| 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. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
- Liang, Qi, et al.
(författare)
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First-Principles Exploration of Hazardous Gas Molecule Adsorption on Pure and Modified Al60N60 Nanoclusters
- 2020
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we use the first-principles method to study in details the characteristics of the adsorption of hazardous NO2, NO, CO2, CO and SO2 gas molecules by pure and heteroatom (Ti, Si, Mn) modified Al60N60 nanoclusters. It is found that the pure Al60N60 cluster is not sensitive to CO. When NO2, NO, CO2, CO and SO2 are adsorbed on Al60N60 cluster'stop.b, edge.a(p), edge.a(h), edge.a(p) andedge.a(h) sites respectively, the obtained configuration is the most stable for each gas. Ti, Si and Mn atoms prefer to stay on the top sites of Al60N60 cluster when these heteroatoms are used to modify the pure clusters. The adsorption characteristics of above hazardous gas molecules on these hetero-atom modified nanoclusters are also revealed. It is found that when Ti-Al60N60 cluster adsorbs CO and SO2, the energy gap decreases sharply and the change rate of gap is 62% and 50%, respectively. The Ti-modified Al60N60 improves the adsorption sensitivity of the cluster to CO and SO2. This theoretical work is proposed to predict and understand the basic adsorption characteristics of AlN-based nanoclusters for hazardous gases, which will help and guide researchers to design better nanomaterials for gas adsorption or detection.
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| 5. |
- Nie, Xi, et al.
(författare)
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Structural Evolution of AlN Nanoclusters and the Elemental Chemisorption Characteristics : Atomistic Insight
- 2019
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- A theoretical insight into the structural evolution of AlN atomic clusters and the chemisorption of several common alloying elements on a large cluster has been performed in the framework of state-of-the-art density functional theory calculations. We report the findings that the longitudinal growth takes precedence during the early stage of structural evolution of small AlN clusters, when the longitudinal dimension becomes stable, the AlN cluster proceeds with cross-growth and blossoms into the large-size Al60N60. Upon the growth of clusters, the structures tend to become well-knit gradually. As for the evolution of electronic structures of AlN clusters through the HSE06 calculations, the density of states curves become more and more nondiscrete with the atomic structures evolving from small to large size and tend to resemble that of the Wurtzite AlN. The chemisorption characteristics of the large Al60N60 cluster towards different elements such as Al, N, Fe and Cu are also theoretically unveiled, in which it is interestingly found that the N and Cu atoms are likely to be adsorbed similarly at the growth edge position of the Al60N60 cluster and the density of states curves of these two chemisorption systems near the Fermi level also show some interesting similarities.
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| 6. |
- Nie, Xi, et al.
(författare)
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Theoretical prediction of a novel aluminum nitride nanostructure : Atomistic exposure
- 2019
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Ingår i: Ceramics International. - : ELSEVIER SCI LTD. - 0272-8842 .- 1873-3956. ; 45:17, s. 23690-23693
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Tidskriftsartikel (refereegranskat)abstract
- Aluminum nitride has significant prospect as a kind of ceramic material in applications such as semiconductors, sensors and other electronic devices. In this work, a novel AlN nanostructure is reported in terms of the optimized atomic structure, energetics, phonon dispersions and electronic structures employing the state-of-the-art Density functional theory (DFT). The interesting propeller-shaped AlN nanowire structure is determined with its detailed bond lengths and bond angles identified. In this structure, the orbital hybridization of Al and N atoms with coordination number of three is sp2, and hybridization of Al and N atoms with coordination number of four and five are sp3 and sp3d, respectively. The binding energy and work function of the novel AlN nanostructure are -4.855 eV and -5.326 eV, respectively. The charge distribution inside the novel structure has also been explored through the differential charge density and the Bader charge analysis. The nanostructure has a band gap of 2.5 eV with its deep electronic structure revealed. This theoretical study proposes a new type of AlN nanowire and will make guidance for experimentalists to design novel III-V group ceramic nanostructures for semiconductor or other functional applications.
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| 7. |
- Qian, Zhao, et al.
(författare)
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Atomistic Modeling of Various Doped Mg2NiH4 as Conversion Electrode Materials for Lithium Storage
- 2019
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Ingår i: Crystals. - : MDPI. - 2073-4352. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we have compared the potential applications of nine different elements doped Mg2NiH4 as conversion-type electrode materials in Li-ion batteries by means of state-of-the-art Density functional theory calculations. The electrochemical properties, such as specific capacity, volume change and average voltage, as well as the atomic and electronic structures of different doped systems have been investigated. The Na doping can improve the electrochemical capacity of the pristine material. Si and Ti doping can reduce the band gap and benefit the electronic conductivity of electrode materials. All of the nine doping elements can help to reduce the average voltage of negative electrodes and lead to reasonable volume changes. According to the computational screening, the Na, Si and Ti doping elements are thought to be promising to enhance the comprehensive properties of pure material. This theoretical study is proposed to encourage and expedite the development of metal-hydrides based lithium-storage materials.
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