| 1. |
- 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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| 2. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 3. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 4. |
- Vandenbussche, B., et al.
(författare)
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The beta Pictoris disk imaged by Herschel PACS and SPIRE
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L133
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Tidskriftsartikel (refereegranskat)abstract
- We obtained Herschel PACS and SPIRE images of the thermal emission of the debris disk around the A5V star beta Pic. The disk is well resolved in the PACS filters at 70, 100, and 160 mu m. The surface brightness profiles between 70 and 160 mu m show no significant asymmetries along the disk, and are compatible with 90% of the emission between 70 and 160 mu m originating in a region closer than 200 AU to the star. Although only marginally resolving the debris disk, the maps obtained in the SPIRE 250-500 mu m filters provide full-disk photometry, completing the SED over a few octaves in wavelength that had been previously inaccessible. The small far-infrared spectral index (beta = 0.34) indicates that the grain size distribution in the inner disk (
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| 5. |
- Acke, B., et al.
(författare)
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Herschel images of Fomalhaut An extrasolar Kuiper belt at the height of its dynamical activity
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 540, s. Article Number: A125 -
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Tidskriftsartikel (refereegranskat)abstract
- Context. Fomalhaut is a young (2 +/- 1 x 10(8) years), nearby (7.7 pc), 2 M-circle dot star that is suspected to harbor an infant planetary system, interspersed with one or more belts of dusty debris. Aims. We present far-infrared images obtained with the Herschel Space Observatory with an angular resolution between 5.7 '' and 36.7 '' at wavelengths between 70 mu m and 500 mu m. The images show the main debris belt in great detail. Even at high spatial resolution, the belt appears smooth. The region in between the belt and the central star is not devoid of material; thermal emission is observed here as well. Also at the location of the star, excess emission is detected. We aim to construct a consistent image of the Fomalhaut system. Methods. We use a dynamical model together with radiative-transfer tools to derive the parameters of the debris disk. We include detailed models of the interaction of the dust grains with radiation, for both the radiation pressure and the temperature determination. Comparing these models to the spatially resolved temperature information contained in the images allows us to place strong constraints on the presence of grains that will be blown out of the system by radiation pressure. We use this to derive the dynamical parameters of the system. Results. The appearance of the belt points toward a remarkably active system in which dust grains are produced at a very high rate by a collisional cascade in a narrow region filled with dynamically excited planetesimals. Dust particles with sizes below the blow-out size are abundantly present. The equivalent of 2000 one-km-sized comets are destroyed every day, out of a cometary reservoir amounting to 110 Earth masses. From comparison of their scattering and thermal properties, we find evidence that the dust grains are fluffy aggregates, which indicates a cometary origin. The excess emission at the location of the star may be produced by hot dust with a range of temperatures, but may also be due to gaseous free-free emission from a stellar wind.
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| 6. |
- Greaves, J. S., et al.
(författare)
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EXTREME CONDITIONS IN A CLOSE ANALOG TO THE YOUNG SOLAR SYSTEM : HERSCHEL OBSERVATIONS OF is an element of ERIDANI
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 791:1, s. L11-
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Tidskriftsartikel (refereegranskat)abstract
- Far-infrared Herschel images of the is an element of Eridani system, seen at a fifth of the Sun's present age, resolve two belts of debris emission. Fits to the 160 mu m PACS image yield radial spans for these belts of 12-16 and 54-68 AU. The south end of the outer belt is approximate to 10% brighter than the north end in the PACS+SPIRE images at 160, 250, and 350 mu m, indicating a pericenter glow attributable to a planet c From this asymmetry and an upper bound on the offset of the belt center, this second planet should be mildly eccentric (e(c) approximate to 0.03-0.3). Compared to the asteroid and Kuiper Belts of the young Sun, the is an element of Eri belts are intermediate in brightness and more similar to each other, with up to 20 km sized collisional fragments in the inner belt totaling approximate to 5% of an Earth mass. This reservoir may feed the hot dust close to the star and could send many impactors through the Habitable Zone, especially if it is being perturbed by the suspected planet is an element of Eri b, at semi-major axis approximate to 3 AU.
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| 7. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 8. |
- Scuteri, Angelo, et al.
(författare)
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Arterial stiffness and influences of the metabolic syndrome: A cross-countries study.
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 233:2, s. 654-660
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Tidskriftsartikel (refereegranskat)abstract
- Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in ≥3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components - even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus - in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV).
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| 9. |
- Sibthorpe, B., et al.
(författare)
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The Vega debris disc: A view from Herschel
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L130
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Tidskriftsartikel (refereegranskat)abstract
- We present five band imaging of the Vega debris disc obtained using the Herschel Space Observatory. These data span a wavelength range of 70-500 mu m with full-width half-maximum angular resolutions of 5.6-36.9 ''. The disc is well resolved in all bands, with the ring structure visible at 70 and 160 mu m. Radial profiles of the disc surface brightness are produced, and a disc radius of 11 '' (similar to 85AU) is determined. The disc is seen to have a smooth structure thoughout the entire wavelength range, suggesting that the disc is in a steady state, rather than being an ephemeral structure caused by the recent collision of two large planetesimals.
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| 10. |
- Greaves, J. S., et al.
(författare)
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Extreme Conditions in a Close Analog to the Young Solar System: Herschel Observations of ∈ Eridani
- 2014
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 791:1
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Tidskriftsartikel (refereegranskat)abstract
- Far-infrared Herschel images of the is an element of Eridani system, seen at a fifth of the Sun's present age, resolve two belts of debris emission. Fits to the 160 mu m PACS image yield radial spans for these belts of 12-16 and 54-68 AU. The south end of the outer belt is approximate to 10% brighter than the north end in the PACS+SPIRE images at 160, 250, and 350 mu m, indicating a pericenter glow attributable to a planet "c" From this asymmetry and an upper bound on the offset of the belt center, this second planet should be mildly eccentric (e(c) approximate to 0.03-0.3). Compared to the asteroid and Kuiper Belts of the young Sun, the is an element of Eri belts are intermediate in brightness and more similar to each other, with up to 20 km sized collisional fragments in the inner belt totaling approximate to 5% of an Earth mass. This reservoir may feed the hot dust close to the star and could send many impactors through the Habitable Zone, especially if it is being perturbed by the suspected planet is an element of Eri b, at semi-major axis approximate to 3 AU.
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