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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 4. |
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| 5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Abramowski, A., et al.
(författare)
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The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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Tidskriftsartikel (refereegranskat)abstract
- The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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| 7. |
- Acciari, V. A., et al.
(författare)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Tidskriftsartikel (refereegranskat)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 8. |
- Acero, F., et al.
(författare)
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Detection of Gamma Rays from a Starburst Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5956, s. 1080-1082
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Tidskriftsartikel (refereegranskat)abstract
- Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of similar to 10(15) electron volts. We report the detection of gamma rays-tracers of such cosmic rays-from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H. E. S. S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.
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| 9. |
- Acero, F., et al.
(författare)
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Discovery and follow-up studies of the extended, off-plane, VHE gamma-ray source HESS J1507-622
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 525, s. A45-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The detection of gamma-rays in the very-high-energy (VHE) range (100 GeV-100 TeV) offers the possibility of studying the parent population of ultrarelativistic particles found in astrophysical sources, so it is useful for understanding the underlying astrophysical processes in nonthermal sources. Aims. The discovery of the VHE gamma-ray source HESS J1507-622 is reported and possibilities regarding its nature are investigated. Methods. The H. E. S. S. array of imaging atmospheric Cherenkov telescopes (IACTs) has a high sensitivity compared with previous instruments (similar to 1% of the Crab flux in 25 h observation time for a 5 sigma point-source detection) and has a large field of view (similar to 5 degrees in diameter). HESS J1507-622 was discovered within the ongoing H. E. S. S. survey of the inner Galaxy, and the source was also studied by means of dedicated multiwavelength observations. Results. A Galactic gamma-ray source, HESS J1507-622, located similar to 3.5 degrees. from the Galactic plane was detected with a statistical significance >9 sigma. Its energy spectrum is well fitted by a power law with spectral index Gamma = 2.24 +/- 0.16(stat) +/- 0.20(sys) and a flux above 1 TeV of (1.5 +/- 0.4(stat) +/- 0.3(sys)) x 10(-12) cm(-2) s(-1). Possible interpretations (considering both hadronic and leptonic models) of the VHE gamma-ray emission are discussed in the absence of an obvious counterpart.
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| 10. |
- Acero, F., et al.
(författare)
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Localizing the VHE gamma-ray source at the Galactic Centre
- 2010
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:3, s. 1877-1882
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Tidskriftsartikel (refereegranskat)abstract
- The inner 10 pc of our Galaxy contains many counterpart candidates of the very high energy (VHE; > 100 GeV) gamma-ray point source HESS J1745-290. Within the point spread function of the H.E.S.S. measurement, at least three objects are capable of accelerating particles to VHE and beyond and of providing the observed gamma-ray flux. Previous attempts to address this source confusion were hampered by the fact that the projected distances between these objects were of the order of the error circle radius of the emission centroid (34 arcsec, dominated by the pointing uncertainty of the H.E.S.S. instrument). Here we present H.E.S.S. data of the Galactic Centre region, recorded with an improved control of the instrument pointing compared to H.E.S.S. standard pointing procedures. Stars observed during gamma-ray observations by optical guiding cameras mounted on each H.E.S.S. telescope are used for off-line pointing calibration, thereby decreasing the systematic pointing uncertainties from 20 to 6 arcsec per axis. The position of HESS J1745-290 is obtained by fitting a multi-Gaussian profile to the background-subtracted gamma-ray count map. A spatial comparison of the best-fitting position of HESS J1745-290 with the position and morphology of candidate counterparts is performed. The position is, within a total error circle radius of 13 arcsec, coincident with the position of the supermassive black hole Sgr A* and the recently discovered pulsar wind nebula candidate G359.95-0.04. It is significantly displaced from the centroid of the supernova remnant Sgr A East, excluding this object with high probability as the dominant source of the VHE gamma-ray emission.
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