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1.
  • Feroci, M., et al. (författare)
  • The large observatory for x-ray timing
  • 2014
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
  • Konferensbidrag (refereegranskat)abstract
    • The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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2.
  • Feroci, M., et al. (författare)
  • LOFT - The large observatory for x-ray timing
  • 2012
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
  • Konferensbidrag (refereegranskat)abstract
    • The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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3.
  • Suzuki, N., et al. (författare)
  • THE HUBBLE SPACE TELESCOPE CLUSTER SUPERNOVA SURVEY. V. IMPROVING THE DARK- ENERGY CONSTRAINTS ABOVE z > 1 AND BUILDING AN EARLY-TYPE-HOSTED SUPERNOVA SAMPLE
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Advanced Camera for Surveys, NICMOS, and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 < z < 1.415. Of these SNe Ia, 14 pass our strict selection cuts and are used in combination with the world's sample of SNe Ia to derive the best current constraints on dark energy. Of our new SNe Ia, 10 are beyond redshift z = 1, thereby nearly doubling the statistical weight of HST-discovered SNe Ia beyond this redshift. Our detailed analysis corrects for the recently identified correlation between SN Ia luminosity and host galaxy mass and corrects the NICMOS zero point at the count rates appropriate for very distant SNe Ia. Adding these SNe improves the best combined constraint on dark-energy density,rho(DE)(z), at redshifts 1.0 < z < 1.6 by 18% (including systematic errors). For a flat. CDM universe, we find Omega(A) = 0.729 +/- 0.014 (68% confidence level (CL) including systematic errors). For a flat wCDM model, we measure a constant dark-energy equation-of-state parameter w = -1.013(-0.073)(+0.068) (68% CL). Curvature is constrained to similar to 0.7% in the owCDM model and to similar to 2% in a model in which dark energy is allowed to vary with parameters w(0) and w(a). Further tightening the constraints on the time evolution of dark energy will require several improvements, including high-quality multi-passband photometry of a sample of several dozenz > 1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on board HST. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Union.
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4.
  • Lewis, G. R., et al. (författare)
  • The calibration of the Cassini-Huygens CAPS Electron Spectrometer
  • 2010
  • Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 58:3, s. 427-436
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the two-stage method used to calibrate the electron spectrometer (ELS), part of the plasma spectrometer (CAPS) on board the Cassini spacecraft currently in orbit around Saturn. The CAPS-ELS is a top-hat electrostatic analyser designed to measure electron fluxes between 0 5 eV and 26 keV The on-ground calibration method described here includes the production of photoelectrons, which are energised and passed into the CAPS-ELS in a purpose designed calibration facility. Knowledge of the intensity of these incident electrons and the subsequent instrument output provides an on-ground calibrated geometric factor. Comparative studies of physical quantities such as plasma density and electron differential flux calculated using on-ground calibration factor with the quantities deduced from the wave experiment and high energy electron detector provide in-flight calibration. The results of this are presented together with a comparison of the experimentally calibrated values with simulated calibration values.
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5.
  • Amanullah, Rahman, et al. (författare)
  • Spectra and Hubble Space Telescope Light Curves of Six Type Ia Supernovae at 0.511 < z < 1.12 and the Union2 Compilation
  • 2010
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 716, s. 712-738
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on work to increase the number of well-measured Type Ia supernovae (SNe Ia) at high redshifts. Light curves, including high signal-to-noise Hubble Space Telescope data, and spectra of six SNe Ia that were discovered during 2001, are presented. Additionally, for the two SNe with z > 1, we present ground-based J-band photometry from Gemini and the Very Large Telescope. These are among the most distant SNe Ia for which ground-based near-IR observations have been obtained. We add these six SNe Ia together with other data sets that have recently become available in the literature to the Union compilation. We have made a number of refinements to the Union analysis chain, the most important ones being the refitting of all light curves with the SALT2 fitter and an improved handling of systematic errors. We call this new compilation, consisting of 557 SNe, the Union2 compilation. The flat concordance ΛCDM model remains an excellent fit to the Union2 data with the best-fit constant equation-of-state parameter w = -0.997+0.050 -0.054(stat)+0.077 -0.082(stat + sys together) for a flat universe, or w = -1.038+0.056 -0.059(stat)+0.093 -0.097(stat + sys together) with curvature. We also present improved constraints on w(z). While no significant change in w with redshift is detected, there is still considerable room for evolution in w. The strength of the constraints depends strongly on redshift. In particular, at z >~ 1, the existence and nature of dark energy are only weakly constrained by the data. Based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI). STScI is operated by the Association of Universities for Research in Astronomy (AURA), Inc. under the NASA contract NAS 5-26555. The observations are associated with programs HST-GO-08585 and HST-GO-09075. Based, in part, on observations obtained at the ESO La Silla Paranal Observatory (ESO programs 67.A-0361 and 169.A-0382). Based, in part, on observations obtained at the Cerro-Tololo Inter-American Observatory (CTIO), National Optical Astronomy Observatory (NOAO). Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT). Based, in part, on observations obtained at the Gemini Observatory (Gemini programs GN-2001A-SV-19 and GN-2002A-Q-31). Based, in part on observations obtained at the Subaru Telescope. Based, in part, on data that were obtained at the W. M. Keck Observatory.
