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  • 1
    Publication Date: 2016-08-20
    Description: To improve the epigenomic analysis of tissues rich in 5-hydroxymethylcytosine (hmC), we developed a novel protocol called TAB-Methyl-SEQ, which allows for single base resolution profiling of both hmC and 5-methylcytosine by targeted next-generation sequencing. TAB-Methyl-SEQ data were extensively validated by a set of five methodologically different protocols. Importantly, these extensive cross-comparisons revealed that protocols based on Tet1-assisted bisulfite conversion provided more precise hmC values than TrueMethyl-based methods. A total of 109 454 CpG sites were analyzed by TAB-Methyl-SEQ for mC and hmC in 188 genes from 20 different adult human livers. We describe three types of variability of hepatic hmC profiles: (i) sample-specific variability at 40.8% of CpG sites analyzed, where the local hmC values correlate to the global hmC content of livers (measured by LC-MS), (ii) gene-specific variability, where hmC levels in the coding regions positively correlate to expression of the respective gene and (iii) site-specific variability, where prominent hmC peaks span only 1 to 3 neighboring CpG sites. Our data suggest that both the gene- and site-specific components of hmC variability might contribute to the epigenetic control of hepatic genes. The protocol described here should be useful for targeted DNA analysis in a variety of applications.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Franklin, C -- Seebacher, F -- Grigg, G C -- Axelsson, M -- New York, N.Y. -- Science. 2000 Sep 8;289(5485):1687-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11001731" target="_blank"〉PubMed〈/a〉
    Keywords: Alligators and Crocodiles/*anatomy & histology/*physiology ; Animals ; Basal Metabolism ; Heart/*anatomy & histology/*physiology ; *Hemodynamics ; Oxygen/blood ; Pulmonary Circulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of fish biology 60 (2002), S. 0 
    ISSN: 1095-8649
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The maximum values for heart rate (fH), stroke volume (VH), cardiac output (Q) and myocardial power output, measured in vitro with a perfused heart preparation, as well as the isometric force-frequency relationship for atrial and ventricular muscle strips, in triploid brown trout Salmo trutta were all comparable with established information for diploid rainbow trout Oncorhynchus mykiss. Therefore, it was concluded that triploidy is not associated with a major deficiency in maximum cardiac performance. However, a heightened sensitivity to ryanodine was discovered, which indicated an enhanced role for the sarcoplasmic reticulum in excitation-contraction coupling in these triploid fish. It is suspected that the enhanced role of the ryanodine receptor may be a cellular compensation related to larger cardiac myocytes. It was also clearly established that there was a plateau in maximum cardiac performance between 14 and 18° C and this plateau might be a contributing factor to the reduced factorial aerobic scope and increased fish mortality observed at 18° C.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-136X
    Keywords: Key words Gastrointestinal blood flow ; Feeding ; Adrenaline ; α-Adrenoceptors ; Teleost
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Cardiac output, blood flow to the coeliac and mesenteric arteries, dorsal aortic blood pressure and heart rate were recorded simultaneously at rest and postprandial for 6 days in a teleost, the red Irish lord (Hemilepidotus hemilepidotus). We anticipated that gastrointestinal blood flow would increase postprandially, supported by an increase in cardiac output. However, we had no predictions for either the exact time-course of this response, or for the regional distribution of blood flow between to the two major arteries comprising the splanchnic circulation. In resting, unfed animals, blood flow to the coeliac artery and mesenteric artery was 4.1 ± 0.6 ml min−1 kg−1 and 4.9 ± 1.3 ml min−1 kg−1, respectively (mean ± SEM, n=7), which together represented 34% of cardiac output. Feeding increased blood flow to the coeliac and mesenteric arteries in a time-dependent manner. The increase in coeliac artery blood flow preceded that in the mesenteric artery, a finding that is consistent with the coeliac artery supplying blood to the liver and stomach, while the mesenteric artery supplies blood to the stomach and intestine. Coeliac blood flow had increased by 84 ± 18% after 1 day and had a peak increase of 112 ± 40% at day 4 postprandial. Mesenteric blood flow was not significantly elevated at day 1, but had increased by 94 ± 19% at day 4 postprandial. Cardiac output also increased progressively, increasing by a maximum of 90 ± 30% at day 4. Because the increase in cardiac output was adequate to meet the postprandial increase in gut blood flow, the postprandial decreases in vascular resistance for the coeliac and mesenteric circulations mirrored the increases in blood flow. Intra-arterial injections of adrenaline and noradrenaline into resting fish more than doubled coeliac and mesenteric vascular resistances, and blood flow decreased proportionately. This adrenergic vasoconstriction was totally abolished by pretreatment with the α-adrenoceptor antagonist phentolamine, which in itself approximately halved coeliac and mesenteric vascular resistances. These observations indicate a significant α-adrenergic tone in the gastrointestinal circulation of the red Irish lord, the loss of which could not entirely account for the postprandial increase in gastrointestinal blood flow. Other control mechanisms are suggested.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2016-07-13
    Description: Accreting stellar-mass black holes often show a ‘Type-C’ quasi-periodic oscillation (QPO) in their X-ray flux and an iron emission line in their X-ray spectrum. The iron line is generated through continuum photons reflecting off the accretion disc, and its shape is distorted by relativistic motion of the orbiting plasma and the gravitational pull of the black hole. The physical origin of the QPO has long been debated, but is often attributed to Lense–Thirring precession, a General Relativistic effect causing the inner flow to precess as the spinning black hole twists up the surrounding space–time. This predicts a characteristic rocking of the iron line between red- and blueshift as the receding and approaching sides of the disc are respectively illuminated. Here we report on XMM–Newton and NuSTAR observations of the black hole binary H1743–322 in which the line energy varies systematically over the ~4 s QPO cycle (3.70 significance), as predicted. This provides strong evidence that the QPO is produced by Lense–Thirring precession, constituting the first detection of this effect in the strong gravitation regime. There are however elements of our results harder to explain, with one section of data behaving differently than all the others. Our result enables the future application of tomographic techniques to map the inner regions of black hole accretion discs.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 6
