Ensembl 2009.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Ensembl 2006.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes.

BACKGROUND: Ventilation-perfusion (VQ) scanning is used when pulmonary embolism (PE) is suspected during pregnancy; however, the distribution of lung scan results and safety of VQ scanning have never been studied. OBJECTIVE: To study the distribution of lung scan results and safety of VQ scanning as well as the safety of withholding anticoagulation therapy following a normal or nondiagnostic scan in pregnant women. METHODS: The study group comprised 120 consecutive pregnant women who presented with suspected PE. Clinical data were collected, and the lung scans were reinterpreted by 2 independent experts. Subsequent pregnancy and pediatric outcomes were determined by direct patient follow-up. RESULTS: During the study period, 120 pregnant women (mean age, 32 years) underwent 121 VQ scans. Eight cases (6.6%) were already receiving treatment for venous thromboembolism prior to VQ scanning. In the remaining 113 scans, 83 (73.5%) were interpreted as normal, 28 (24.8%) as nondiagnostic, and 2 (1.8%) as high probability. In the 104 women who did not receive anticoagulation therapy following lung scanning (80 normal and 24 nondiagnostic), no venous thromboembolic events were reported (mean [range] length of follow-up, 20.6 [0.5-108] months). Examination of pediatric data from 110 live births (90.2%) (mean [range] age, 20.5 [0.5-100] months) revealed no increase in the rates of congenital and developmental anomalies. CONCLUSIONS: The prevalence of high-probability VQ scans in pregnant women with suspected PE and probable PE is very low. Withholding anticoagulation in pregnant women with normal or nondiagnostic VQ scans is probably safe. In addition, pediatric risks from VQ scans are low. Large prospective studies are needed to evaluate diagnostic strategies for pregnant women with suspected PE.

Selection of patients for resection of hepatic metastases: improved detection of extrahepatic disease with FDG pet.

A rapidly emerging clinical application of positron emission tomography (PET) is the detection of tumor tissue at whole-body studies performed with the glucose analogue 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). High rates of recurrence after partial hepatic resection in patients with colorectal cancer liver metastases indicate that current presurgical imaging strategies are failing to show extrahepatic tumor deposits. Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in the liver and the lungs, it is particularly useful for identification and characterization of extrahepatic disease. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterization of indeterminate soft-tissue masses. Several sources of benign and physiologic increased activity at FDG PET emphasize the need for careful correlation with findings of other imaging studies and clinical findings. FDG PET can improve the selection of patients for partial hepatic resection and thereby reduce the morbidity and mortality associated with inappropriate surgery.

Single-site beta-diiminate zinc catalysts for the alternating copolymerization of CO2 and epoxides: catalyst synthesis and unprecedented polymerization activity.

Synthetic routes to zinc beta-diiminate complexes are reported. The synthesis of 11 beta-diimine [(BDI)-H] ligands, with varying N-aryl substituents and bridging structures, is described. These ligands are converted to (BDI)ZnX complexes (X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr). X-ray structural data revealed that all zinc complexes examined exist as micro-X-bridged dimers in the solid state, with the exception of the zinc ethyl and amido complexes which were monomeric. Complexes of the form (BDI)ZnOR (R = alkyl, acyl) and (BDI)ZnN(SiMe3)2 are highly active catalysts for the alternating copolymerization of epoxides and CO2. Copolymerizations of cyclohexene oxide (CHO) and CO2 with (BDI-1)ZnX [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene)] and (BDI-2)ZnX [(BDI-2) = 2-((2,6-diethylphenyl)amido)-4-((2,6-diethylphenyl)imino)-2-pentene)], where X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr, were attempted at 50 degrees C and 100 psi CO2. Complexes with X = OAc, N(SiMe3)2, OMe, O(i)Pr all produced polycarbonate by the alternated insertion of CHO and CO2 with similar catalytic activities, comparable molecular weights, and narrow molecular weight distributions (MWD approximately 1.1), indicating the copolymerizations are living. Furthermore, ligand effects were shown to dramatically influence the polymerization activity as minor steric changes accelerated or terminated the polymerization activity.

