| 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. |
- Bordogna, Marco Tito, et al.
(författare)
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MUSCAT experiment : active free falling units for in situ measurements of temperature and density in the middle atmosphere
- 2013
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Ingår i: European Space Agency. - ESTEC, Noordwijk, The Netherlands : ESA Communications. - 9789290922858 ; , s. 575-582
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The main scientific objective of the MUSCAT Experimentis to develop a technique to reconstruct temperatures and density profiles in the middle atmosphere using active spherical probes. The MUSCAT experiment was launched on May 9, 2013 on the REXUS-13 sounding rocket from Esrange, in northern Sweden. The experiment ejected four probes that collected raw GPS signal. The experiment design and preliminary results are presented here.
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| 3. |
- Aldrin-Kirk, Patrick, et al.
(författare)
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Novel AAV-Based Rat Model of Forebrain Synucleinopathy Shows Extensive Pathologies and Progressive Loss of Cholinergic Interneurons.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB) are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV) vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable to α-synuclein over-expression. This animal model provides a powerful new tool for studies of neuronal degeneration in conditions of widespread cortical α-synuclein pathology, such as DLB, as well an attractive model for the exploration of novel biomarkers.
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| 4. |
- Assimes, Themistocles L., et al.
(författare)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 5. |
- Barkowsky, Marcus, et al.
(författare)
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Subjective and objective visual quality assessment in the context of stereoscopic 3D-TV
- 2013
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Ingår i: 3D-TV System with Depth-Image-Based Rendering: Architectures, Techniques and Challenges. - New York, NY : Springer New York. - 9781441999641 - 1441999639 - 9781441999634 ; , s. 413-437
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Subjective and objective visual quality assessment in the context of stereoscopic three-dimensional TV (3D-TV) is still in the nascent stage and needs to consider the effect of the added depth dimension. As a matter of fact, quality assessment of 3D-TV cannot be considered as a trivial extension of two-dimensional (2D) cases. Furthermore, it may also introduce negative effects not experienced in 2D, e.g., discomfort or nausea. Based on efforts initiated within the cost action ICT 1003 QUALINET, this chapter discusses current challenges in relation to subjective and objective visual quality assessment for stereo-based 3D-TV. Two case studies are presented to illustrate the current state of the art and some of the remaining challenges.
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| 6. |
- Barkowsky, Marcus, et al.
(författare)
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Towards standardized 3DTV QoE assessment : Cross-lab study on display technology and viewing environment parameters
- 2013
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819494214
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Konferensbidrag (refereegranskat)abstract
- Subjective assessment of Quality of Experience in stereoscopic 3D requires new guidelines for the environmental setup as existing standards such as ITU-R BT.500 may no longer be appropriate. A first step is to perform cross-lab experiments in different viewing conditions on the same video sequences. Three international labs performed Absolute Category Rating studies on a freely available video database containing degradations that are mainly related to video quality degradations. Different conditions have been used in the labs: Passive polarized displays, active shutter displays, differences in viewing distance, the number of parallel viewers, and the voting device. Implicit variations were introduced due to the three different languages in Sweden, South Korea, and France. Although the obtained Mean Opinion Scores are comparable, slight differences occur in function of the video degradations and the viewing distance. An analysis on the statistical differences obtained between the MOS of the video sequences revealed that obtaining an equivalent number of differences may require more observers in some viewing conditions. It was also seen that the alignment of the meaning of the attributes used in Absolute Category Rating in different languages may be beneficial. Statistical analysis was performed showing influence of the viewing distance on votes and MOS results.
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| 7. |
- Ellinor, Patrick T., et al.
(författare)
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Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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| 8. |
- Engelke, Ulrich, et al.
(författare)
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Modelling Saliency Awareness for Objective Video Quality Assessment
- 2010
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Konferensbidrag (refereegranskat)abstract
- Existing video quality metrics do usually not take into consideration that spatial regions in video frames are of varying saliency and thus, differently attract the viewer's attention. This paper proposes a model of saliency awareness to complement existing video quality metrics, with the aim to improve the agreement of objectively predicted quality with subjectively rated quality. For this purpose, we conducted a subjective experiment in which human observers rated the annoyance of videos with transmission distortions appearing either in a salient region or in a non-salient region. The mean opinion scores confirm that distortions in salient regions are perceived much more annoying. It is shown that application of the saliency awareness model to two video quality metrics considerably improves their quality prediction performance.
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| 9. |
- Evans, Alistair R., et al.
(författare)
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The maximum rate of mammal evolution
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:11, s. 4187-4190
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Tidskriftsartikel (refereegranskat)abstract
- How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.
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| 10. |
- Falklöf, Olle
(författare)
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Photochemical properties of phytochrome and firefly luciferase chromophores: A theoretical study
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This licentiate thesis presents computational chemistry studies on photochemical properties of phytochrome and firefly luciferase chromophores.Phytochromes are bilin-containing proteins that based on the ambient light environment regulate a number of physiological and developmental processes in bacteria, cyanobacteria, fungi and plants. From the viewpoint of computational modeling, however, only a few studies have been devoted to these systems. In this thesis, two systematic studies comparing calculated and experimental UV-vis spectra of bilin chromophores in protein and solution environments are presented. The rst study focuses on how hybrid quantum mechanics/molecular mechanics methods are best applied to calculate absorption spectra of a bacteriophytochrome. The second study, in turn, investigates the performance of a number of quantum chemical methods in calculating absorption and emission spectra of sterically locked bilin chromophores.Firefly luciferase catalyzes a chemical reaction in which the electronically excited oxyluciferin is formed and subsequently emits light. Depending on the conditions, oxyluciferin can exist in a number of dierent chemical forms. To date, there is no consensus regarding which of these that most signicantly contributes to the light emission. In this thesis, the most probable form of the light emitter is predicted by calculating excited-state pKE and pKa values, in aqueous solution, of the various equilibrium reactions relevant for the oxyluciferin system.
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