| 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. |
- Amemiya, Chris T., et al.
(författare)
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The African coelacanth genome provides insights into tetrapod evolution
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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| 3. |
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| 5. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
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| 8. |
- Braasch, Ingo, et al.
(författare)
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The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 427-437
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Tidskriftsartikel (refereegranskat)abstract
- To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
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| 9. |
- Brownbill, Paul, et al.
(författare)
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An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy
- 2016
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238. ; 64, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice.
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| 15. |
- Gebhardt, T., et al.
(författare)
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Ab initio lattice stability of fcc and hcp Fe-Mn random alloys
- 2010
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 22:29, s. 295402-
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the lattice stability of face centred cubic (fcc) versus hexagonal close packed (hcp) Fe-Mn random alloys using ab initio calculations. In the calculations we considered the antiferromagnetic order of local moments, which for fcc alloys models the magnetic configuration of this phase at room temperature (below its Neel temperature) as well as their complete disorder, corresponding to paramagnetic fcc and hcp alloys. For both cases, the results are consistent with our thermodynamic calculations, obtained within the Calphad approach. For the room temperature magnetic configuration, the cross-over of the total energies of the hcp phase and the fcc phase of Fe-Mn alloys is at the expected Mn content, whereas for the magnetic configuration above the fcc Neel temperature, the hcp lattice is more stable within the whole composition range studied. The increase of the total energy difference between hcp and antiferromagnetic fcc due to additions of Mn as well as the stabilizing effect of antiferromagnetic ordering on the fcc phase are well displayed. These results are of relevance for understanding the deformation mechanisms of these random alloys.
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| 16. |
- Gebhardt, Thomas, et al.
(författare)
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Elastic properties of fcc Fe-Mn-X (X = Al, Si) alloys studied by theory and experiment
- 2011
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 59:8, s. 3145-3155
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the influence of Al and Si additions on the elastic properties of face-centered cubic (fcc) Fe-Mn random alloys with Fe/Mn ratios of 4.00 and 2.33 using ab initio calculations. When Al is added up to 8 at.% the shearing elastic constants (C-11-C-12)/2 and C-44 decrease, resulting in a drop of similar to 20% in shear and similar to 19% in Young's modulus. In fcc Fe-Mn-Si alloys, the trends in the elastic constants are similar, but less drastic, with a similar to 7% shear and similar to 6% Young's modulus decrease when Si is added up to 8 at.%. The Fe/Mn ratio exhibits a minor influence on the shear and Young's modulus values at constant Al and Si contents. To assess the quality of the ab initio data Fe-Mn-Al and Fe-Mn-Si thin films with an fcc structure were combinatorially synthesized and the elastic properties measured using nanoindentation. For both systems the measured and calculated lattice parameters are in good agreement. Although the measured Young's modulus data showed significant scatter due to the high surface roughness, they are in good agreement with the predicted values. For the Fe-Mn-Al system the calculations generally underestimate the experimental data by similar to 15%. For the Fe-Mn-Si system the calculated data are in general lower by similar to 10% than the experimentally determined values. The presented results are of relevance for multicomponent alloy design, since the effect of Si and Al addition on the elastic properties of Fe-Mn alloys can be predicted based on ab initio data.
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| 17. |
- Gebhardt, T, et al.
(författare)
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Influence of chemical composition and magnetic effects on the elastic properties of fcc Fe-Mn alloys
- 2011
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Ingår i: Acta Materialia. - : Elsevier Science B.V., Amsterdam.. - 1359-6454 .- 1873-2453. ; 59:4, s. 1493-1501
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the Mn content on the elastic properties of face centered cubic Fe-Mn alloys was studied using the combinatorial approach. Fe-Mn thin films with a graded chemical composition were synthesized. Nanoindentation experiments were carried out to investigate the elastic properties as a function of the Mn content. As the Mn content increases from similar to 23 to similar to 39 at.%, the average bulk modulus varies from 143 to 105 GPa. Ab initio calculations served to probe the impact of magnetic effects on the elastic properties. The magnetic state description with disordered local moments yields the best agreement with the experimental results, whereas with non-magnetic and antiferromagnetic configurations the bulk modulus is overestimated. The strong impact of the magnetic configuration may be understood based on the differences in the chemical bonding and the magnetovolume effect. It is suggested that, owing to minute energy differences of competing antiferromagnetic configurations, a mixture of these with a "notional magnetic disorder" is present, which is in fact well described by the disordered local moments model. These results show that the combinatorial thin film synthesis with subsequent nanoindentation is an appropriate tool for investigating the elastic properties of Fe-Mn alloys systematically as a function of the chemical composition, to validate theoretical models.