    Publication Date: 2015-04-30
    Description: Much evidence points towards that the photosphere in the relativistic outflow in GRBs plays an important role in shaping the observed MeV spectrum. However, it is unclear whether the spectrum is fully produced by the photosphere or whether a substantial part of the spectrum is added by processes far above the photosphere. Here we make a detailed study of the -ray emission from single pulse GRB110920A which has a spectrum that becomes extremely narrow towards the end of the burst. We show that the emission can be interpreted as Comptonization of thermal photons by cold electrons in an unmagnetized outflow at an optical depth of  ~ 20. The electrons receive their energy by a local dissipation occurring close to the saturation radius. The main spectral component of GRB110920A and its evolution is thus, in this interpretation, fully explained by the emission from the photosphere including localized dissipation at high optical depths.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 7
    Publication Date: 2015-01-16
    Description: The emission processes active in the highly relativistic jets of gamma-ray bursts (GRBs) remain unknown. In this paper, we propose a new measure to describe spectra: the width of the EF E spectrum, a quantity dependent only on finding a good fit to the data. We apply this to the full sample of GRBs observed by Fermi /Gamma-ray Burst Monitor (GBM) and Compton Gamma-ray Observatory /Burst and Transient Source Experiment (BATSE). The results from the two instruments are fully consistent. We find that the median widths of spectra from long and short GRBs are significantly different (chance probability 〈10 –6 ). The width does not correlate with either duration or hardness, and this is thus a new, independent distinction between the two classes. Comparing the measured spectra with widths of spectra from fundamental emission processes – synchrotron and blackbody radiation – the results indicate that a large fraction of GRB spectra are too narrow to be explained by synchrotron radiation from a distribution of electron energies: for example, 78 per cent of long GRBs and 85 per cent of short GRBs are incompatible with the minimum width of standard slow cooling synchrotron emission from a Maxwellian distribution of electrons, with fast cooling spectra predicting even wider spectra. Photospheric emission can explain the spectra if mechanisms are invoked to give a spectrum much broader than a blackbody.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 8
    Publication Date: 2016-03-18
    Description: One of the major results from the study of gamma-ray bursts with the Fermi Gamma-ray Space Telescope has been the confirmation that several emission components can be present in the energy spectrum. Here, we reanalyse the spectrum of GRB 080825C using data from the Fermi -Large Area Telescope (LAT) and Gamma-ray Burst Monitor instruments. Although fairly weak, it is the first gamma-ray burst detected by the Fermi -LAT. We improve on the original analysis by using the LAT Low Energy events covering the 30–100 MeV band. We find evidence of an additional component above the main emission peak (modelled using a Band function) with a significance of 3.5 in two out of the four time bins. The component is well fitted by a Planck function, but shows unusual behaviour: the peak energy increases in the prompt emission phase, reaching energies of several MeV. This is the first time such a trend has been seen, and implies that the origin of this component is different from those previously detected. We suggest that the two spectral components likely arise in different regions of the outflow, and that strong constraints can be achieved by assuming one of them originates from the photosphere. The most promising model appears to be that the high-energy peak is the result of photospheric emission in a Poynting flux dominated outflow where the magnetization increases with time.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 9
    Publication Date: 2016-03-18
    Description: We use frequency-resolved spectroscopy to examine the energy spectra of the prominent low-frequency quasi-periodic oscillation (QPO) and its harmonic in GX 339-4. We track the evolution of these spectra as the source makes a transition from a bright low/hard to hard intermediate state. In the hard/intermediate states, the QPO and time-averaged spectra are similar and the harmonic is either undetected or similar to the QPO. By contrast, in the softer states, the harmonic is dramatically softer than the QPO spectrum and the time-averaged spectrum, and the QPO spectrum is dramatically harder than the time-averaged spectrum. Clearly, the existence of these very different spectral shaped components mean that the time-averaged spectra are complex, as also seen by the fact that the softer spectra cannot be well described by a disc, Comptonization and its reflection. We use the frequency-resolved spectra to better constrain the model components, and find that the data are consistent with a time-averaged spectrum which has an additional low-temperature, optically thick Comptonization component. The harmonic can be described by this additional component alone, while the QPO spectrum is similar to that of the hard Comptonization and its reflection. Neither QPO nor harmonic shows signs of the disc component even when it is strong in the time-averaged spectrum. This adds to the growing evidence for inhomogeneous Comptonization in black hole binaries. While the similarity between the harmonic and QPO spectra in the intermediate state can be produced from the angular dependence of Compton scattering in a single region, this cannot explain the dramatic differences seen in the soft state. Instead, we propose that the soft Compton region is located predominantly above the disc while the hard Compton is from the hotter inner flow. Our results therefore point to multiple possible mechanisms for producing harmonic features in the power spectrum. The dominant mechanism in a given observation is likely a function of both inclination angle and inner disc radius.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 10
    Publication Date: 2015-06-01
    Print ISSN: 0004-6361
    Electronic ISSN: 1432-0746
    Topics: Physics
    Published by EDP Sciences
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