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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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| 4. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 5. |
- Daneshjou, Roxana, et al.
(författare)
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Working toward precision medicine : Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges
- 2017
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 38:9, s. 1182-1192
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype-phenotype relationships.
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| 7. |
- Peng, Ningxin, et al.
(författare)
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Platelet mitochondrial DNA methylation : A novel biomarker for myocardial infarction – A preliminary study
- 2023
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Ingår i: International Journal of Cardiology. - 0167-5273.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Platelet activation and thrombus formation play critical roles in the pathogenesis of myocardial infarction (MI). In addition to their role in energy production, platelet mitochondria also regulate cellular functions related to apoptosis, oxidative stress, and inflammation. Epigenetic modifications of platelet mitochondrial DNA (mtDNA) may influence platelet function and are believed to be an important factor in MI. Therefore, the aim of this study was to investigate the differences in platelet mtDNA methylation levels between MI patients and controls. Methods: The present study utilized propensity score matching to generate 45 multivariate matched apparently healthy controls for 45 patients with newly-onset acute MI. Platelet mtDNA methylation levels were assessed through bisulfite-PCR pyrosequencing and compared between the two groups, with further adjustments made in the sensitivity analysis. Results: Among the measured mitochondrial genes (MT-COX1, MT-COX2, MT-COX3, MT-ND5, MT-ATP6 and tRNA_Leu), patients with MI exhibited statistically significant differences in mtDNA methylation levels as compared to matched controls. Specifically, higher levels of mtDNA methylation were observed in MT-COX1, MT-COX3, and tRNA_Leu, while a lower level was observed in MT-ATP6 (all p < 0.0001). These results remained robust in the sensitivity analysis. Conclusion: Our study demonstrated significant variations in platelet mtDNA methylation levels between patients with MI and controls. Platelet mtDNA methylation may serve as a novel biomarker for MI. This observation also provided some insights into the etiology of MI.
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| 8. |
- Sun, Fengbo, et al.
(författare)
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1,5-Diiodocycloctane: a cyclane solvent additive that can extend the exciton diffusion length in thick film organic solar cells
- 2024
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Ingår i: Energy and Environmental Sciences. - 1754-5692 .- 1754-5706. ; 17:5, s. 1916-1930
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Tidskriftsartikel (refereegranskat)abstract
- The short exciton diffusion length associated with most state-of-the-art organic semiconductors used in organic solar cells (OSCs) imposes severe limits on the exciton transport in the larger donor/acceptor domains and the exciton dissociation at the interface, which hinder further improvements in the power conversion efficiencies (PCE) of the thick-film devices. In this study, a new cyclane, 1,5-diiodocycloctane (DICO), was employed as a solvent additive to effectively extend the exciton LD within the bulk-heterojunction blend, which can function with the multiple photovoltaic materials system. Due to the great enhancement of molecular stacking and exclusively large domain sizes of photovoltaic materials with the assistance of the DICO additive, the trap density in devices is significantly reduced, thereby nearly doubling the LD in the thick film OSCs. Notably, the DICO-processed PM6/L8-BO-based OSC showed high thickness tolerance for the bulk-heterojunction (BHJ) layer, delivering a high PCE of 19.1% in the case of a 110 nm thick film and still maintaining an excellent PCE of 17.2% in the case of a 300 nm thick film. Crucially, a noticeably increased stability of the multiple materials system was observed in the DICO-processed OSCs. These findings enrich the additive family with new cyclane systems to extend the exciton LD in thick film OSCs with high performance.
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| 10. |
- Chen, Gang, et al.
(författare)
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EDF-VD Scheduling of Flexible Mixed-Criticality System With Multiple-Shot Transitions
- 2018
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Ingår i: IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems. - 0278-0070 .- 1937-4151. ; 37:11, s. 2393-2403
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Tidskriftsartikel (refereegranskat)abstract
- The existing mixed-criticality (MC) real-time task models assume that once any high-criticality task overruns, all high-criticality jobs execute up to their most pessimistic WCET estimations simultaneously in a one-shot manner. This is very pessimistic in the sense of unnecessary resource overbooking. In this paper, we propose a more generalized mixed-critical real-time task model, called flexible MC model with multiple-shot transitions (FMC-MST), to address this problem. In FMC-MST, high-criticality tasks can transit multiple intermediate levels to handle less pessimistic overruns independently and to nonuni-formly scale the deadline on each level. We develop a run-time schedulability analysis for FMC-MST under EDF-VD scheduling, in which a better tradeoff between the penalties of low-criticality tasks and the overruns of high-criticality tasks is achieved to improve the service quality of low-criticality tasks. We also develop a resource optimization technique to find resource-efficient level-insertion configurations for FMC-MST task systems under MC timing constraints. Experiments demonstrate the effectiveness of FMC-MST compared with the state-of-the-art techniques.
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