly isotropic, in agreement with the distorted-wave prediction. The electronic polarization relaxation time T1 for N-12 implanted in C, Al, Ni and Au was found to be approximately constant and much longer than the N-12 half-life; viz., T1 = 0.150 +/- 0.014 s

The Polarization Asymmetry Correlation of In-107 and Parity Violation

We report on the first measurements of the longitudinal polarization of positrons emitted by polarized nuclei, using cryogenically polarized 107In. This so-called polarization-asymmetry correlation is very sensitive to the mass of a possible right-handed gauge boson, which is invoked by parity symmetric extensions of the standard V-A electroweak model to explain the experimentally observed strong violation of parity which, however, may not be complete. The positron polarization is deduced from the time-resolved decay spectrum of positronium hyperfine states. Our preliminary result points to a lower limit of about 210 GeV for the mass of an eventual right-handed charged W gauge boson. This result can still be improved

BOUNDS ON RIGHT-HANDED CURRENTS FROM A RELATIVE BETA-POLARIZATION MEASUREMENT WITH POLARIZED IN-107

The first measurements of the longitudinal polarization of positrons emitted by polarized 107In are reported. The positron polarization is deduced from the time-resolved decay spectrum of positronium hyperfine states. Our result is in agreement with the standard electro-weak model and provides a new lower limit for the mass of an eventual, predominantly right-handed charged W-gauge boson of 220 GeV/c2

BOUNDS ON RIGHT-HANDED CURRENTS FROM A RELATIVE BETA-POLARIZATION MEASUREMENT WITH POLARIZED IN-107

The first measurements of the longitudinal polarization of positrons emitted by polarized 107In are reported. The positron polarization is deduced from the time-resolved decay spectrum of positronium hyperfine states. Our result is in agreement with the standard electro-weak model and provides a new lower limit for the mass of an eventual, predominantly right-handed charged W-gauge boson of 220 GeV/c2

STUDY OF THE VIOLATION OF PARITY IN NUCLEAR BETA-DECAY VIA A RELATIVE BETA-POLARIZATION MEASUREMENT WITH POLARIZED IN-107 NUCLEI

The first measurements of the longitudinal polarization of positrons emitted by polarized107In are reported. The positron polarization is deduced from the time-resolved decay spectrum of positronium hyerfine states. Our result is in agreement with the standard electroweak model and provides a new lower limit for the mass of an eventual, predominantly right-handed charged W gauge boson of 220 GeV/c 2

Search for physics beyond the standard model via a polarization-asymmetry correlation experiment on In-107

We report on a new precision measurement of the longitudinal polarization of positrons emitted by polarized 107In nuclei. If interpreted in the framework of the manifest left-right symmetric model, preliminary results yield a lower limit of 303 GeV/c2 for the mass of a possible, predominantly right-handed W gauge boson