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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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| 3. |
- Kim, Joon Tae, et al.
(author)
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Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial : Rationale and design
- 2023
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In: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 18:8, s. 1015-1020
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Journal article (peer-reviewed)abstract
- Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.
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| 4. |
- Jeon, Jae Bum, et al.
(author)
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Photo-annealed amorphous titanium oxide for perovskite solar cells
- 2019
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In: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 11:41, s. 19488-19496
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Journal article (peer-reviewed)abstract
- Electron selective layers are important to the efficiency, stability and hysteresis of perovskite solar cells. Photo-annealing is a low-cost, roll-to-roll-compatible process that can be applied to the post-treatment fabrication of sol-gel based metal oxide layers. Here, we fabricate an amorphous titanium oxide electron selective layer at a low temperature in a dry atmosphere using a UV light annealing system and compare it with a thermal annealing process. Active oxygen species are created by using UV light to promote hydrolysis and condense the TiO2 precursor, which removes organic ligands effectively. The photo-annealed TiO2-based perovskite solar cell has a power conversion efficiency of 19.37% without hysteresis.
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| 5. |
- Lee, Hyun-Seob, et al.
(author)
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Foxa2 and Nurr1 Synergistically Yield A9 Nigral Dopamine Neurons Exhibiting Improved Differentiation, Function, and Cell Survival
- 2010
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In: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 28:3, s. 501-512
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Journal article (peer-reviewed)abstract
- Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs) is prerequisite for precursor/stem cell-based therapy of Parkinson's disease (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription factor that can drive DA neuron differentiation from non-dopaminergic NPCs in vitro. However, Nurr1 alone neither induces full neuronal maturation nor expression of proteins found specifically in midbrain DA neurons. In addition, Nurr1 expression is inefficient in inducing DA phenotype expression in NPCs derived from certain species such as mouse and human. We show here that Foxa2, a forkhead transcription factor whose role in midbrain DA neuron development was recently revealed, synergistically cooperates with Nurr1 to induce DA phenotype acquisition, midbrain-specific gene expression, and neuronal maturation. Thus, the combinatorial expression of Nurr1 and Foxa2 in NPCs efficiently yielded fully differentiated nigral (A9)-type midbrain neurons with clearly detectable DA neuronal activities. The effects of Foxa2 in DA neuron generation were observed regardless of the brain regions or species from which NPCs were derived. Furthermore, DA neurons generated by ectopic Foxa2 expression were more resistant to toxins. Importantly, Foxa2 expression resulted in a rapid cell cycle exit and reduced cell proliferation. Consistently, transplantation of NPCs transduced with Nurr1 and Foxa2 generated grafts enriched with midbrain-type DA neurons but reduced number of proliferating cells, and significantly reversed motor deficits in a rat PD model. Our findings can be applied to ongoing attempts to develop an efficient and safe precursor/stem cell-based therapy for PD. STEM CELLS 2010; 28: 501-512
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| 6. |
- Gabrielsson, Erik, et al.
(author)
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Autonomous Microcapillary Drug Delivery System Self-Powered by a Flexible Energy Harvester
- 2021
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In: Advanced Materials Technologies. - : Wiley-Blackwell. - 2365-709X. ; 6:11
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Journal article (peer-reviewed)abstract
- Implantable bioelectronic devices pave the way for novel biomedical applications operating at high spatiotemporal resolution, which is crucial for neural recording and stimulation, drug delivery, and brain-machine interfaces. Before successful long-term implantation and clinical applications, these devices face a number of challenges, such as mechanical and operational stability, biocompatibility, miniaturization, and powering. To address two of these crucial challenges-miniaturization and powering-the development and characterization of an electrophoretic drug delivery device, manufactured inside fused quartz fibers (outer diameter of 125 mu m), which is self-powered by a flexible piezoelectric energy harvester, are reported. The resulting device-the first integration of piezoelectric charging with "iontronic" delivery-exhibits a high delivery efficiency (number of neurotransmitters delivered per charges applied) and a direct correlation between the piezoelectric charging and the amount delivered (number of dynamic bends versus pmols delivered).
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| 7. |
- Jeong, Heesu, et al.
(author)
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Room-Temperature-Grown amorphous Indium-Tin-Silicon-Oxide thin film as a new electron transporting layer for perovskite solar cells
- 2022
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In: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 581
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Journal article (peer-reviewed)abstract
- We report the amorphous quaternary oxide, indium-tin-silicon-oxide (ITSO), thin film as a new electron transport layer (ETL) for perovskite solar cells (PSCs). ITSO thin films are grown by magnetron co-sputtering indium-tin-oxide (ITO) and silicon oxide (SiO2) on commercial transparent conducting oxide (TCO) thin films at room temperature. As Si content increases (0-53.8 at%) the optical bandgap increases by approximately 1.3 eV and the electrical resistivity increases by six orders mainly because of the carrier concentration decrease. Consequently, the ITSO electronic structure depends largely on Si content. PSCs employing ITSO thin films as ETLs were fabricated to evaluate the effect of Si content on device performances. Si content influenced the shunt and series resistance. The optimized device was obtained using an ITSO film with 33.0 at% Si content, exhibiting 14.50% power-conversion efficiency. These results demonstrate that ITSO films are promising for developing efficient PSCs by optimizing the growing process and/or In/Sn/Si/O compositions. This approach can reduce PSC manufacturing process time and costs if ITO and ITSO are grown together by continuous sequential sputtering in a dual gun (ITO and SiO2) chamber.
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| 8. |
- Kim, Kwangwoo, et al.
(author)
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High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
- 2015
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:3
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Journal article (peer-reviewed)abstract
- Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
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