Developing and applying heterogeneous phylogenetic models with XRate

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART .Comment: 34 pages, 3 figures, glossary of XRate model terminolog

Comparative expression of Cbf genes in the Triticeae under different acclimation induction temperatures

In plants, the C-repeat binding factors (Cbfs) are believed to regulate low-temperature (LT) tolerance. However, most functional studies of Cbfs have focused on characterizing expression after an LT shock and have not quantified differences associated with variable temperature induction or the rate of response to LT treatment. In the Triticeae, rye (Secale cereale L.) is one of the most LT-tolerant species, and is an excellent model to study and compare Cbf LT induction and expression profiles. Here, we report the isolation of rye Cbf genes (ScCbfs) and compare their expression levels in spring- and winter-habit rye cultivars and their orthologs in two winter-habit wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) cultivars. Eleven ScCbfs were isolated spanning all four major phylogenetic groups. Nine of the ScCbfs mapped to 5RL and one to chromosome 2R. Cbf expression levels were variable, with stronger expression in winter- versus spring-habit rye cultivars but no clear relationship with cultivar differences in LT, down-stream cold-regulated gene expression and Cbf expression were detected. Some Cbfs were expressed only at warmer acclimation temperatures in all three species and their expression was repressed at the end of an 8-h dark period at warmer temperatures, which may reflect a temperature-dependent, light-regulated diurnal response. Our work indicates that Cbf expression is regulated by complex genotype by time by induction–temperature interactions, emphasizing that sample timing, induction–temperature and light-related factors must receive greater consideration in future studies involving functional characterization of LT-induced genes in cereals

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

Emotional, behavioural problems and cigarette smoking in adolescence: findings of a Greek cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although several studies have reported findings concerning the association between smoking and emotional/behavioural problems, little research has investigated this association after controlling for confounding factors which have been found to be significantly correlated with both cigarette smoking and emotional/behavioural problems and may have a strong effect on the relationship between adolescents' mental health and smoking. The present study attempted to assess the association between adolescents' smoking status and their emotional/behavioural problems after controlling for a number of possible confounders (i.e. age, gender, parental smoking status, exposure to family smoking, family socioeconomic status, adolescents' leisure time) in a Greek nation-wide school-based sample.</p> <p>Methods</p> <p>Participants completed a questionnaire which retrieved information about age, gender, family socioeconomic status, smoking status, parental smoking, adolescents' leisure time and emotional/behavioural problems. Data were modelled using multiple logistic regression analysis with adolescents' smoking status as the dependent variable.</p> <p>Results</p> <p>A total of 1194 (i.e. 63% response rate) of self-reported questionnaires (40.1% boys, 59.9% girls; 12-18 years old) were returned. Data from 1030 participants with full data were analyzed. Cigarette smoking was strongly associated with higher levels of emotional/behavioural problems (p < 0.001) and the association was not moderated (OR = 1.13, 95% CI: 1.08-1.18) after controlling for the effects of other covariates. Emotional symptoms, conduct problems and hyperactivity/inattention were all significantly associated with adolescents' current smoking.</p> <p>Conclusions</p> <p>This study supports the association between smoking and emotional/behavioural problems among adolescents. Addressing adolescents' needs regarding their emotional/behavioural health could be helpful in the development of effective anti-smoking strategies in school environment and elsewhere.</p

Stellar winds from Massive Stars

We review the various techniques through which wind properties of massive stars - O stars, AB supergiants, Luminous Blue Variables (LBVs), Wolf-Rayet (WR) stars and cool supergiants - are derived. The wind momentum-luminosity relation (e.g. Kudritzki et al. 1999) provides a method of predicting mass-loss rates of O stars and blue supergiants which is superior to previous parameterizations. Assuming the theoretical sqrt(Z) metallicity dependence, Magellanic Cloud O star mass-loss rates are typically matched to within a factor of two for various calibrations. Stellar winds from LBVs are typically denser and slower than equivalent B supergiants, with exceptional mass-loss rates during giant eruptions Mdot=10^-3 .. 10^-1 Mo/yr (Drissen et al. 2001). Recent mass-loss rates for Galactic WR stars indicate a downward revision of 2-4 relative to previous calibrations due to clumping (e.g. Schmutz 1997), although evidence for a metallicity dependence remains inconclusive (Crowther 2000). Mass-loss properties of luminous (> 10^5 Lo) yellow and red supergiants from alternative techniques remain highly contradictory. Recent Galactic and LMC results for RSG reveal a large scatter such that typical mass-loss rates lie in the range 10^-6 .. 10^-4 Mo/yr, with a few cases exhibiting 10^-3 Mo/yr.Comment: 16 pages, 2 figures, Review paper to appear in Proc `The influence of binaries on stellar population studies', Brussels, Aug 2000 (D. Vanbeveren ed.), Kluwe

Successful Surgical Treatment of a Spontaneous Rupture of the Esophagus Diagnosed Two Days after Onset

Esophageal perforation is a relatively uncommon disease with a high rate of mortality and morbidity. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40–60%. Primary repair is generally considered the gold standard for patients who present within the first 24 h following perforation of the esophagus. In this paper, we present a case of successful surgical treatment of spontaneous rupture of the esophagus that was diagnosed 2 days after onset. The patient was a 42-year-old man admitted to internal medicine with a diagnosis of pleuritis and complaining of chest and back pain. The next day, computed tomography revealed left-sided pleural effusion and mediastinal emphysema. An esophagogram revealed extravasation of the contrast medium from the lower left esophagus to the mediastinal cavity. These results confirmed a rupture of the esophagus, and an emergency left thoracotomy was performed. The perforation was repaired with a single-layered closure and was covered with elevated great omentum obtained by laparotomy. The patient was discharged 23 days after the first surgery. In conclusion, primary repair surgery must be selected as the best treatment beyond 24 h if the patient's general state was stable and there was no evidence of clinical sepsis

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer

The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a potentially curative oesophagectomy for squamous or adenocarcinoma were reviewed retrospectively. As part of the procedure, all patients underwent an en-bloc resection of their periesophageal tissue. The presence of tumour either at, or within, 1 mm of the CRM was recorded and correlated with their TNM and survival data. A total of 67 patients (20%) were noted to have a positive CRM, of which 40 cases (12%) had tumour at the resection margin and the remainder had tumour within 1 mm of the margin. Univariate analysis showed no statistically significant association between survival and either category of CRM involvement. Multivariate analysis showed that only T-stage, nodal status and tumour grade were prognostic markers. In conclusion, the presence of microscopic tumour at the CRM following an en-bloc oesophagectomy is not a significant prognostic marker