| 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. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 3. |
- Cai, Guan, et al.
(författare)
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Root exudates with low C/N ratios accelerate CO2 emissions from paddy soil
- 2022
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Ingår i: Land Degradation and Development. - : Wiley. - 1099-145X .- 1085-3278. ; 33:8, s. 1193-1203
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Tidskriftsartikel (refereegranskat)abstract
- Root exudates can significantly modify microbial activity and soil organic matter (SOM) mineralization. However, how root exudates and their C/N stoichiometric ratios control paddy soil C mineralization is poorly understood. This study used a mixture of glucose, oxalic acid, and alanine as root exudate mimics for three C/N stoichiometric ratios (CN6, CN10, and CN80) to explore the underlying mechanisms involved in SOM mineralization. The input of root exudates enhanced CO2 emissions by 1.8–2.3-fold that of soil with only C additions (C-only). Artificial root exudates with low C/N ratios (CN6 and CN10) increased the metabolic quotient (qCO2) by 12% over those with higher stoichiometric ratios (CN80 and C-only), suggesting a relatively high energy demand for microorganisms to acquire organic N from SOM by increasing N-hydrolase production. The increase of stoichiometric ratios of C- to N-hydrolase (β-1,4-glucosidase to β-1,4-N-acetyl glucosaminidase) promoted SOM degradation compared to those involved in organic C- and N- degradation, which had a significant positive correlation with qCO2. The stoichiometric ratios of microbial biomass (MBC/MBN) were positively correlated with C use efficiency, indicating root exudates with higher C/N ratios provide an undersupply of N for microorganisms that trigger the release of N-degrading extracellular enzymes. Our findings showed that the C/N stoichiometry of root exudates controlled SOM mineralization by affecting the specific response of the microbial biomass through the activity of C- and N-releasing extracellular enzymes to adjust the microbial C/N ratio.
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| 4. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 5. |
- Han, Ning, et al.
(författare)
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Rational design of Ruddlesden–Popper perovskite electrocatalyst for oxygen reduction to hydrogen peroxide
- 2022
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Ingår i: SusMat. - : Wiley. - 2766-8479 .- 2692-4552. ; 2:4, s. 456-465
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Tidskriftsartikel (refereegranskat)abstract
- Although the oxygen reduction process to hydrogen peroxide (H2O2) is a green option for H2O2 generation, the low activity and selectivity hindered the industry's process. In recent years, the electrochemical synthesis of H2O2 through a 2e– transfer method of oxygen reduction reaction (ORR) has piqued the interest of both academics and industry. Metal oxide catalysts have emerged as a novel family of electrochemical catalysts due to their unusual physical, chemical, and electrical characteristics. In this work, we first developed a Ruddlesden–Popper perovskite oxide (Pr2NiO4+δ) as a highly selective and active catalyst for 2e– ORR to produce H2O2. Molybdenum was introduced here to adjust the oxidation states of these transition metals with successful substitution into Ni-site to prepare Pr2Ni1-xMoxO4+δ, and the molybdenum substitution improves the H2O2 selectivity during the ORR process, in 0.1 M KOH, from 60% of Pr2NiO4+δ to 79% of Pr2Ni0.8Mo0.2O4+δ at 0.55 V versus RHE. A limiting H2O2 concentration of 0.24 mM for Pr2NiO4+δ and 0.42 mM for Pr2Ni0.8Mo0.2O4+δ was obtained at a constant current of 10 mA/cm2 using a flow-cell reactor using a gas-diffusion electrode.
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| 6. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 7. |
- Li, Cai, et al.
(författare)
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Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment
- 2014
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Ingår i: GigaScience. - 2047-217X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adelie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri]. Results: Phylogenetic dating suggests that early penguins arose similar to 60 million years ago, coinciding with a period of global warming. Analysis of effective population sizes reveals that the two penguin species experienced population expansions from similar to 1 million years ago to similar to 100 thousand years ago, but responded differently to the climatic cooling of the last glacial period. Comparative genomic analyses with other available avian genomes identified molecular changes in genes related to epidermal structure, phototransduction, lipid metabolism, and forelimb morphology. Conclusions: Our sequencing and initial analyses of the first two penguin genomes provide insights into the timing of penguin origin, fluctuations in effective population sizes of the two penguin species over the past 10 million years, and the potential associations between these biological patterns and global climate change. The molecular changes compared with other avian genomes reflect both shared and diverse adaptations of the two penguin species to the Antarctic environment.
