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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. |
- de Vries, Paul S., et al.
(författare)
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Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5x10(-8) is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5x10(-8)), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
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| 4. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 5. |
- Desjardins, Kewin, et al.
(författare)
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Characterization of a back-illuminated CMOS camera for soft x-ray coherent scattering
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A commercial scientific camera has been adapted and characterized at the SOLEIL Synchrotron with the aim to improve the acquisition capabilities on the soft X-ray coherent scattering experimental station at SEXTANTS beamline. This device is equipped by the last generation of back side illuminated scientific CMOS (BSI-sCMOS) of 2048 by 2048 pixels of 11 μm2 able to acquire low noise images with a frame rate up to 48 Hz. The camera's performance measurements have been done and shows a good level of readout noise, a large full-well capacity, a medium dark current and a good homogeneity, respectively, 1.6 e- rms (in High Gain mode), 80 000 e- (in Low Gain mode),<5 e-/pixel/s and ∼ 1%. The quantum efficiency (QE) measurement has been performed at the soft x-ray branch of the METROLOGIE beamline and gives a relatively good agreement with the expected theoretical values. Finally, the demonstration of the camera's efficiency and of the gain in useful time measurement related to the high frame rate have been performed with a series of Airy patterns images compared with an image recorded using the standard BSI-CDD already in operation at the SEXTANTS beamline.
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| 6. |
- Griesmayer, E., et al.
(författare)
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Applications of single-crystal CVD diamond XBPM detectors with nanometre x-ray beams
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Measurements with a Diamond XBPM were carried out at the MAX IV Laboratory, Lund, Sweden, at the NanoMAX beam line. This was the first investigation of a Diamond XBPM detector with nanometre beams. The effect of diffusion, as well as the position resolution at the smallest available beam sizes were studied.
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| 7. |
- Marcouille, O., et al.
(författare)
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Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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| 8. |
- Plivelic, Tomás S., et al.
(författare)
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X-ray tracing, design and construction of an optimized optics scheme for CoSAXS, the small angle x-ray scattering beamline at MAX IV laboratory
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A novel optical design for a flexible SAXS beamline at a modern synchrotron has been implemented for the CoSAXS beamline at the 3GeV ring at the MAX TV Laboratory. The performance of the beamline has been simulated through combined ray tracing and wave propagation with the code xrt taking into account the low emittance and highly coherent beam of MAX TV and the short inter-optics distances of the beamline. The total photon flux is estimated to be 1012-1013 ph/s with the coherent flux portion up to 10 % at 7.1 keV. The inhomogeneities in the X-ray beam arising from use of real (non-idealised) mirror surfaces are also modelled using the measured slope profiles of the mirrors. Strategies to mitigate these inhomogeneities are discussed. The optical components for CoSAXS have been constructed and beamline commissioning will start in 2019.
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