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6.
  • Dahlman, I, et al. (författare)
  • Adipose tissue pathways involved in weight loss of cancer cachexia
  • 2010
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 102:10, s. 1541-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. METHODS: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n=13) or without (n=14) cachexia. RESULTS: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia. CONCLUSIONS: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin.
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7.
  • Naldi, L., et al. (författare)
  • Comparators, study duration, outcome measures and sponsorship in therapeutic trials of psoriasis: update of the EDEN Psoriasis Survey 2001-2006
  • 2010
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 162:2, s. 384-389
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Several new therapeutic options for psoriasis have been tested in clinical trials in recent years. Choice of comparator, study duration and outcome measures are critical for interpreting application of trial results to clinical practice. Objectives We examined whether these trial aspects have changed substantially in recent years in comparison with the past. Methods A systematic search and evaluation of all randomized controlled trials (RCTs) for psoriasis published from January 2001 up to December 2006 in 14 leading medical and dermatological journals, compared with those published from 1977 to 2000. Results There were 140 RCTs of psoriasis in the period 2001-2006 and 249 in the period 1977-2000. The proportion of placebo-controlled studies increased from 44.6% to 69.3%. The median study duration increased from 7 weeks to 12 weeks. The proportion of studies adopting the Psoriasis Area and Severity Index score as an outcome increased from 30.6% to 57.7%, while the number of studies incorporating a quality of life measure increased from only one (0.4%) to 12 studies (7.7%). The proportion of studies sponsored by pharmaceutical companies increased from 61.0% to 73.7%. Conclusions Despite the increased number of new options, the number of head-to-head comparative trials has decreased and most trials focus on short-term effects, probably reflecting the increased influence of industrial sponsorship on the research agenda.
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8.
  • Astier, P., et al. (författare)
  • Extending the supernova Hubble diagram to z similar to 1.5 with the Euclid space mission
  • 2014
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 572, s. A80-
  • Tidskriftsartikel (refereegranskat)abstract
    • We forecast dark energy constraints that could be obtained from a new large sample of Type Ia supernovae where those at high redshift are acquired with the Euclid space mission. We simulate a three-prong SN survey: a z < 0.35 nearby sample (8000 SNe), a 0.2 < z < 0.95 intermediate sample (8800 SNe), and a 0.75 < z < 1.55 high-z sample (1700 SNe). The nearby and intermediate surveys are assumed to be conducted from the ground, while the high-z is a joint ground-and space-based survey. This latter survey, the Dark Energy Supernova Infra-Red Experiment (DESIRE), is designed to fit within 6 months of Euclid observing time, with a dedicated observing programme. We simulate the SN events as they would be observed in rolling-search mode by the various instruments, and derive the quality of expected cosmological constraints. We account for known systematic uncertainties, in particular calibration uncertainties including their contribution through the training of the supernova model used to fit the supernovae light curves. Using conservative assumptions and a 1D geometric Planck prior, we find that the ensemble of surveys would yield competitive constraints: a constant equation of state parameter can be constrained to sigma(omega) = 0.022, and a Dark Energy Task Force figure of merit of 203 is found for a two-parameter equation of state. Our simulations thus indicate that Euclid can bring a significant contribution to a purely geometrical cosmology constraint by extending a high-quality SN Ia Hubble diagram to z similar to 1.5. We also present other science topics enabled by the DESIRE Euclid observations.
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9.
  • Egelhofer, Thea A, et al. (författare)
  • An assessment of histone-modification antibody quality
  • 2011
  • Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 18:1, s. 91-93
  • Tidskriftsartikel (refereegranskat)abstract
    • We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/).
