Comparison of Mutation Patterns in Full-Genome A/H3N2 Influenza Sequences Obtained Directly from Clinical Samples and the Same Samples after a Single MDCK Passage

Human influenza viruses can be isolated efficiently from clinical samples using Madin-Darby canine kidney (MDCK) cells. However, this process is known to induce mutations in the virus as it adapts to this non-human cell-line. We performed a systematic study to record the pattern of MDCK-induced mutations observed across the whole influenza A/H3N2 genome. Seventy-seven clinical samples collected from 2009-2011 were included in the study. Two full influenza genomes were obtained for each sample: one from virus obtained directly from the clinical sample and one from the matching isolate cultured in MDCK cells. Comparison of the full-genome sequences obtained from each of these sources showed that 42% of the 77 isolates had acquired at least one MDCK-induced mutation. The presence or absence of these mutations was independent of viral load or sample origin (in-patients versus out-patients). Notably, all the five hemagglutinin missense mutations were observed at the hemaggutinin 1 domain only, particularly within or proximal to the receptor binding sites and antigenic site of the virus. Furthermore, 23% of the 77 isolates had undergone a MDCK-induced missense mutation, D151G/N, in the neuraminidase segment. This mutation has been found to be associated with reduced drug sensitivity towards the neuraminidase inhibitors and increased viral receptor binding efficiency to host cells. In contrast, none of the neuraminidase sequences obtained directly from the clinical samples contained the D151G/N mutation, suggesting that this mutation may be an indicator of MDCK culture-induced changes. These D151 mutations can confound the interpretation of the hemagglutination inhibition assay and neuraminidase inhibitor resistance results when these are based on MDCK isolates. Such isolates are currently in routine use in the WHO influenza vaccine and drug-resistance surveillance programs. Potential data interpretation miscalls can therefore be avoided by careful exclusion of such D151 mutants after further sequence analysis.published_or_final_versio

Update on HER-2 as a target for cancer therapy: The ERBB2 promoter and its exploitation for cancer treatment

Overexpression of the ERBB2 proto-oncogene is associated with amplification of the gene in breast cancer but increased activity of the promoter also plays a significant role. Members of two transcription factor families (AP-2 and Ets) show increased binding to the promoter in over-expressing cells. Consequently, strategies have been devised to target promoter activity, either through the DNA binding sites for these factors, or through another promoter sequence, a polypurine-polypyrimidine repeat structure. The promoter has also been exploited for its tumour-specific activity to direct the accumulation of cytotoxic compounds selectively within cancer cells. Our current understanding of the ERBB2 promoter is reviewed and the status of these therapeutic avenues is discussed

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Quark helicity distributions in the nucleon for up, down, and strange quarks from semi--inclusive deep--inelastic scattering

Polarized deep--inelastic scattering data on longitudinally polarized hydrogen and deuterium targets have been used to determine double spin asymmetries of cross sections. Inclusive and semi--inclusive asymmetries for the production of positive and negative pions from hydrogen were obtained in a re--analysis of previously published data. Inclusive and semi--inclusive asymmetries for the production of negative and positive pions and kaons were measured on a polarized deuterium target. The separate helicity densities for the up and down quarks and the anti--up, anti--down, and strange sea quarks were computed from these asymmetries in a ``leading order'' QCD analysis. The polarization of the up--quark is positive and that of the down--quark is negative. All extracted sea quark polarizations are consistent with zero, and the light quark sea helicity densities are flavor symmetric within the experimental uncertainties. First and second moments of the extracted quark helicity densities in the measured range are consistent with fits of inclusive data

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction

Evidence for a narrow baryon state is found in quasi-real photoproduction on a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1 (syst) MeV. Depending on the background model,the naive statistical significance of the peak is 4--6 standard deviations and its width may be somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s)) pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed in the pK^+ invariant mass distribution. The absence of such a signal indicates that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure

Prevalence of Cataract Surgery and Visual Outcomes in Indian Immigrants in Singapore: The Singapore Indian Eye Study

10.1371/journal.pone.0075584PLoS ONE810-POLN

Dead on arrival in a low-income country: results from a multicenter study in Pakistan

BACKGROUND: This study assessed the characteristics of dead on arrival (DOA) patients in Pakistan. METHODS: Data about the DOA patients were extracted from Pakistan National Emergency Department Surveillance study (Pak-NEDS). This study recruited all ED patients presenting to seven tertiary care hospitals during a four-month period between November 2010 and March 2011. This study included patients who were declared dead-on-arrival by the ED physician. RESULTS: A total of 1,557 DOA patients (7 per 1,000 visits) were included in the Pak-NEDS. Men accounted for two-thirds (64%) of DOA patients. Those aged 20-49 years accounted for about 46% of DOA patients. Nine percent (n = 72) of patients were brought by ambulance, and most patients presented at a public hospital (80%). About 11% of DOA patients had an injury. Factors significantly associated (p \u3c 0.05) with ambulance use were men (adjusted odds ratio [aOR] = 2.72), brought to a private hospital (OR = 2.74), and being injured (aOR = 1.89). Cardiopulmonary resuscitation (CPR) was performed on 6% (n = 42) of patients who received treatment. Those brought to a private hospital were more likely to receive CPR (aOR = 2.81). CONCLUSION: This study noted a higher burden of DOA patients in Pakistan compared to other resourceful settings (about 1 to 2 per 1,000 visits). A large proportion of patients belonging to productive age groups, and the low prevalence of ambulance and CPR use, indicate a need for improving the prehospital care and basic life support training in pakistan

Illegal immigration and media exposure: evidence on individual attitudes

Illegal immigration has been the focus of much debate in receiving countries, but little is known about the drivers of individual attitudes towards illegal immigrants. To study this question, we use the CCES survey, which was carried out in 2006 in the USA. We find evidence that—in addition to standard labor market and welfare state considerations—media exposure is significantly correlated with public opinion on illegal immigration. Controlling for education, income, ideology, and other socio-demographic characteristics, individuals watching Fox News are 9 percentage points more likely than CBS viewers to oppose the legalization of undocumented immigrants. We find an effect of the same size and direction for CNN viewers, whereas individuals watching PBS are instead more likely to support legalization. Ideological self-selection into different news programs plays an important role, but cannot entirely explain the correlation between media exposure and attitudes about illegal immigration