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- 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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- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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- Qiao, Yuanhua, et al.
(författare)
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Pyrolysis Kinetic Study and Reaction Mechanism of Epoxy Glass Fiber Reinforced Plastic by Thermogravimetric Analyzer (TG) and TG–FTIR (Fourier-Transform Infrared) Techniques
- 2020
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Ingår i: Polymers. - : MDPI. - 2073-4360. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- TG–FTIR combined technology was used to study the degradation process and gas phase products of epoxy glass fiber reinforced plastic (glass fiber reinforced plastic) under the atmospheres of high purity nitrogen. The pyrolysis characteristics of epoxy glass fiber reinforced plastic were measured under different heating rates (5, 10, 15, 20 °C min−1) from 25 to 1000 °C. The thermogravimetric analyzer (TG) and differential thermogravimetric analyzer (DTG) curves show that the initial temperature, terminal temperature, and temperature of maximum weight loss rate in the pyrolysis reaction phase all move towards high temperature, as the heating rate increases. Epoxy glass fiber reinforced plastic has two stages of thermal weightlessness. The temperature range of the first stage of weight loss is 290–460 °C. The second stage is 460–1000 °C. The above two weight loss stages are caused by pyrolysis of the epoxy resin matrix, and the glass fiber will not decompose. The dynamic parameters of glass fiber reinforced plastic were obtained through the Kissinger-Akahira-Sunose (KAS), Flynn–Wall-Ozawa (FWO) and advanced Vyazovkin methods in model-free and the Coats–Redfern (CR) method in model fitting. FTIR spectrum result shows that the main components of the product gas are CO2, H2O, carbonyl components, and aromatic components during its pyrolysis.
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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Zhao, Shu-Na, et al.
(författare)
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Insights into thermochemistry, kinetics, and pyrolysis behavior of green gas generator 5- aminotetrazole by experiment and theoretical methods
- 2023
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Ingår i: Case Studies in Thermal Engineering. - : Elsevier Ltd. - 2214-157X. ; 49
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Tidskriftsartikel (refereegranskat)abstract
- Green gas generator 5-aminotetrazole(5-AT) has been widely used as a kind of energetic material with excellent properties, and it is crucial to understand its pyrolysis process and mechanism. The present study comprehensively investigated the thermochemistry, kinetics, and pyrolysis mechanism of green gas generator 5-AT, using a combination of experimental analysis and theoretical calculation. Thermogravimetric analysis (TGA) and fourier transform infrared spectroscopy (FTIR) were used to investigate the pyrolysis behavior of 5AT and energy barriers of transition states for different pyrolysis paths of three isomers of 5AT were also calculated at a high and reliable level of theory CCSD(T)/cc-pvtz. The results showed that the pyrolysis of 5-AT had five reaction stages and kinetic parameters in each stage were determined by Kissinger method and Criado method. Furthermore, the elimination of N2 from the tetrazole ring occurred before that of HN3, and N2 elimination had lower energy than HN3 elimination for 1-hydrogen-5-aminotetrazole and 2-hydrogen-5-aminotetrazole, but HN3 elimination had lower energy for 5-iminotetrazole. The results of the study provide useful insights into the pyrolysis mechanism and kinetics of 5-AT and could contribute to its efficient utilization in various applications.
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