| 1. |
- Bravo, L, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Tabiri, S, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- van Haarlem, M. P., et al.
(författare)
-
LOFAR : The LOw-Frequency ARray
- 2013
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53
-
Tidskriftsartikel (refereegranskat)abstract
- LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
|
|
| 8. |
- van Cappellen, W., et al.
(författare)
-
Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
-
Tidskriftsartikel (refereegranskat)abstract
- We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
|
|
| 9. |
- Griffin, M. J., et al.
(författare)
-
The Herschel-SPIRE instrument and its in-flight performance
- 2010
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
-
Tidskriftsartikel (refereegranskat)abstract
- The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
|
|
| 10. |
- Zucca, P., et al.
(författare)
-
Shock location and CME 3D reconstruction of a solar type II radio burst with LOFAR
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Type II radio bursts are evidence of shocks in the solar atmosphere and inner heliosphere that emit radio waves ranging from sub-meter to kilometer lengths. These shocks may be associated with coronal mass ejections (CMEs) and reach speeds higher than the local magnetosonic speed. Radio imaging of decameter wavelengths (20-90 MHz) is now possible with the Low Frequency Array (LOFAR), opening a new radio window in which to study coronal shocks that leave the inner solar corona and enter the interplanetary medium and to understand their association with CMEs. Aims. To this end, we study a coronal shock associated with a CME and type II radio burst to determine the locations at which the radio emission is generated, and we investigate the origin of the band-splitting phenomenon. Methods. The type II shock source-positions and spectra were obtained using 91 simultaneous tied-array beams of LOFAR, and the CME was observed by the Large Angle and Spectrometric Coronagraph (LASCO) on board the Solar and Heliospheric Observatory (SOHO) and by the COR2A coronagraph of the SECCHI instruments on board the Solar Terrestrial Relation Observatory (STEREO). The 3D structure was inferred using triangulation of the coronographic observations. Coronal magnetic fields were obtained from a 3D magnetohydrodynamics (MHD) polytropic model using the photospheric fields measured by the Heliospheric Imager (HMI) on board the Solar Dynamic Observatory (SDO) as lower boundary. Results. The type II radio source of the coronal shock observed between 50 and 70 MHz was found to be located at the expanding flank of the CME, where the shock geometry is quasi-perpendicular with theta(Bn)similar to 70 degrees. The type II radio burst showed first and second harmonic emission; the second harmonic source was cospatial with the first harmonic source to within the observational uncertainty. This suggests that radio wave propagation does not alter the apparent location of the harmonic source. The sources of the two split bands were also found to be cospatial within the observational uncertainty, in agreement with the interpretation that split bands are simultaneous radio emission from upstream and downstream of the shock front. The fast magnetosonic Mach number derived from this interpretation was found to lie in the range 1.3-1.5. The fast magnetosonic Mach numbers derived from modelling the CME and the coronal magnetic field around the type II source were found to lie in the range 1.4-1.6.
|
|
| 11. |
- Oostrum, L. C., et al.
(författare)
-
Repeating fast radio bursts with WSRT/Apertif
- 2020
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Repeating fast radio bursts (FRBs) present excellent opportunities to identify FRB progenitors and host environments as well as to decipher the underlying emission mechanism. Detailed studies of repeating FRBs might also hold clues as to the origin of FRBs as a population. Aims. We aim to detect bursts from the first two repeating FRBs, FRB 121102 (R1) and FRB 180814.J0422+73 (R2), and to characterise their repeat statistics. We also want to significantly improve the sky localisation of R2 and identify its host galaxy. Methods. We used the Westerbork Synthesis Radio Telescope to conduct extensive follow-up of these two repeating FRBs. The new phased-array feed system, Apertif, allows one to cover the entire sky position uncertainty of R2 with fine spatial resolution in a single pointing. The data were searched for bursts around the known dispersion measures of the two sources. We characterise the energy distribution and the clustering of detected R1 bursts. Results. We detected 30 bursts from R1. The non-Poissonian nature is clearly evident from the burst arrival times, which is consistent with earlier claims. Our measurements indicate a dispersion measure (DM) of 563.5(2) pc cm(-3), suggesting a significant increase in DM over the past few years. Assuming a constant position angle across the burst, we place an upper limit of 8% on the linear polarisation fraction for the brightest burst in our sample. We did not detect any bursts from R2. Conclusions. A single power-law might not fit the R1 burst energy distribution across the full energy range or widely separated detections. Our observations provide improved constraints on the clustering of R1 bursts. Our stringent upper limits on the linear polarisation fraction imply a significant depolarisation, either intrinsic to the emission mechanism or caused by the intervening medium at 1400 MHz, which is not observed at higher frequencies. The non-detection of any bursts from R2, despite nearly 300 h of observations, implies either a highly clustered nature of the bursts, a steep spectral index, or a combination of the two assuming that the source is still active. Another possibility is that R2 has turned off completely, either permanently or for an extended period of time.