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11.
  • Keel, Sonja G., et al. (författare)
  • Allocation of carbon to fine root compounds and their residence times in a boreal forest depend on root size class and season
  • 2012
  • Ingår i: New Phytologist. - Malden : Wiley-Blackwell. - 0028-646X .- 1469-8137. ; 194:4, s. 972-981
  • Tidskriftsartikel (refereegranskat)abstract
    • Fine roots play a key role in the forest carbon balance, but their carbon dynamics remain largely unknown. We pulse labelled 50 m2 patches of young boreal forest by exposure to 13CO2 in early and late summer. Labelled photosynthates were traced into carbon compounds of < 1 and 13 mm diameter roots (fine roots), and into bulk tissue of these and first-order roots (root tips). Root tips were the most strongly labelled size class. Carbon allocation to all size classes was higher in late than in early summer; mean residence times (MRTs) in starch increased from 4 to 11 months. In structural compounds, MRTs were 0.8 yr in tips and 1.8 yr in fine roots. The MRT of carbon in sugars was in the range of days. Functional differences within the fine root population were indicated by carbon allocation patterns and residence times. Pronounced allocation of recent carbon and higher turnover rates in tips are associated with their role in nutrient and water acquisition. In fine roots, longer MRTs but high allocation to sugars and starch reflect their role in structural support and storage. Accounting for heterogeneity in carbon residence times will improve and most probably reduce the estimates of fine root production.
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13.
  • Krivosheeva, Olga, et al. (författare)
  • Kinetic and Equilibrium Aspects of Adsorption and Desorption of Class II Hydrophobins HFBI and HFBII at Silicon Oxynitride/Water and Air/Water Interfaces
  • 2013
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 29:8, s. 2683-2691
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydrophobins are relatively small globular proteins produced by filamentous fungi. They display unusual high surface activity and are implied as mediators of attachment to surfaces, which has resulted in high scientific and technological interest. In this work we focus on kinetic and equilibrium aspects of adsorption and desorption properties of two representatives of class II hydrophobins, namely HFBI and HFBII, at a negatively charged hydrophilic solid/water interface and at the air/water interface. The layers formed at the air/liquid interface were examined in a Langmuir trough, whereas layers formed at the solid/liquid interface were studied using dual polarization interferometry (DPI) under different flow conditions. For comparison, another globular protein, lysozyme, was also investigated. It was found that both the adsorbed amount and the adsorption kinetics were different for HFBI and HFBII, and the adsorption behavior of both hydrophobins on the negatively charged surface displayed some unusual features. For instance, even though the adsorption rate for HFBI was slowed down with increasing adsorbed amount as expected from packing constraints at the interface, the adsorption kinetics curves for HFBII displayed a region indicating adsorption cooperativity. Further, it was found that hydrophobin layers formed under flow partly desorbed when the flow was stopped, and the desorption rate for HFBII was enhanced in the presence of hydrophobins in solution.
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14.
  • Linder, H. P., et al. (författare)
  • Disentangling the influence of climatic and geological changes on species radiations
  • 2014
  • Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 41:7, s. 1313-1325
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Our aim was to seek explanations for the differences in the diversity among the austral continents by comparing the diversification rates and patterns in the grass subfamily Danthonioideae. We asked specifically whether diversification is density dependent, whether it is different for each continent, and whether immigration rates impact on diversification rates. We attempted to account for intercontinental differences by comparing the Pleistocene climatic and Neogene geomorphological histories with the inferred diversification rates. Location Mainly the Southern Hemisphere, treated as four areas for the analyses: Africa, Australia, New Zealand and South America. Methods We based our analyses on a densely sampled, dated phylogeny for the grass subfamily Danthonioideae. We compared 24 diversification models for these continental radiations, taking into account speciation models, and extinction and dispersal rates. We used available distribution data to infer the climates under which danthonioids are found, and used these to estimate the change in area and location of suitable habitats between contemporary and Last Glacial Maximum climates. We inferred the geomorphological history from the literature. Results We show that long-distance dispersal led to parallel radiations, which more than doubled the final standing diversity in the subfamily. Diversification models with the strongest support included separate time-varying diversification processes for each major geographical region. Pleistocene climatic fluctuation did not explain the intercontinental differences in diversification patterns. Main conclusions Although our results are consistent with density-dependent diversification, this explanation is not consistent with the time of arrival of danthonioids on each continent. The diversification patterns on the four major Southern Hemisphere landmasses are idiosyncratic. The two most important predictors of diversity may be the lineage-specific effect of time, and the general effect of topographical complexity and orogenesis.
