| 1. |
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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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| 3. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 4. |
- Huang, Liping, et al.
(författare)
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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
- 2020
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 221, s. 136-145
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Tidskriftsartikel (refereegranskat)abstract
- The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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| 5. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 6. |
- Zhong, Jun, et al.
(författare)
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A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
- 2020
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 112:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
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| 7. |
- Bercovici, Antoine, et al.
(författare)
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Terrestrial paleoenvironment characterization across the Permian-Triassic boundary in South China
- 2015
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Ingår i: Journal of Asian Earth Sciences. - : Elsevier BV. - 1367-9120 .- 1878-5786. ; 98, s. 225-246
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Tidskriftsartikel (refereegranskat)abstract
- Well-preserved marine fossils in carbonate rocks permit detailed studies of the end-Permian extinction event in the marine realm. However, the rarity of fossils in terrestrial depositional environments makes it more challenging to attain a satisfactory degree of resolution to describe the biotic turnover on land. Here we present new sedimentological, paleontological and geochemical (X-ray fluorescence) analysis from the study of four terrestrial sections (Chahe, Zhejue, Mide and Jiucaichong) in Western Guizhou and Eastern Yunnan (Yangtze Platform, South China) to evaluate paleoenvironmental changes through the Permian-Triassic transition. Our results show major differences in the depositional environments between the Permian Xuanwei and the Triassic Kayitou formations with a change from fluvial-lacustrine to coastal marine settings. This change is associated with a drastic modification of the preservation mode of the fossil plants, from large compressions to small comminuted debris. Plant fossils spanning the Permian-Triassic boundary show the existence of two distinct assemblages: In the Xuanwei Formation, a Late Permian (Changhsingian) assemblage with characteristic Cathaysian wetland plants (mainly Gigantopteris dictyophylloides, Gigantonoclea guizhouensis, G. nicotianaefolia, G. plumosa, G. hallei, Lobatannularia heinanensis, L. cathaysiana, L. multifolia, Annularia pingloensis, A. shirakii, Paracalamites stenocostatus, Cordaites sp.) is identified. In the lowermost Kayitou Formation, an Early Triassic (Induan) Annalepis-Peltaspermum assemblage is shown, associated with very rare, relictual gigantopterids. Palynological samples are poor, and low yield samples show assemblages almost exclusively represented by spores. A similar to 1 m thick zone enriched in putative fungal spores was identified near the top of the Xuanwei Formation, including diverse multicellular forms, such as Reduviasporonites sp. This interval likely corresponds to the PTB "fungal spike" conventionally associated with land denudation and ecosystem collapse. While the floral turnover is evident, further studies based on plant diversity would be required in order to assess contribution linked to the end-Permian mass extinction versus local paleoenvironmental changes associated with the transition between the Xuanwei and Kayitou formations. (C) 2014 Elsevier Ltd. All rights reserved.
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| 8. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 9. |
- Cui, Ying, et al.
(författare)
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Carbon cycle perturbation expressed in terrestrial Permian–Triassic boundary sections in South China
- 2017
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Ingår i: Global and Planetary Change. - Amsterdam : Elsevier. - 0921-8181 .- 1872-6364. ; 148, s. 272-285
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Tidskriftsartikel (refereegranskat)abstract
- Stable isotopes of inorganic and organic carbon are commonly used in chemostratigraphy to correlatemarine andterrestrial sedimentary sequences based on the assumption that the carbon isotopic signature of the exogenic carbon pool dominates other sources of variability. Here, sediment samples fromfour Permian–Triassic boundary (PTB) sections ofwesternGuizhou and eastern Yunnan provinces in South China, representing a terrestrial tomarine transitional setting,were analyzed for δ13C of organic matter (δ13Corg). These valueswere subsequently compared to published δ13C values of carbonates (δ13Ccarb) from the Global Stratotype Section and Point at Meishan and many other marine and terrestrial sections. A similar isotopic trend evident through all four sections is characterized by a negative shift of 2–3‰ at the top of the Xuanwei Formation, where we tentatively place the PTB. This negative shift also corresponds to a turnover in the vegetation and the occurrence of fungal spores, which is generally interpreted as a proliferation of decomposers and collapse of complex ecosystems during the end-Permian mass extinction event. Moreover, the absolute values of δ13Corg are more extreme in the more distal (marine) deposits. The δ13Corg values for the studied sediments aremore variable compared to coeval δ13Ccarb records from marine records especially in the interval below the extinction horizon. We contend that the depositional environment influenced the δ13Corg values, but that the persisting geographic δ13Corg pattern through the extinction event across the four independent sections is an indication that the atmospheric δ13C signal left an indelible imprint on the geologic record related to the profound ecosystem change during the end-Permian extinction event.
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| 10. |
- Dai, Yi, et al.
(författare)
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Zn-doped CaFeO3 perovskite-derived high performed catalyst on oxygen reduction reaction in microbial fuel cells
- 2021
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Ingår i: Journal of Power Sources. - : ELSEVIER. - 0378-7753 .- 1873-2755. ; 489
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Tidskriftsartikel (refereegranskat)abstract
- Stable perovskite oxide is considered as a potential cathode for microbial fuel cells (MFCs). Herein, Zn is used as an effective element to modify the micro-structure and oxygen vacancy of perovskite to be a novel cathode catalyst. Physical characterizations show that due to partial volatilization at high temperature of Zn, perovskite forms hierarchically porous structures. Moreover, Zn is precipitated in electrochemical reaction to generate Zn vacancy in situ; thus, the active center of Fe has a superior interaction with oxygen-containing species, promoting the production of oxygen vacancy and forms a mixed valence state of Fe2+/Fe3+. The Zn-doped perovskite material CaFe0.7Zn0.3O3 exhibits remarkable oxygen reduction reaction (ORR) performances with outstanding onset potential (0.194 V vs. Ag/AgCl) and half-wave potential (-0.219 V vs. Ag/AgCl) under alkaline condition, which is better than Pt/C catalyst. Besides, CaFe0.7Zn0.3O3 shows an excellent four-electron pathway of ORR mechanism with remarkable corrosion resistance and stability, which enables a more reliable cathode electrocatalyst. The maximum power density of CaFe0.7Zn0.3O3 (892.10 +/- 90.79 mW m(-3)) testing on microbial fuel cell is comparable to the maximum power density (1012.86 +/- 84.03 mW m(-3)) of Pt/C. The findings of this work provide the feasibility of exploring inexpensive and high-performance cathode catalyst.
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