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| 8. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 9. |
- Wang, Yuchen, et al.
(författare)
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Field observations of C2 and C3 organosulfates and insights into their formation mechanisms at a suburban site in Hong Kong
- 2023
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Ingår i: SCIENCE OF THE TOTAL ENVIRONMENT. - 0048-9697 .- 1879-1026. ; 904
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Tidskriftsartikel (refereegranskat)abstract
- Organosulfates (OSs) are formed from volatile organic compounds (VOCs) and their oxidation products in the presence of sulfate particles. While OSs represent an important component in secondary organic aerosol, the knowledge of their formation driving force, mechanisms, and environmental impact remain inadequately understood. In this study, we report ambient observations of C2-3 oxygenated VOCs derived OSs (C2-3 OSs) at a suburban location of Hong Kong during autumn 2016. The C2-3 OSs, including glycolaldehyde sulfate (GS), hydroxyacetone sulfate (HAS), glycolic acid sulfate (GAS), and lactic acid sulfate (LAS), were quantified/semiquantified using offline liquid chromatography-mass spectrometry analysis of aerosol filter samples. The average sum concentration of C2-3 OSs was 36 ng/m3. Correlation analysis revealed that sulfate, surface area, and liquid water content were important factors influencing C2-3 OS formation. Online measurement with an iodide High-Resolution Time-of-Flight Chemical-Ionization Mass Spectrometer (HR-ToF-CIMS) coupled with the Filter Inlet for Gases and AEROsols (FIGAERO) was also conducted to monitor C2-3 OSs, and their potential oxygenated VOC precursors in both gas-and particle-phase, and aerosol acidity tracer simultaneously. Our measurements support that glycolaldehyde/glyoxal, hydroxyacetone, glycolic acid/glyoxal, and lactic acid/ methylglyoxal are likely precursors for GS, HAS, GAS, and LAS, respectively. Additionally, we found strong correlation between C2-3 OSs and H3S2O8 , a marker for aerosol acidity, providing field observational evidence for acid-catalyzed formation of small OSs. Based on both online and offline measurements, acid-catalyzed formation mechanisms in particle/aqueous phase are proposed. Specifically, the unique structure of adjacent carbonyl and hydroxyl groups in the C2-3 oxygenated VOC precursors can facilitate the formation of (1) a five member ring intermediate via intramolecular hydrogen bond to react with sulfur trioxide through heterogenous reaction or (2) cyclic sulfate intermediate via particle-phase reaction with sulfuric acid to generate C2-3 OSs. These proposed mechanisms provide an alternative pathway for the liquid-phase production of C2-3 OSs.
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| 10. |
- Wang, Zhenqian, et al.
(författare)
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Northward migration of the East Asian summer monsoon northern boundary during the twenty-first century
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The northern fringe area of the East Asian summer monsoon (EASM) between arid and semiarid regions is a fragile eco-environment zone and ecological transition zone, and it is highly sensitive to climate change. Predicting the future migration of the northern boundary of the EASM is important for understanding future East Asian climate change and formulating of decisions on ecological protection and economic development in arid and semiarid regions. The reanalysis dataset and simulations of 23 models from the Coupled Models Intercomparison Project Phase 6 (CMIP6) were used to investigate the response of the boundary of the ESAM to the global warming. The multi-model ensemble showed a northwestward migration of the EASM northern boundary during the near-term (2020–2060) and late-term (2061–2099) of the twenty-first century under various Shared Socioeconomic Pathways (SSPs). The northern boundary migrated northwestward by 23–28 and 74–76 km in the near-term and late-term respectively, under SSP1-2.6, 2-4.5 and 3-7.0 and by ~ 44 km and ~ 107 km respectively during the near-term and late-term under SSP5-8.5. During the twenty-first century, under various SSPs, the surface of the East Asian subcontinent warmed more than the ocean, thereby increasing the contrast of near-surface temperature and sea level pressure in summer between the East Asian subcontinent and the surrounding oceans. In turn, the intensified land–sea thermal contrast reinforced the EASM meridional circulation and thus transported more moisture from the Indian Ocean into northern China. Additionally, a poleward migration and weakening of the East Asian subtropical westerly jet would also favor an increase in precipitation, eventually caused a northwestward migration of the EASM northern boundary. The results suggest that the arid and semiarid ecotone will become wetter, which could dramatically improve the eco-environment in the future.
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