| 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. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 3. |
- Chen, Dingfu, et al.
(författare)
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Stitching interferometry of cylindrical surface
- 2022
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Ingår i: Optics and lasers in engineering. - : ELSEVIER SCI LTD. - 0143-8166 .- 1873-0302. ; 157
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Tidskriftsartikel (refereegranskat)abstract
- High resolution and high precision are advantages of measuring cylindrical objects employing stitching interferometry. However, due to errors in the cylinder position in a measurement procedure, it is difficult to ensure the accuracy of a macroscopic shape contour and surface waviness contour of the workpiece of the stitching results. To overcome this problem, we proposed a new strategy of stitching interferometry for cylindricity calibration. The measuring process is divided into two parts to measure the macroscopic shape and waviness contour, respectively. Finally, the two measurement results are merged to produce an accurate and complete 360 degrees form map. Besides, we build a two-dimensional Gaussian filter weighting function for a cylindrical profile according to its special shape characteristic. To express the stitching results more precisely, we provide the uncertainty map and power spectral density of the stitching results. An experiment is carried out by taking a ceramic plug gage as the workpiece. The results demonstrate the excellent performance of our method in analyzing the characteristic of the cylindrical profile and show good agreement with such by using cylindricity measuring instruments.
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| 4. |
- Chen, Fei'er, et al.
(författare)
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The effects of PM2.5 on asthmatic and allergic diseases or symptoms in preschool children of six Chinese cities, based on China, Children, Homes and Health (CCHH) project
- 2018
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 232, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- The urbanization and industrialization in China is accompanied by bad air quality, and the prevalence of asthma in Chinese children has been increasing in recent years. To investigate the associations between ambient PM2.5 levels and asthmatic and allergic diseases or symptoms in preschool children in China, we assigned PM2.5 exposure data from the Global Burden of Disease (GBD) project to 205 kindergartens at a spatial resolution of 0.1° × 0.1° in six cities in China (Shanghai, Nanjing, Chongqing, Changsha, Urumqi, and Taiyuan). A hierarchical multiple logistical regression model was applied to analyze the associations between kindergarten-level PM2.5 exposure and individual-level outcomes of asthmatic and allergic symptoms. The individual-level variables, including gender, age, family history of asthma and allergic diseases, breastfeeding, parental smoking, indoor dampness, interior decoration pollution, household annual income, and city-level variable-annual temperature were adjusted. A total of 30,759 children (average age 4.6 years, 51.7% boys) were enrolled in this study. Apart from family history, indoor dampness, and decoration as predominant risk factors, we found that an increase of 10 μg/m3 of the annual PM2.5 was positively associated with the prevalence of allergic rhinitis by an odds ratio (OR) of 1.20 (95% confidence interval [CI] 1.11, 1.29) and diagnosed asthma by OR of 1.10 (95% CI 1.03, 1.18). Those who lived in non-urban (vs. urban) areas were exposed to more severe indoor air pollution arising from biomass combustion and had significantly higher ORs between PM2.5 and allergic rhinitis and current rhinitis. Our study suggested that long-term exposure to PM2.5 might increase the risks of asthmatic and allergic diseases or symptoms in preschool children in China. Compared to those living in urban areas, children living in suburban or rural areas had a higher risk of PM2.5 exposure.
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| 5. |
- Chen, Zhihui, et al.
(författare)
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Exciton Polariton Contribution to the Stokes Shift in Colloidal Quantum Dots
- 2011
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:13, s. 5286-5293
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Tidskriftsartikel (refereegranskat)abstract
- We study the exciton polariton contribution to the Stokes shift in colloidal quantum dots (QDs). By detailed quantum mechanical description of light-matter interaction and temporal analysis of incident electromagnetic field across the QD using the finite-difference time-domain method, we have shown that the optical excitation of an exciton in the QD and its coupling with the excitation radiation (i.e., exciton polariton) induce strong variations in the dielectric constant of the QD which contribute significantly to the Stokes shift and cause modifications 50 in the absorption spectrum that agrees well with experiments.
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| 6. |
- Guo, Jianqiu, et al.