Visual and semiquantitative analysis of 18F-fluorodeoxyglucose positron emission tomography using a partial-ring tomograph without attenuation correction to differentiate benign and malignant pulmonary nodules.

OBJECTIVE: Many studies have reported the use of attenuation-corrected positron emission tomography with 18F-fluorodeoxyglucose (FDG PET) with full-ring tomographs to differentiate between benign and malignant pulmonary nodules. We sought to evaluate FDG PET using a partial-ring tomograph without attenuation correction. METHODS: A retrospective review of PET images from 77 patients (range 38-84 years of age) with proven benign or malignant pulmonary nodules was undertaken. All images were obtained using a Siemens/CTI ECAT ART tomograph, without attenuation correction, after 185 MBq 18F-FDG was injected. Images were visually graded on a 5-point scale from "definitely malignant" to "definitely benign," and lesion-to-background (LB) ratios were calculated using region of interest analysis. Visual and semiquantitative analyses were compared using receiver operating characteristic analysis. RESULTS: Twenty lesions were benign and 57 were malignant. The mean LB ratio for benign lesions was 1.5 (range 1.0-5.7) and for malignant lesions 5.7 (range 1.2-14.1) (p < 0.001). The area under the ROC curve for LB ratio analysis was 0.95, and for visual analysis 0.91 (p = 0.39). The optimal cut-off ratio with LB ratio analysis was 1.8, giving a sensitivity of 95% and a specificity of 85%. For lesions thought to be "definitely malignant" on visual analysis, the sensitivity was 93% and the specificity 85%. Three proven infective lesions were rated as malignant by both techniques (LB ratio 2.6-5.7). CONCLUSIONS: FDG PET without attenuation correction is accurate for differentiating between benign and malignant lung nodules. Results using simple LB ratios without attenuation correction compare favourably with the published sensitivity and specificity for standard uptake ratios. Visual analysis is equally accurate.

Polymerization of lactide with zinc and magnesium beta-diiminate complexes: stereocontrol and mechanism.

A series of zinc(II) and magnesium(II) alkoxides based upon a beta-diiminate ligand framework has been prepared. [(BDI-1)ZnO(i)Pr](2) [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene] exhibited the highest activity and stereoselectivity of the zinc complexes studied for the polymerization of rac- and meso-lactide to poly(lactic acid) (PLA). [(BDI-1)ZnO(i)()Pr](2) polymerized (S,S)-lactide to isotactic PLA without epimerization of the monomer, rac-lactide to heterotactic PLA (P(r) = 0.94 at 0 degrees C), and meso-lactide to syndiotactic PLA (P(r) = 0.76 at 0 degrees C). The polymerizations are living, as evidenced by the narrow polydispersities of the isolated polymers in addition to the linear nature of number average molecular weight versus conversion plots and monomer-to-catalyst ratios. The substituents on the beta-diiminate ligand exert a significant influence upon the course of the polymerizations, affecting both the degree of stereoselectivity and the rate of polymerization. Kinetic studies with [(BDI-1)ZnO(i)Pr](2) indicate that the polymerizations are first order with respect to monomer (rac-lactide) and 1.56 order in catalyst. Polymerization experiments with [(BDI-1)MgO(i)Pr](2) revealed that this complex is extremely fast for the polymerization of rac-lactide, polymerizing 500 equiv in 96% yield in less than 5 min at 20 degrees C.

High-performance liquid chromatography for the characterization of carotenoids in the new sweet orange (Earlygold) grown in Florida, USA.

