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- Reddy, A. Satyanarayana, et al.
(författare)
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Ultrathin titania coating for high-temperature stable SiO(2)/Pt nanocatalysts
- 2011
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 47, s. 8412-8414
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Tidskriftsartikel (refereegranskat)abstract
- The facile synthesis of silica supported platinum nanoparticles with ultrathin titania coating to enhance metal-support interactions suitable for high temperature reactions is reported, as thermal and structure stability of metal nanoparticles is important for catalytic reactions.
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- Yoo, Taekyeong, et al.
(författare)
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Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease.
- 2021
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 75:3, s. 514-523
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) poses an impending clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype.We recruited 125 Korean biopsy-proven NAFLD patients and healthy individuals and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed SNPs. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean NAFLD individuals was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models.The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in NAFLD patients homozygous for the non-reference allele of rs2291702, compared to no-NAFLD subjects with the same genotype (P = 4.79 × 10-6). This change was replicated in an additional 162 individuals, yielding a combined P-value of 8.05 × 10-8 from a total of 245 NAFLD patients and 48 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing ER stress, and exacerbated NAFLD diet-induced liver fibrosis in mice. However, overexpression of AGXT2 reversely attenuated liver fibrosis and steatosis as well.We implicate a new molecular role of AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD.Elucidating causal genes for NAFLD has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 biopsy-proven NAFLD and no-NAFLD Korean individuals and an additional 162 individuals for replication, we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of NAFLD causal genes that act on the basis of genotype.
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- Gabrielsson, Erik, et al.
(författare)
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Autonomous Microcapillary Drug Delivery System Self-Powered by a Flexible Energy Harvester
- 2021
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Ingår i: Advanced Materials Technologies. - : Wiley-Blackwell. - 2365-709X. ; 6:11
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Tidskriftsartikel (refereegranskat)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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- Jung, Chang Hoon, et al.
(författare)
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The seasonal characteristics of cloud condensation nuclei (CCN) in the arctic lower troposphere
- 2018
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 70:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Cloud Condensation Nuclei (CCN) concentration and aerosol size distributions in the Arctic were collected during the period 2007-2013 at the Zeppelin observatory (78.91 degrees N, 11.89 degrees E, 474 masl). Annual median CCN concentration at a supersaturation (SS) of 0.4% show the ranges of 45 approximate to 81cm(-3). The monthly median CCN number density varied between 17cm(-3) in October 2007 and 198cm(-3) in March, 2008. The CCN spectra parameters C (83cm(-3)) and k (0.23) were derived. In addition, calculated annual median value of hygroscopicity parameter is 0.46 at SS of 0.4%. Particle number concentration of accumulation mode from aerosol size distribution measurements are well correlated with CCN concentration. The CCN to CN>10 nm (particle number concentration larger than 10nm in diameter) ratio shows a maximum during March and minimum during July. The springtime high CCN concentration is attributed to high load of accumulation mode aerosol transported from the mid-latitudes, known as Arctic Haze. CCN concentration remains high also during Arctic summer due to the source of new CCN through particle formation followed by consecutive aerosol growth. Lowest aerosol as well as CCN number densities were observed during Arctic autumn and early winter when aerosol formation in the Arctic and long-range transport into the Arctic are not effective.
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- Lee, Hyun-Seob, et al.
(författare)
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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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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 28:3, s. 501-512
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Tidskriftsartikel (refereegranskat)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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- Park, Kwang-Hyun, et al.
(författare)
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RNA activation-independent DNA targeting of the Type III CRISPR-Cas system by a Csm complex
- 2017
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Ingår i: EMBO Reports. - : Wiley-VCH Verlagsgesellschaft. - 1469-221X .- 1469-3178. ; 18:5, s. 826-840
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Tidskriftsartikel (refereegranskat)abstract
- The CRISPR-Cas system is an adaptive and heritable immune response that destroys invading foreign nucleic acids. The effector complex of the Type III CRISPR-Cas system targets RNA and DNA in a transcription-coupled manner, but the exact mechanism of DNA targeting by this complex remains elusive. In this study, an effector Csm holocomplex derived from Thermococcus onnurineus is reconstituted with a minimalistic combination of Csm1(1)2(1)3(3)4(1)5(1), and shows RNA targeting and RNA-activated single-stranded DNA (ssDNA) targeting activities. Unexpectedly, in the absence of an RNA transcript, it cleaves ssDNA containing a sequence complementary to the bound crRNA guide region in a manner dependent on the HD domain of the Csm1 subunit. This nuclease activity is blocked by a repeat tag found in the host CRISPR loci. The specific cleavage of ssDNA without a target RNA suggests a novel ssDNA targeting mechanism of the Type III system, which could facilitate the efficient and complete degradation of foreign nucleic acids.
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