| 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. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 3. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 4. |
- Duan, Chen, et al.
(författare)
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Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease.
- 2010
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Ingår i: Arthritis and Rheumatism. - : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 62:3, s. 771-780
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage from patients with Kashin-Beck disease (KBD) versus those with primary knee osteoarthritis (OA).METHODS: The messenger RNA expression profiles of articular cartilage from patients with KBD, diagnosed according to the clinical criteria for KBD in China, were compared with those of cartilage from patients with OA, diagnosed according to the Western Ontario and McMaster Universities OA Index. Total RNA was isolated separately from 4 pairs of the KBD and OA cartilage samples, and the expression profiles were evaluated by Agilent 4x44k Whole Human Genome density oligonucleotide microarray analysis. The microarray data for selected transcripts were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification.RESULTS: For 1.2 x 10(4) transcripts, corresponding to 58.4% of the expressed transcripts, 2-fold changes in differential expression were revealed. Expression levels higher in KBD than in OA samples were observed in a mean + or - SD 6,439 + or - 1,041 (14.6 + or - 2.4%) of the transcripts, and expression levels were lower in KBD than in OA samples in 6,147 + or - 1,222 (14.2 + or - 2.8%) of the transcripts. After application of the selection criteria, 1.85% of the differentially expressed genes (P < 0.001 between groups) were detected. These included 233 genes, of which 195 (0.4%) were expressed at higher levels and 38 (0.08%) were expressed at lower levels in KBD than in OA cartilage. Comparisons of the quantitative RT-PCR data supported the validity of our microarray data.CONCLUSION: Differences between KBD and OA cartilage exhibited a similar pattern among all 4 of the pairs examined, indicating the presence of disease mechanisms, mainly chondrocyte matrix metabolism, cartilage degeneration, and apoptosis induction pathways, which contribute to cartilage destruction in KBD.
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| 5. |
- Fan, Liangdong, 1985-, et al.
(författare)
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High performance transition metal oxide composite cathode for low temperature solid oxide fuel cells
- 2012
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 203:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Low temperature solid oxide fuel cells (SOFCs) with metal oxide composite cathode on the ceria–carbonate composite electrolyte have shown promising performance. However, the role of individual elements or compound is seldom investigated. We report here the effect of the ZnO on the physico-chemical and electrochemical properties of lithiated NiO cathode. The materials and single cells are characterized by X-ray diffraction, scanning electron microscopy, DC polarization electrical conductivity, electrochemical impedance spectroscopy and fuel cell performance. The ZnO modified lithiated NiO composite materials exhibit smaller particle size and lower electrical conductivity than lithiated NiO. However, improved electro-catalytic oxygen reduction activity and power output are achieved after the ZnO modification. A maximum power density of 808 mW cm−2 and the corresponding interfacial polarization resistance of 0.22 Ω cm2 are obtained at 550 °C using ZnO modified cathode and 300 μm thick composite electrolyte. The single cell keeps reasonable stability over 300 min at 500 °C. Thus, ZnO modified lithiated NiO is a promising cathode candidate for low temperature SOFCs.
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| 6. |
- Fan, Liangdong, et al.
(författare)
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Understanding the electrochemical mechanism of the core-shell ceria-LiZnO nanocomposite in a low temperature solid oxide fuel cell
- 2014
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 2:15, s. 5399-5407
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Tidskriftsartikel (refereegranskat)abstract
- Ceria based solid solutions have been considered some of the best candidates to develop intermediate/low temperature solid oxide fuel cells (IT/LT-SOFCs, 600-800 degrees C). However, the barrier to commercialization has not been overcome even after numerous research activities due to its inherent electronic conduction in a reducing atmosphere and inadequate ionic conductivity at low temperatures. The present work reports a new type of all-oxide nanocomposite electrolyte material based on a semiconductor, Li-doped ZnO (LixZnO), and an ionic conductor, samarium doped ceria (SDC). This electrolyte exhibits superionic conductivity (>0.1 S cm(-1) over 300 degrees C), net-electron free and excellent electrolytic performances (400-630 mW cm(-2)) between 480 and 550 degrees C. Particularly, defects related to interfacial conduction and the intrinsic and extrinsic properties of ions are analysed. An internal or interfacial redox process on two-phase particles is suggested as a powerful methodology to overcome the internal short-circuit problem of ceria-based single phase materials and to develop new advanced materials for energy related applications. The combination of the above promising features makes the SDC-LiZnO nanocomposite a promising electrolyte for LTSOFCs.
