| 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. |
- 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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| 3. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 4. |
- Xu, Chao-Qun, et al.
(författare)
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Genome sequence of Malania oleifera, a tree with great value for nervonic acid production
- 2019
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Malania oleifera, a member of the Olacaceae family, is an IUCN red listed tree, endemic and restricted to the Karst region of southwest China. This tree's seed is valued for its high content of precious fatty acids (especially nervonic acid). However, studies on its genetic makeup and fatty acid biogenesis are severely hampered by a lack of molecular and genetic tools. Findings We generated 51 Gb and 135Gb of raw DNA sequences, using Pacific Biosciences (PacBio) single-molecule real-time and 10x Genomics sequencing, respectively. A final genome assembly, with a scaffold N50 size of 4.65 Mb and a total length of 1.51Gb, was obtained by primary assembly based on PacBio long reads plus scaffolding with 10x Genomics reads. Identified repeats constituted approximate to 82% of the genome, and 24,064 protein-coding genes were predicted with high support. The genome has low heterozygosity and shows no evidence for recent whole genome duplication. Metabolic pathway genes relating to the accumulation of long-chain fatty acid were identified and studied in detail. Conclusions Here, we provide the first genome assembly and gene annotation for M. oleifera. The availability of these resources will be of great importance for conservation biology and for the functional genomics of nervonic acid biosynthesis.
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| 5. |
- 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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| 6. |
- Lin, Fangyuan, 1996-, et al.
(författare)
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Seasonal to decadal variations of precipitation oxygen isotopes in northern China linked to the moisture source
- 2024
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Ingår i: npj Climate and Atmospheric Science. - 2397-3722. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A precise characterization of moisture source and transport dynamics over the inland margins of monsoonal China is crucial for understanding the climatic significance of precipitation oxygen isotope (δ18Op) variability preserved in the regional proxy archives. Here, we use a general circulation model with an embedded water-tagging module to quantify the role of moisture dynamics on the seasonal to decadal variations of δ18Op in northern China. Our data indicate that during the non-monsoon season, the δ18Op variability is dominated by the temperature effect. Conversely, in the summer monsoon season, the moisture contributions from the low-latitude land areas (LLA), the Pacific Ocean (PO), and the North Indian Ocean (NIO) override the temperature effect and influence the summer δ18Op. Intensified upstream convection along the NIO moisture transport pathway results in a more negative summer δ18Op compared to moisture transported from the PO and LLA regions. Our analysis shows a decadal shift in summer δ18Op around the mid-1980s, marking changes in the relative contribution of oceanic moisture from PO and NIO in response to changes in the atmospheric circulation patterns influenced by the Pacific Decadal Oscillation. We suggest that such decadal-scale δ18Op variability can be recorded in the natural archives from the region, which can provide valuable insights into understanding past climate variability.
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| 7. |
- Maitre, Léa, et al.
(författare)
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State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event
- 2022
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 168
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Tidskriftsartikel (refereegranskat)abstract
- The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.
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| 8. |
- Ngo, Debby, et al.
(författare)
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Proteomic profiling reveals novel biomarkers and pathways in yype 2 diabetes risk
- 2021
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .
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| 9. |
- Sheng, Rongrong, et al.
(författare)
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Does hot weather affect work-related injury? A case-crossover study in Guangzhou, China
- 2018
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 221:3, s. 423-428
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite increasing concerns about the health effects of climate change, the extent to which workers are affected by hot weather is not well documented. This study aims to investigate the association between high temperatures and work-related injuries using data from a large subtropical city in China. Methods: We used workers’ compensation claims to identify work-related injuries in Guangzhou, China during 2011–2012. To feature the heat effect, the study period was restricted to the warm seasons in Guangzhou (1 May-31 October). We conducted a time-stratified case-crossover study to examine the association between ambient outdoor temperatures, including daily maximum and minimum temperatures, and cases of work-related injury. The relationships were assessed using conditional Poisson regression models. Results: Overall, a total of 5418 workers’ compensation claims were included over the study period. Both maximum and minimum temperatures were significantly associated with work-related injuries, but associations varied by subgroup. One °C increase in maximum temperature was associated with a 1.4% (RR = 1.014, 95%CIs 1.012–1.017) increase in daily injury claims. Significant associations were seen for male and middle-aged workers, workers in small and medium-sized enterprises, and those working in manufacturing sector. And 1 °C increase in minimum temperature was associated with 1.7% (RR = 1.017, 95%CIs 1.012–1.021) increase in daily injury claims. Significant associations were observed for female and middle-aged workers, workers in large-sized enterprises, and those working in transport and construction sectors. Conclusions: We found a higher risk of work-related injuries due to hot weather in Guangzhou, China. This study provides important epidemiological evidence for policy-makers and industry that may assist in the formulation of occupational safety and climate adaptation strategies.
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| 10. |
- Wernstedt Asterholm, Ingrid, 1978, et al.
(författare)
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Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.
- 2014
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Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 20:1, s. 103-18
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin.
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