|
|
| 12. |
- Adams, E. A. K., et al.
(författare)
-
First release of Apertif imaging survey data
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Apertif is a phased-array feed system for the Westerbork Synthesis Radio Telescope, providing forty instantaneous beams over 300 MHz of bandwidth. A dedicated survey program utilizing this upgrade started on 1 July 2019, with the last observations taken on 28 February 2022. The imaging survey component provides radio continuum, polarization, and spectral line data. Aims. Public release of data is critical for maximizing the legacy of a survey. Toward that end, we describe the release of data products from the first year of survey operations, through 30 June 2020. In particular, we focus on defining quality control metrics for the processed data products. Methods. The Apertif imaging pipeline, Apercal, automatically produces non-primary beam corrected continuum images, polarization images and cubes, and uncleaned spectral line and dirty beam cubes for each beam of an Apertif imaging observation. For this release, processed data products are considered on a beam-by-beam basis within an observation. We validate the continuum images by using metrics that identify deviations from Gaussian noise in the residual images. If the continuum image passes validation, we release all processed data products for a given beam. We apply further validation to the polarization and line data products and provide flags indicating the quality of those data products. Results. We release all raw observational data from the first year of survey observations, for a total of 221 observations of 160 independent target fields, covering approximately one thousand square degrees of sky. Images and cubes are released on a per beam basis, and 3374 beams (of 7640 considered) are released. The median noise in the continuum images is 41.4 uJy beam(-1), with a slightly lower median noise of 36.9 uJy beam(-1) in the Stokes V polarization image. The median angular resolution is 11.6 ''/sin delta. The median noise for all line cubes, with a spectral resolution of 36.6 kHz, is 1.6 mJy beam(-1), corresponding to a 3-sigma H i column density sensitivity of 1.8 x 10(20) atoms cm(-2) over 20 km s(-1) (for a median angular resolution of 24 '' x 15 ''). Line cubes at lower frequency have slightly higher noise values, consistent with the global RFI environment and overall Apertif system performance. We also provide primary beam images for each individual Apertif compound beam. The data are made accessible using a Virtual Observatory interface and can be queried using a variety of standard tools.
|
|
| 13. |
- Imanishi, T., et al.
(författare)
-
Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
-
Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
-
Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
|
|
| 14. |
- van Dongen, J, et al.
(författare)
-
DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
- 2021
-
Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:6, s. 2148-2162
-
Tidskriftsartikel (refereegranskat)abstract
- DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
|
|
| 15. |
- Arias, M., et al.
