| 1. |
- Medema, M. H., et al.
(författare)
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Minimum Information about a Biosynthetic Gene cluster
- 2015
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 11:9, s. 625-631
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Forskningsöversikt (refereegranskat)abstract
- A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
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| 2. |
- Shameer, S., et al.
(författare)
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TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:D1, s. D637-D644
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Tidskriftsartikel (refereegranskat)abstract
- The metabolic network of a cell represents thecatabolic and anabolic reactions that interconvertsmall molecules (metabolites) through the activity ofenzymes, transporters and non-catalyzed chemicalreactions. Our understanding of individual metabolicnetworks is increasing as we learn more aboutthe enzymes that are active in particular cells underparticular conditions and as technologies advanceto allow detailed measurements of the cellularmetabolome. Metabolic network databases areof increasing importance in allowing us to contextualisedata sets emerging from transcriptomic,proteomic and metabolomic experiments. Here wepresent a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describesthe generic and condition-specific metabolic networkof Trypanosoma brucei, a parasitic protozoan responsiblefor human and animal African trypanosomiasis.In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have alsoimplemented a network-based representation of theinformation through MetExplore, yielding a novel environmentin which to visualise the metabolism ofthis important parasite.
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| 3. |
- Heald, G. H., et al.
(författare)
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The LOFAR Multifrequency Snapshot Sky Survey (MSSS) : I. Survey description and first results
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- We present the Multifrequency Snapshot Sky Survey (MSSS), the first northern-sky Low Frequency Array (LOFAR) imaging survey. In this introductory paper, we first describe in detail the motivation and design of the survey. Compared to previous radio surveys, MSSS is exceptional due to its intrinsic multifrequency nature providing information about the spectral properties of the detected sources over more than two octaves (from 30 to 160 MHz). The broadband frequency coverage, together with the fast survey speed generated by LOFAR’s multibeaming capabilities, make MSSS the first survey of the sort anticipated to be carried out with the forthcoming Square Kilometre Array (SKA). Two of the sixteen frequency bands included in the survey were chosen to exactly overlap the frequency coverage of large-area Very Large Array (VLA) and Giant Metrewave Radio Telescope (GMRT) surveys at 74 MHz and 151 MHz respectively. The survey performance is illustrated within the MSSS Verification Field (MVF), a region of 100 square degrees centered at (α,δ)J2000 = (15h,69°). The MSSS results from the MVF are compared with previous radio survey catalogs. We assess the flux and astrometric uncertainties in the catalog, as well as the completeness and reliability considering our source finding strategy. We determine the 90% completeness levels within the MVF to be 100 mJy at 135 MHz with 108″ resolution, and 550 mJy at 50 MHz with 166″ resolution. Images and catalogs for the full survey, expected to contain 150 000–200 000 sources, will be released to a public web server. We outline the plans for the ongoing production of the final survey products, and the ultimate public release of images and source catalogs.
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| 4. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 5. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 6. |
- Coenen, T., et al.
(författare)
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The LOFAR pilot surveys for pulsars and fast radio transients
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- We have conducted two pilot surveys for radio pulsars and fast transients with the Low-Frequency Array (LOFAR) around 140 MHz and here report on the first low-frequency fast-radio burst limit and the discovery of two new pulsars. The first survey, the LOFAR Pilot Pulsar Survey (LPPS), observed a large fraction of the northern sky, ~ 1.4 × 104 deg2, with 1 h dwell times. Each observation covered ~75 deg2 using 7 independent fields formed by incoherently summing the high-band antenna fields. The second pilot survey, the LOFAR Tied-Array Survey (LOTAS), spanned ~600 deg2, with roughly a 5-fold increase in sensitivity compared with LPPS. Using a coherent sum of the 6 LOFAR “Superterp” stations, we formed 19 tied-array beams, together covering 4 deg2 per pointing. From LPPS we derive a limit on the occurrence, at 142 MHz, of dispersed radio bursts of < 150 day-1 sky-1, for bursts brighter than S> 107 Jy for the narrowest searched burst duration of 0.66 ms. In LPPS, we re-detected 65 previously known pulsars. LOTAS discovered two pulsars, the first with LOFAR or any digital aperture array. LOTAS also re-detected 27 previously known pulsars. These pilot studies show that LOFAR can efficiently carry out all-sky surveys for pulsars and fast transients, and they set the stage for further surveying efforts using LOFAR and the planned low-frequency component of the Square Kilometer Array.
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| 7. |
- Hassall, T. E., et al.
(författare)
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Differential frequency-dependent delay from the pulsar magnetosphere
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552
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Tidskriftsartikel (refereegranskat)abstract
- Some radio pulsars show clear "drifting subpulses", in which subpulses are seen to drift in pulse longitude in a systematic pattern. Here we examine how the drifting subpulses of PSR B0809+74 evolve with time and observing frequency. We show that the subpulse period (P-3) is constant on timescales of days, months and years, and between 14-5100 MHz. Despite this, the shapes of the driftbands change radically with frequency. Previous studies have concluded that, while the subpulses appear to move through the pulse window approximately linearly at low frequencies ( 820 MHz) near to the peak of the average pulse profile. We use LOFAR, GMRT, GBT, WSRT and Effelsberg 100-m data to explore the frequency-dependence of this phase step. We show that the size of the subpulse phase step increases gradually, and is observable even at low frequencies. We attribute the subpulse phase step to the presence of two separate driftbands, whose relative arrival times vary with frequency - one driftband arriving 30 pulses earlier at 20 MHz than it does at 1380 MHz, whilst the other arrives simultaneously at all frequencies. The drifting pattern which is observed here cannot be explained by either the rotating carousel model or the surface oscillation model, and could provide new insight into the physical processes happening within the pulsar magnetosphere.
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| 8. |
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| 9. |
- Holmes, Michael V., et al.
(författare)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 10. |
- Jelic, V., et al.
(författare)
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Initial LOFAR observations of epoch of reionization windows II. Diffuse polarized emission in the ELAIS-N1 field
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568, s. A101-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. This study aims to characterise the polarized foreground emission in the ELAIS-N1 field and to address its possible implications or extracting of the cosmological 21 cm signal from the LOw-Frequency ARray - Epoch of Reionization (LOFAR-EoR) data Methods. We used the high band antennas of LOFAR to image this region and RM-synthesis to unravel structures of polarized emission at high Galactic latitudes. Results. The brightness temperature of the detected Galactic emission is on average similar to 4 K in polarized intensity and covers the range from -10 to +13 rad m(-2) in Faraday depth, The total polarized intensity and polarization angle show a wide range of morphological features. We have also used the Westerbork Synthesis Radio Telescope (WSRT) at 350 MHz to image the same region. The LOFAR and WSRT images show a similar complex morphology at comparable brightness levels, but their spatial correlation is very low. The fractional polarization at 150 MHz, expressed as a percentage of the total intensity, amounts to approximate to 1.5%. There is no indication of diffuse emission in total intensity in the interferometric data. in line with results at higher frequencies Conclusions. The wide frequency range. high angular resolution, and high sensitivity make LOFAR an exquisite instrument for studying Galactic polarized emission at a resolution of similar to 1-2 rad m(-2) in Faraday depth. The different polarized patterns observed at 150 MHz and 350 MHz are consistent with different source distributions along the line of sight wring in a variety of Faraday thin regions of emission. The presence of polarized foregrounds is a serious complication for epoch of reionization experiments. To avoid the leakage of polarized emission into total intensity, which can depend on frequency, we need to calibrate the instrumental polarization across the field of view to a small fraction of 1%.
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