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| 18. |
- Gebhardt, T., et al.
(författare)
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The influence of additions of Al and Si on the lattice stability of fcc and hcp Fe-Mn random alloys
- 2011
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 23:24, s. 246003-
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the influence of additions of Al and Si on the lattice stability of face-centred-cubic (fcc) versus hexagonal-closed-packed (hcp) Fe-Mn random alloys, considering the influence of magnetism below and above the fcc Neel temperature. Employing two different ab initio approaches with respect to basis sets and treatment of magnetic and chemical disorder, we are able to quantify the predictive power of the ab initio methods. We find that the addition of Al strongly stabilizes the fcc lattice independent of the regarded magnetic states. For Si a much stronger dependence on magnetism is observed. Compared to Al, almost no volume change is observed as Si is added to Fe-Mn, indicating that the electronic contributions are responsible for stabilization/destabilization of the fcc phase.
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| 19. |
- Girardo, Jean-Baptiste, et al.
(författare)
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Stabilization of sawteeth with third harmonic deuterium ICRF-accelerated beam in JET plasmas
- 2016
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Ingår i: Physics of Plasmas. - : AMER INST PHYSICS. - 1070-664X .- 1089-7674. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Sawtooth stabilisation by fast ions is investigated in deuterium (D) and D-helium 3 (He3) plasmas of JET heated by deuterium Neutral Beam Injection combined in synergy with Ion Cyclotron Resonance Heating (ICRH) applied on-axis at 3rd beam cyclotron harmonic. A very significant increase in the sawtooth period is observed, caused by the ICRH-acceleration of the beam ions born at 100 keV to the MeV energy range. Four representative sawteeth from four different discharges are compared with Porcelli's model. In two discharges, the sawtooth crash appears to be triggered by core-localized Toroidal Alfven Eigenmodes inside the q = 1 surface (also called "tornado" modes) which expel the fast ions from within the q = 1 surface, over time scales comparable with the sawtooth period. Two other discharges did not exhibit fast ion-driven instabilities in the plasma core, and no degradation of fast ion confinement was found in both modelling and direct measurements of fast ion profile with the neutron camera. The developed sawtooth scenario without fast ion-driven instabilities in the plasma core is of high interest for the burning plasmas. Possible causes of the sawtooth crashes on JET are discussed.
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| 20. |
- Güsten, R., et al.
(författare)
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APEX - The Atacama Pathfinder Experiment
- 2006
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 6267 I
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Konferensbidrag (refereegranskat)abstract
- APEX, the Atacama Pathfinder Experiment, has been successfully commissioned and is in operation now. This novel submillimeter telescope is located at 5107 m altitude on Llano de Chajnantor in the Chilean High Andes, on what is considered one of the world's outstanding sites for submillimeter astronomy. The primary reflector with 12 m diameter has been carefully adjusted by means of holography. Its surface smoothness of 17-18 μm makes APEX suitable for observations up to 200 μm, through all atmospheric submm windows accessible from the ground.
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| 21. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 22. |
- Karlsson, Johan, et al.
(författare)
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Laplace model for multi-axial responses in fatigue analysis of a cultivator frame
- 2014
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Ingår i: Proceedings of the 3rd International Commercial Vehicle Technology Symposium (CVT 2014). ; , s. 141-150, s. 141-150
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Konferensbidrag (refereegranskat)abstract
- This paper reviews means for fatigue damage rates estimation using Laplace distributed multiaxial loads. The model is suitable for description of stresses containing transients of random amplitudes and locations. Explicit formulas for computing the expected value of rainflow damage index as a function of excess kurtosis are given for correlated loads. A Laplace model is used to describe variability of forces and bending moments measured at some location on a cultivator frame. An example of actual cultivator data is used to illustrate the model and demonstrate the accuracy of damage index prediction.
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| 23. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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