| 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. |
- Ding, Yang, et al.
(författare)
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Artificial intelligence-assisted point-of-care testing system for ultrafast and quantitative detection of drug-resistant bacteria
- 2023
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Ingår i: SMARTMAT. - : WILEY. - 2766-8525.
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Tidskriftsartikel (refereegranskat)abstract
- As one of the major causes of antimicrobial resistance, beta-lactamase develops rapidly among bacteria. Detection of beta-lactamase in an efficient and low-cost point-of-care testing (POCT) way is urgently needed. However, due to the volatile environmental factors, the quantitative measurement of current POCT is often inaccurate. Herein, we demonstrate an artificial intelligence (AI)-assisted mobile health system that consists of a paper-based beta-lactamase fluorogenic probe analytical device and a smartphone-based AI cloud. An ultrafast broad-spectrum fluorogenic probe (B1) that could respond to beta-lactamase within 20 s was first synthesized, and the detection limit was determined to be 0.13 nmol/L. Meanwhile, a three-dimensional microfluidic paper-based analytical device was fabricated for integration of B1. Also, a smartphone-based AI cloud was developed to correct errors automatically and output results intelligently. This smart system could calibrate the temperature and pH in the beta-lactamase level detection in complex samples and mice infected with various bacteria, which shows the problem-solving ability in interdisciplinary research, and demonstrates potential clinical benefits.
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| 4. |
- Fan, Mei-Cen, et al.
(författare)
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Room-temperature extraction of individual elements from charged spent LiFePO4 batteries
- 2022
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Ingår i: Rare Metals. - : Springer. - 1001-0521 .- 1867-7185.
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Tidskriftsartikel (refereegranskat)abstract
- Recycling millions of metric tons of spent LiFePO4 batteries would benefit human health while reducing resource depletion and environmental pollution. However, recovering individual elements from the spent batteries without generating waste is challenging. Here, we present a distinctive approach for recycling spent LiFePO4 batteries at room temperature, where water is the only leaching agent consumed. FePO4 and lithium intercalated graphite act as a precursor material for selectively extracting lithium, iron, and phosphorus through charging the LiFePO4 batteries to the delithiated state. NaOH solution extracted Fe from FePO4 within 30 min and regenerated without consumption, similar to a catalyst. Under the optimal leaching conditions (1 mol·L−1 NaOH, 0.5 h, NaOH/Fe molar ratio of 4.5), Fe and P leaching efficiencies achieved 89.1% and 99.2%, respectively. The methodology reflected in this research reduced the material cost per kg cathode material to a fraction of previously published reports, only occupies 6.13% of previous reports. In addition, the method improved the battery recycling revenue calculated by the EverBatt model by 2.31 times and 1.94 times over pyrometallurgical and hydrometallurgical methods. The proposed method allows for the convenient recovery of the elemental components of spent LiFePO4 batteries.
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| 5. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 6. |
- 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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| 7. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 8. |
- 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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| 9. |
- Yu, Qian, et al.
(författare)
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Antibacterial Prenylated Acylphloroglucinols from Psorothamnus fremontii
- 2015
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 78:11, s. 2748-2753
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Tidskriftsartikel (refereegranskat)abstract
- Psorothatins A-C (1-3), three antibacterial prenylated acylphloroglucinol derivatives, were isolated from the native American plant Psorothamnus fremontii. They feature an unusual alpha,beta-epoxyketone functionality and a beta-hydroxy-alpha,beta-unsaturated ketone structural moiety. The latter forms a pseudo-six-membered heterocyclic ring due to strong intramolecular hydrogen bonding, as indicated by the long-range proton-carbon correlations in the NMR experiments. Psorothatin C (3) was the most active compound against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, with IC50 values in the range 1.4-8.8 mu g/mL. The first total synthesis of 3 described herein permits future access to structural analogues with potentially improved antibacterial activities.
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| 10. |
- Fu, Yunfei, et al.
(författare)
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Fundamental Characteristics of Tropical Rain Cell Structures as Measured by TRMM PR
- 2020
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Ingår i: Journal of Meteorological Research. - : Springer Science and Business Media LLC. - 2095-6037 .- 2198-0934. ; 34:6, s. 1129-1150
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Tidskriftsartikel (refereegranskat)abstract
- Rain cells are the most elementary unit of precipitation system in nature. In this study, fundamental geometric and physical characteristics of rain cells over tropical land and ocean areas are investigated by using 15-yr measurements of the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR). The rain cells are identified with a minimum bounding rectangle (MBR) method. The results indicate that about 50% of rain cells occur at length of about 20 km and width of 15 km. The proportion of rain cells with length > 200 km and width > 100 km is less than 1%. There is a a log-linear relationship between the mean length and width of rain cells. Usually, for the same horizontal geometric parameters, rain cells tend to be square horizontally and lanky vertically over land, while vertically squatty over ocean. The rainfall intensity of rain cells varies from 0.4 to 10 mm h(-1) over land to 0.4-8 mm h(-1) over ocean. Statistical results indicate that the occurrence frequency of rain cells decreases as the areal fraction of convective precipitation in rain cells increases, while such frequency remains almost invariant when the areal fraction of stratiform precipitation varies from 10% to 80%. The relationship between physical and geometric parameters of rain cells shows that the mean rain rate of rain cells is more frequently associated with the increase of their area, with the increasing rate over land greater than that over ocean. The results also illustrate that heavy convective rain rate prefers to occur in larger rain cells over land while heavy stratiform rain rate tends to appear in larger rain cells over ocean. For the same size of rain cells, the areal fraction and the contribution of convective precipitation are about 10%-15% higher over land than over ocean.
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