(författare)
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Associations of prenatal and childhood chlorpyrifos exposure with Neurodevelopment of 3-year-old children
- 2019
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 251, s. 538-546
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Tidskriftsartikel (refereegranskat)abstract
- Chlorpyrifos (CPF), an organophosphate insecticide, has been linked to adverse neurodevelopmental effects in animal studies. However, little is known about long-term neurotoxicity of early-life CPF exposure in humans. We aimed to evaluate the associations of both prenatal and early childhood CPF exposure with neurodevelopment of children. In this observational study based on Sheyang Mini Birth Cohort, pregnant women were recruited from an agricultural region between June 2009 and January 2010, and their children were followed up from birth to age three. Urinary 3,5,6-Trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, was quantified using large-volume-injection gas chromatography tandem mass spectrometry. Developmental quotients (DQs) of children in motor, adaptive, language, and social areas were assessed by trained pediatricians. Data from 377 mother-child pairs were used in the current study. Associations between CPF exposure and neurodevelopmental indicators were estimated using generalized linear models with adjustment for potential confounders. The median concentrations of TCPy in maternal and children's urine were 5.39 mu g/L and 5.34 mu g/L, respectively. No statistically significant association was found between maternal urinary TCPy concentrations and children neurodevelopment. While for postnatal exposure, we found lower motor area DQ score 0.61 [95% confidence interval (CI): -1.13, -0.09; p = 0.02] and social area DQ score 0.55 (95% CI: -1.07, -0.03; p = 0.04) per one-unit increase in the In-transformed childhood urinary TCPy concentrations. Further stratification by sex indicated that the inverse associations were only observed in boys, but not in girls. Our findings suggest that adverse neurodevelopmental effects were associated with early childhood CPF exposure, but not prenatal exposure. Additional longitudinal studies are needed to replicate these results and to further understand the toxicological mechanisms of CPF.
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| 7. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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| 8. |
- Makafe, Gaelle G., et al.
(författare)
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Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase
- 2019
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Ingår i: Cell Chemical Biology. - : CELL PRESS. - 2451-9456 .- 2451-9448. ; 26:8, s. 1187-
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Tidskriftsartikel (refereegranskat)abstract
- There is a great need for identification and development of new anti-tuberculosis drugs with novel targets. Recent drug-discovery efforts typically focus on identifying inhibitors but not activators that perturb metabolic enzymes' functions as a means to kill Mycobacterium tuberculosis (Mtb). Here, we describe a class of quinoline compounds, Z0933/Z0930, which kill Mtb by acting as activators of glutamate kinase (GK), a previously untargeted enzyme catalyzing the first step of proline biosynthesis. We further show that Z0933/Z0930 augment proline production and induce Mtb killing via proline-derived redox imbalance and production of reactive oxygen species. This work highlights the effectiveness of gain-of-function probes against Mtb and provides a framework for the discovery of next-generation allosteric activators of GK.
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| 9. |
- Wang, Hao, et al.
(författare)
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In-situ growth of low-dimensional perovskite-based insular nanocrystals for highly efficient light emitting diodes
- 2023
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Ingår i: Light. - : SPRINGERNATURE. - 2095-5545 .- 2047-7538. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices. However, judicious control of the grain growth for perovskite light emitting diodes is elusive due to its multiple requirements in terms of morphology, composition, and defect. Herein, we demonstrate a supramolecular dynamic coordination strategy to regulate perovskite crystallization. The combined use of crown ether and sodium trifluoroacetate can coordinate with A site and B site cations in ABX(3) perovskite, respectively. The formation of supramolecular structure retard perovskite nucleation, while the transformation of supramolecular intermediate structure enables the release of components for slow perovskite growth. This judicious control enables a segmented growth, inducing the growth of insular nanocrystal consist of low-dimensional structure. Light emitting diode based on this perovskite film eventually brings a peak external quantum efficiency up to 23.9%, ranking among the highest efficiency achieved. The homogeneous nano-island structure also enables high-efficiency large area (1 cm(2)) device up to 21.6%, and a record high value of 13.6% for highly semi-transparent ones.
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