Pulse phase resolved analysis of the HMXB Cen X-3 over two binary orbits

We present a detailed analysis of observations of the high mass X-ray binary Cen X-3 spanning two consecutive binary orbits performed with the RXTE satellite in early March 1997. The PCA and HEXTE light curves both show a clear reduction in count rate after mid-orbit for both binary revolutions. We therefore analyze two broad band spectra for each orbit, before and after mid-orbit. Consistent with earlier observations these four joint PCA and HEXTE spectra can be well described using a phenomenological pulsar continuum model, including an iron emission line and a cyclotron resonance scattering feature. While no strong spectral variations were detected, the second half of orbit 2 shows a tendency toward being softer and more strongly absorbed. In order to follow the orbital phase-dependent evolution of the spectrum in greater detail, we model spectra for shorter exposures, confirming that most spectral parameters show either a gradual or sudden change for the second half of the second orbit. A comparison with a simple wind model indicates the existence of an accretion wake in this system. We also present and discuss high resolution pulse profiles for several different energy bands, as well as their hardness ratios. PCA and HEXTE spectra were created for 24 phase bins and fitted using the same model as in the phase averaged case. Systematic pulse phase-dependent variations of several continuum and cyclotron line parameters were detected, most notably a significant increase of the cyclotron line energy during the early rise of the main peak, followed by a gradual decrease. We show that applying a simple dipole model for the magnetic field is not sufficient to describe our data.Comment: 12 pages, 9 figures, accepted for publication in Ap

Extensive Mammalian Ancestry of Pandemic (H1N1) 2009 Virus

We demonstrate that the novel pandemic influenza (H1N1) viruses have human virus–like receptor specificity and can no longer replicate in aquatic waterfowl, their historic natural reservoir. The biological properties of these viruses are consistent with those of their phylogenetic progenitors, indicating longstanding adaptation to mammals

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk

Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort

INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls). RESULTS: We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00–2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02–2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88–1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37–0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women

Differential Carbohydrate Recognition by Campylobacter jejuni Strain 11168: Influences of Temperature and Growth Conditions

The pathogenic clinical strain NCTC11168 was the first Campylobacter jejuni strain to be sequenced and has been a widely used laboratory model for studying C. jejuni pathogenesis. However, continuous passaging of C. jejuni NCTC11168 has been shown to dramatically affect its colonisation potential. Glycan array analysis was performed on C. jejuni NCTC11168 using the frequently passaged, non-colonising, genome sequenced (11168-GS) and the infrequently passaged, original, virulent (11168-O) isolates grown or maintained under various conditions. Glycan structures recognised and bound by C. jejuni included terminal mannose, N-acetylneuraminic acid, galactose and fucose. Significantly, it was found that only when challenged with normal oxygen at room temperature did 11168-O consistently bind to sialic acid or terminal mannose structures, while 11168-GS bound these structures regardless of growth/maintenance conditions. Further, binding of un-capped galactose and fucosylated structures was significantly reduced when C. jejuni was maintained at 25°C under atmospheric oxygen conditions. These binding differences identified through glycan array analysis were confirmed by the ability of specific lectins to competitively inhibit the adherence of C. jejuni to a Caco-2 intestinal cell line. Our data suggests that the binding of mannose and/or N-acetylneuraminic acid may provide the initial interactions important for colonisation following environmental exposure

Gameplay as a source of intrinsic motivation in a randomized controlled trial of auditory training

Background: Previous studies of frequency discrimination training (FDT) for tinnitus used repetitive task-based training programmes relying on extrinsic factors to motivate participation. Studies reported limited improvement in tinnitus symptoms. Purpose: To evaluate FDT exploiting intrinsic motivations by integrating training with computer-gameplay. Methods: Sixty participants were randomly assigned to train on a conventional taskbased training, or one of two interactive game-based training platforms over six weeks. Outcomes included assessment of motivation, tinnitus handicap, and performance on tests of attention. Results: Participants reported greater intrinsic motivation to train on the interactive game-based platforms, yet compliance of all three groups was similar (~70%) and changes in self-reported tinnitus severity were not significant. There was no difference between groups in terms of change in tinnitus severity or performance on measures of attention. Conclusion: FDT can be integrated within an intrinsically motivating game. Whilst this may improve participant experience, in this instance it did not translate to additional compliance or therapeutic benefit

Labeled EF-Tus for rapid kinetic studies of pretranslocation complex formation

The universally conserved translation elongation factor EF-Tu delivers aminoacyl(aa)-tRNA in the form of an aa-tRNA·EF-Tu·GTP ternary complex (TC) to the ribosome where it binds to the cognate mRNA codon within the ribosomal A-site, leading to formation of a pretranslocation (PRE) complex. Here we describe preparation of QSY9 and Cy5 derivatives of the variant E348C-EF-Tu that are functional in translation elongation. Together with fluorophore derivatives of aa-tRNA and of ribosomal protein L11, located within the GTPase associated center (GAC), these labeled EF-Tus allow development of two new FRET assays that permit the dynamics of distance changes between EF-Tu and both L11 (Tu-L11 assay) and aa-tRNA (Tu-tRNA assay) to be determined during the decoding process. We use these assays to examine: (i) the relative rates of EF-Tu movement away from the GAC and from aa-tRNA during decoding, (ii) the effects of the misreading-inducing antibiotics streptomycin and paromomycin on tRNA selection at the A-site, and (iii) how strengthening the binding of aa-tRNA to EF-Tu affects the rate of EF-Tu movement away from L11 on the ribosome. These FRET assays have the potential to be adapted for high throughput screening of ribosomal antibiotics