High-performance liquid chromatography with photodiode array detection was developed for the separation and identification of carotenoids from a new sweet orange, Earlygold. Carotenoid pigments were extracted using hexane-acetone-ethanol and saponified using 10% methanolic potassium hydroxide. More than 25 carotenoid pigments were separated within 40 min using a ternary gradient (acetonitrile-methanol, methyl tert-butyl ether and water) elution on a C30 reversed-phase column. The carotenoid pattern of Earlygold was generally similar to the early season Hamlin but with some quantitative differences, especially with violaxanthin. Major carotenoids including violaxanthin, lutein, beta-cryptoxanthin, antheraxanthin, luteoxanthin, zeaxanthin, beta-carotene, and alpha-carotene were identified based on on-line spectral data obtained by a photodiode array detector, and comparison to the spectra of the standards and reported values. A numerical notation, the ratio of the peak heights between absorption bands, was also calculated to compare to the literature values.

The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study.

BACKGROUND: The mechanism for the beneficial effect of beta-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVO(2)). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. METHODS AND RESULTS: The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressure x SVI x heart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061+/-0.022 to 0.054+/-0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062+/-0. 024 to 0.045+/-0.015 per minute; P:=0.002). The work-metabolic index did not change with placebo (from 5.29+/-2.46 x 10(6) to 5.14+/-2. 06 x 10(6) mm Hg. mL/m(2)), but it increased with metoprolol (from 5. 31+/-2.15 x 10(6) to 7.08+/-2.36 x 10(6) mm Hg. mL/m(2); P:<0.001). CONCLUSIONS: Selective beta-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with beta-blocker therapy in this patient population.

Imaging features of primary and recurrent esophageal cancer at FDG PET.

Because of the poor prognosis for patients with esophageal cancer and the risks associated with surgical intervention, accurate staging is essential for optimal treatment planning. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) is a useful adjunct to more conventional imaging modalities in this setting. FDG PET is not an appropriate first-line diagnostic procedure in the detection of esophageal cancer and is not helpful in detecting local invasion by the primary tumor, and further studies are required to determine its efficacy in the detection of local nodal metastases. However, FDG PET is superior to anatomic imaging modalities in the ability to detect distant metastases. Metastases to the liver, lungs, and skeleton can readily be identified at FDG PET. In addition, FDG PET has proved valuable in determining the resectability of disease and allows scanning of a larger volume than is possible with computed tomography. Recurrent disease is readily diagnosed and differentiated from scar tissue with FDG PET. In addition, FDG PET may play a valuable role in the follow-up of patients who undergo chemotherapy and radiation therapy, allowing early changes in treatment for unresponsive tumors. The management of most patients with esophageal cancer can be improved with use of FDG PET.

FDG PET of recurrent or metastatic 131I-negative papillary thyroid carcinoma.

UNLABELLED: This study reports on the use of FDG PET in the follow-up of papillary thyroid cancer patients with negative findings on 131I total body scans and elevated levels of thyroglobulin after total thyroidectomy. METHODS: Eleven asymptomatic patients with previous papillary thyroid cancer, total thyroidectomy, 131I ablation, and treatment of all known metastases had negative findings on 131I total body scans after therapy but persisting elevations of thyroglobulin when not receiving thyroid hormone. All imaging before PET failed to show persisting tumor. FDG PET was performed on all patients while receiving full thyroid hormone replacement, except for the repeated scan of 1 patient (patient 6). After the PET scan, all patients were referred for supplementary CT, sonography, or biopsy of lesions in the neck. RESULTS: All 11 patients showed FDG uptake in the neck or upper mediastinum-in the initial scan in 10 and in a repeated scan in 1. Sonographically guided biopsy confirmed malignancy in 6, was nondiagnostic in 2, and showed normal findings in 1. In 2 patients, the sonographic results were normal and no biopsy was attempted. FDG imaging redirected the treatment of 7 patients, resulting in surgery and external beam radiotherapy in 3, surgery in 1, and external beam radiotherapy in 2. One patient declined further recommended surgery. The other 4 patients remain under observation. Surgical histopathology confirmed thyroid tumor in all 4 surgically treated patients. Retrospective review of the original histopathology slides showed no preponderance of aggressive histology. CONCLUSION: FDG PET is able to guide further evaluation of thyroid cancer patients who have elevated thyroglobulin levels and normal findings on 131I whole-body scanning.

Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying in a multicenter setting.

OBJECTIVE: Scintigraphy remains the gold standard to study gastric emptying. The technique is onerous and normal values vary between centers. Standardized protocols, although desirable, are not presently available. We validated a simplified scintigraphic protocol in a multicenter setting. METHODS: In 69 healthy volunteers from seven Canadian institutions, gastric emptying of a standard meal (99mTc-labeled beef liver) was assessed by scintigraphy every 10 min for 1 h, then every 20 min for the next 2 h. Gastric retention was fitted to a power exponential model, Prop(t) = (-(kappat)beta) with Prop(t) = proportion of retention at time t, either using all 13 time intervals (conventional technique) or using measurements at 0, 1, 2, and 3 h (simplified technique). RESULTS: The power exponential model yielded identical emptying curves and T 1/2 values with both techniques. Gastric emptying was more rapid in men than in women < 35 yr (p<0.01) and in younger than in older men (p<0.005). Gastric emptying was slower in women from Québec than in women from Ontario (p<0.04). Gastric retention was similar at 1, 2, and 3 h among the seven centers. Gastric emptying of a beef liver meal was slower than that of a low fat egg substitute (p<0.03). CONCLUSIONS: A simpler scintigraphic approach, using four rather than 13 samples, provides results comparable to those of the conventional technique. This simpler approach provides an economical, yet accurate, alternative to the techniques presently used and is applicable to a multicenter setting.

Estimation of pulmonary deposition of aerosol using gamma scintigraphy.

Following delivery of technetium 99m-labeled aerosols through a ventilator circuit, the amount of radioactivity in the lungs of 58 ventilated rabbits was estimated first by gamma scintigraphy via gamma camera and later by direct counting of the excised lungs (n = 116 specimens) with a gamma counter. The in situ radioactivity measured via scintigraphy was closely correlated with the gamma counter ex vivo tissue counts of the radioactivity (R2 = 0.997, P < 0.001). Overall, gamma scintigraphy gave slightly lower values of activity than the tissue counts from the gamma counter, but the limits of agreement between the two measurements were narrow enough for us to consider that the tissue and scintigraphy methods were in agreement. We conclude that gamma scintigraphy provides a convenient and noninvasive means for the accurate estimation of aerosol deposition in the lungs of small animals and possibly in small infants.

Emerging role of PET in the diagnosis and staging of lung cancer.

Positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG) has recently emerged as a practical and useful imaging modality in patients with lung cancer. Malignant tumours demonstrate increased uptake of FDG, a positron-emitting radiopharmaceutical. This increased FDG uptake in tumours can be seen using PET. FDG PET has much higher accuracy than other imaging modalities for the differentiation of benign and malignant lung nodules. The sensitivity of PET is 96% and the specificity 77% for diagnosing malignant nodules. PET is also more accurate than computed tomography (CT) for staging mediastinal nodal involvement (sensitivity 89%, specificity 94%). While CT relies on an arbitrary anatomical cutoff of 1 cm to diagnose malignant nodes, which may simply be enlarged due to inflammation, PET can accurately diagnose metastases in nodes smaller than 1 cm. Several studies have shown significantly better staging of distant metastases with FDG PET than with traditional techniques such as bone scanning. Differentiation of recurrent disease from scar tissue in the postoperative patient is often difficult with CT or magnetic resonance imaging. The low uptake of FDG in scar tissue allows reliable differentiation between scar tissue and a recurring tumour with PET. Early studies suggest a promising role for PET in the evaluation of response to chemotherapy. This may allow treatment to be changed after only one course of chemotherapy, instead of waiting for anatomical disease progression to become obvious clinically or with CT. Finally, significant improvements in cost effectiveness have been demonstrated when FDG PET is added to the preoperative work-up of patients with lung cancer.