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15.
  • Linder, H. Peter, et al. (författare)
  • What determines biogeographical ranges? : Historical wanderings and ecological constraints in the danthonioid grasses
  • 2013
  • Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 40:5, s. 821-834
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim We sought to understand the variables that limit the distribution range of a clade (here the danthonioid grasses). We tested time, area of origin, habitat suitability, disjunction width and nature, and wind direction as possible range determinants. Location Global, but predominantly the Southern Hemisphere. Methods We mapped the range of the subfamily Danthonioideae, and used 39,000 locality records and an ensemble modelling approach to define areas with suitable danthonioid habitat. We used a well-sampled, dated phylogeny to estimate the number and direction of historical dispersal events, based on parsimony optimization. We tested for the impact of wind direction on dispersal rate using a likelihood approach, and for the effects of barrier width with a regression approach. Results We found 17 geographically isolated areas with suitable habitats for danthonioids. All currently suitable Southern Hemisphere areas have been occupied, but three apparently suitable areas in the Northern Hemisphere have not. We infer that southern Africa was first occupied in the Oligocene and that dispersal to the other areas was initiated in the middle Miocene. Inferred dispersal rate was correlated with the width of the disjunctions, up to a distance of 5000km. There was no support for wind direction having influenced differences in dispersal rate. Main conclusions The current range of the Danthonioideae can be predicted ecologically (areas with suitable habitat) and historically (the width of the disjunctions separating the areas with suitable habitat and the area of origin). The direction of dispersal is dictated by the area of origin and by serendipity: there is no evidence for general patterns of dispersal, for example for dispersal occurring more frequently over land than over sea or in an easterly versus a westerly direction around the Southern Hemisphere. Thus the range and range-filling of Danthonioideae can be accounted for by surprisingly few variables: habitat suitability, distance between suitable areas, and area of origin.
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17.
  • Nording, Malin Linder, et al. (författare)
  • Individual Variation in Lipidomic Profiles of Healthy Subjects in Response to Omega-3 Fatty Acids
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:10, s. e76575-
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of omega 3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined omega 3 intervention. Methods: The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of omega 3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA]). Results: Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r(2)=0.93). However, strikingly divergent responses among individuals were also observed. Both omega 3 and omega 6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E-2 (PGE(2)) and thromboxane B2 (TXB2), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase. Conclusions: Our results show that certain defined responses to omega 3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to omega 3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of omega 3 interventions in modifying disease risk and determining metabolic phenotype.
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18.
  • Riddle, Nicole C, et al. (författare)
  • Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin
  • 2011
  • Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 21:2, s. 147-163
  • Tidskriftsartikel (refereegranskat)abstract
    • Eukaryotic genomes are packaged in two basic forms, euchromatin and heterochromatin. We have examined the composition and organization of Drosophila melanogaster heterochromatin in different cell types using ChIP-array analysis of histone modifications and chromosomal proteins. As anticipated, the pericentric heterochromatin and chromosome 4 are on average enriched for the "silencing" marks H3K9me2, H3K9me3, HP1a, and SU(VAR)3-9, and are generally depleted for marks associated with active transcription. The locations of the euchromatin-heterochromatin borders identified by these marks are similar in animal tissues and most cell lines, although the amount of heterochromatin is variable in some cell lines. Combinatorial analysis of chromatin patterns reveals distinct profiles for euchromatin, pericentric heterochromatin, and the 4th chromosome. Both silent and active protein-coding genes in heterochromatin display complex patterns of chromosomal proteins and histone modifications; a majority of the active genes exhibit both "activation" marks (e.g., H3K4me3 and H3K36me3) and "silencing" marks (e.g., H3K9me2 and HP1a). The hallmark of active genes in heterochromatic domains appears to be a loss of H3K9 methylation at the transcription start site. We also observe complex epigenomic profiles of intergenic regions, repeated transposable element (TE) sequences, and genes in the heterochromatic extensions. An unexpectedly large fraction of sequences in the euchromatic chromosome arms exhibits a heterochromatic chromatin signature, which differs in size, position, and impact on gene expression among cell types. We conclude that patterns of heterochromatin/euchromatin packaging show greater complexity and plasticity than anticipated. This comprehensive analysis provides a foundation for future studies of gene activity and chromosomal functions that are influenced by or dependent upon heterochromatin.
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