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| 7. |
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| 8. |
- Jing, Yifu, et al.
(författare)
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Enhanced conductivity of SDC based nanocomposite electrolyte by spark plasma sintering
- 2014
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Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 39:26, s. 14391-14396
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Tidskriftsartikel (refereegranskat)abstract
- Recently, ceria-based nanocomposites have been considered as promising electrolyte candidates for low-temperature solid oxide fuel cells (LTSOFC) due to their dual-ion conduction and excellent performance. However, the densification of these composites remains a great concern since the relative low density of the composite electrolyte is suspected to deteriorate the durability of fuel cell. In the present study, the ionic conductivity of two kinds of SDC-based nanocomposite electrolytes processed by spark plasma sintering (SPS) method was investigated, and compared to that made by conventional cold pressing followed by sintering (normal processing way). The density of solid electrolyte can reach higher than 95% of the theoretical value after SPS processing, while the relative density of the electrolyte pellets by normal processing way can hardly approach 75%. The structure and morphology of the sintered pellets were characterized by XRD and SEM. The ionic conductivity of samples was measured by electrochemical impedance spectroscopy (EIS). The results showed that the ionic conductivity of the two kinds of electrolytes treated with SPS was significantly enhanced, compared with the electrolyte pellets processed through the conventional method. The profile of impedance curve of the electrolytes was altered as well. This study demonstrates that the conductivity of SDC based nanocomposite electrolyte can be further improved by adequate densification process.
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| 9. |
- Li, Shu-Ming, et al.
(författare)
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Microwave-assisted method for the synthesis of cellulose-based composites and their thermal transformation to Mn2O3
- 2013
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Ingår i: Industrial crops and products (Print). - : Elsevier BV. - 0926-6690 .- 1872-633X. ; 43, s. 751-756
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the synthesis of inorganic materials using cellulose as a template by thermal treatment of the precursor. Cellulose-based composites have been successfully fabricated by an efficient microwave-assisted method. The influences of heating time on the phases and shape of the precursor were investigated. Mn2O3 materials were obtained by thermal treatment of the precursor at 600 degrees C for 3 h in air. The morphology of cellulose composites was preserved after thermal transformation to form Mn2O3. The products were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectrometry (FTIR), energy-dispersive X-ray spectra (EDS). scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential thermal analysis (DTA). A rapid microwave-assisted method with the thermal post-treatment provides a promising route for the fabrication of inorganic materials using natural polymer as a template.
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| 10. |
- Luo, Zhixun, et al.
(författare)
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Potential-induced Raman behavior of individual (R)-di-2-naphthylprolinol molecules on a Ag-modified Ag electrode
- 2011
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Ingår i: Journal of Raman Spectroscopy. - : Wiley. - 0377-0486 .- 1097-4555. ; 42:5, s. 951-957
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Tidskriftsartikel (refereegranskat)abstract
- The applicability of surface-enhanced Raman spectroscopy is demonstrated to probe the adsorption behavior of individual molecules on a Ag electrode. High-quality SERS spectra of (R)-di-2-naphthylprolinol (DNP) were obtained from ultradilute solutions (10(-12) M) on the Ag-nanoparticle-modified Ag electrode, which is attributed to the high electromagnetic (EM) effect of the SERS-active system as well as to the strong adsorption and interaction of DNP molecules with Ag. The stable SERS spectra present remarkable potential dependence, which gives evidence for the behavior of individual DNP molecules on the Ag surface. Based on statistical analysis for the probability of DNP molecules located in 'hot spots', we propose an SERS mechanism for individual molecules in the electrode system, in combination with the hot-spot model and orientation of the probemolecules.
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