(författare)
-
Low-frequency radio absorption in Cassiopeia A
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Cassiopeia A is one of the best-studied supernova remnants. Its bright radio and X-ray emission is due to shocked ejecta. Cas A is rather unique in that the unshocked ejecta can also be studied: through emission in the infrared, the radio-active decay of Ti-44, and the low-frequency free-free absorption caused by cold ionised gas, which is the topic of this paper. Aims. Free-free absorption processes are affected by the mass, geometry, temperature, and ionisation conditions in the absorbing gas. Observations at the lowest radio frequencies can constrain a combination of these properties. Methods. We used Low Frequency Array (LOFAR) Low Band Antenna observations at 30-77 MHz and Very Large Array (VLA) L-band observations at 1-2 GHz to fit for internal absorption as parametrised by the emission measure. We simultaneously fit multiple UV-matched images with a common resolution of 17 '' (this corresponds to 0.25 pc for a source at the distance of Cas A). The ample frequency coverage allows us separate the relative contributions from the absorbing gas, the unabsorbed front of the shell, and the absorbed back of the shell to the emission spectrum. We explored the effects that a temperature lower than the similar to 100-500 K proposed from infrared observations and a high degree of clumping can have on the derived physical properties of the unshocked material, such as its mass and density. We also compiled integrated radio flux density measurements, fit for the absorption processes that occur in the radio band, and considered their effect on the secular decline of the source. Results. We find a mass in the unshocked ejecta of M = 2.95 +/- 0.48 M-circle dot for an assumed gas temperature of T = 100 K. This estimate is reduced for colder gas temperatures and, most significantly, if the ejecta are clumped. We measure the reverse shock to have a radius of 114 '' +/- 6 '' and be centred at 23:23:26, +58:48:54 (J2000). We also find that a decrease in the amount of mass in the unshocked ejecta (as more and more material meets the reverse shock and heats up) cannot account for the observed low-frequency behaviour of the secular decline rate. Conclusions. To reconcile our low-frequency absorption measurements with models that reproduce much of the observed behaviour in Cas A and predict little mass in the unshocked ejecta, the ejecta need to be very clumped or the temperature in the cold gas needs to be low (similar to 10 K). Both of these options are plausible and can together contribute to the high absorption value that we find.
|
|
| 16. |
- Broderick, J. W., et al.
(författare)
-
LOFAR 144-MHz follow-up observations of GW170817
- 2020
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 494:4, s. 5110-5117
-
Tidskriftsartikel (refereegranskat)abstract
- We present low-radio-frequency follow-up observations of AT 2017gfo, the electromagnetic counterpart of GW170817, which was the first binary neutron star merger to be detected by Advanced LIGO-Virgo. These data, with a central frequency of 144 MHz, were obtained with LOFAR, the Low-Frequency Array. The maximum elevation of the target is just 13 degrees.7 when observed with LOFAR, making our observations particularly challenging to calibrate and significantly limiting the achievable sensitivity. On time-scales of 130-138 and 371-374 d after the merger event, we obtain 3s upper limits for the afterglow component of 6.6 and 19.5mJy beam(-1), respectively. Using our best upper limit and previously published, contemporaneous higher frequency radio data, we place a limit on any potential steepening of the radio spectrum between 610 and 144 MHz: the two-point spectral index alpha(610)(144) greater than or similar to -2.5. We also show that LOFAR can detect the afterglows of future binary neutron star merger events occurring at more favourable elevations.
|
|
| 17. |
- Carninci, P, et al.
(författare)
-
The transcriptional landscape of the mammalian genome
- 2005
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
|
|
| 18. |
- de Leede, E. M., et al.
(författare)
-
Common variables in European pancreatic cancer registries: The introduction of the EURECCA pancreatic cancer project
- 2016
-
Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 42:9, s. 1414-1419
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCAs newest project is collecting data on pancreatic cancer in several European countries. Methods: National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. Results: Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. Conclusions: A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.
|
|
| 19. |
- Mulder, Renée L., et al.
(författare)
-
Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer : recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
- 2021
-
Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:2, s. 68-80
-
Forskningsöversikt (refereegranskat)abstract
- Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.
|
|
| 20. |
- Saliba-Gustafsson, P., et al.
(författare)
-
Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
-
Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Bogie, JFJ, et al.
(författare)
-
Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain
- 2020
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:5
-
Tidskriftsartikel (refereegranskat)abstract
- Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
|
|
| 25. |
- Bonomi, A, et al.
(författare)
-
Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
-
Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
-
Tidskriftsartikel (refereegranskat)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
|
|
