| 1371. |
- Kraehling, J. R., et al.
(författare)
-
Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. © The Author(s) 2016.
|
|
| 1372. |
- Krasznahorkay, A., et al.
(författare)
-
Neutron-skin thickness from the study of the anti-analog giant dipole resonance
- 2012
-
Ingår i: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. - 9780735411036 ; 1491, s. 190-197
-
Konferensbidrag (refereegranskat)abstract
- The γ-decay of the anti-analog of the giant dipole resonance (AGDR) to the isobaric analog state has been measured following the p( 124Sn,n) reaction at a beam energy of 600 MeV/nucleon. The energy of the transition was also calculated with state-of-the-art self-consistent relativistic random-phase approximation (RPA) and turned out to be very sensitive to the neutronskin thickness (ΔRpn). By comparing the theoretical results with the measured one, the ΔRpn value for 124Sn was deduced to be 0.21 ± 0.07 fm, which agrees well with the previous results. The present method offers new possibilities for measuring the neutron-skin thicknesses of very exotic isotopes.
|
|
| 1373. |
|
|
| 1374. |
|
|
| 1375. |
|
|
| 1376. |
- Kristan, Matej, et al.
(författare)
-
The Sixth Visual Object Tracking VOT2018 Challenge Results
- 2019
-
Ingår i: Computer Vision – ECCV 2018 Workshops. - Cham : Springer Publishing Company. - 9783030110086 - 9783030110093 ; , s. 3-53
-
Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2018 is the sixth annual tracker benchmarking activity organized by the VOT initiative. Results of over eighty trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis and a “real-time” experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. A long-term tracking subchallenge has been introduced to the set of standard VOT sub-challenges. The new subchallenge focuses on long-term tracking properties, namely coping with target disappearance and reappearance. A new dataset has been compiled and a performance evaluation methodology that focuses on long-term tracking capabilities has been adopted. The VOT toolkit has been updated to support both standard short-term and the new long-term tracking subchallenges. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net).
|
|
| 1377. |
- Kroeger, Janine, et al.
(författare)
-
Circulating Fetuin-A and Risk of Type 2 Diabetes : A Mendelian Randomization Analysis
- 2018
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:6, s. 1200-1205
-
Tidskriftsartikel (refereegranskat)abstract
- Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
|
|
| 1378. |
- Kuderna, Lukas F. K., et al.
(författare)
-
A global catalog of whole-genome diversity from 233 primate species
- 2023
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
-
Tidskriftsartikel (refereegranskat)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
|
|
| 1379. |
- Kuderna, Lukas F. K., et al.
(författare)
-
Identification of constrained sequence elements across 239 primate genomes
- 2024
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
-
Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
|
|
| 1380. |
|
|
