| 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. |
- Li, Jian-Fang, et al.
(författare)
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Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:3, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. Materials and methods. Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, alpha alpha-smooth muscle actin (alpha alpha-SMA) and transforming growth factor-beta beta 1 (TGF-beta beta 1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. Results. Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group (p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group (p < 0.01). The expression of alpha alpha-SMA and TGF-beta beta 1 in HDg was less than that in the fibrosis group and LDg (p < 0.01). Conclusion. Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation.
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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. |
- Ma, Tao, et al.
(författare)
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Genomic insights into salt adaptation in a desert poplar
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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| 5. |
- Mithoefer, Kai, et al.
(författare)
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Guidelines for the design and conduct of clinical studies in knee articular cartilage repair: International cartilage repair society recommendations based on current scientific evidence and standards of clinical care
- 2011
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 2, s. 100-121
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project. © The Author(s) 2011.
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| 6. |
- Yao, Chen, et al.
(författare)
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A High-Resolution Time-to-Digital Converter Based on Parallel Delay Elements
- 2012
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Ingår i: ISCAS 2012 - 2012 IEEE International Symposium on Circuits and Systems. - : IEEE Solid-State Circuits Society. - 9781467302180 ; , s. 3158-3161
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Konferensbidrag (refereegranskat)abstract
- This paper presents a flash-type Time to Digital Converter (TDC) based on parallel delay elements in 65-nm CMOS process technology. By using parallel delay elements the conversion resolution of the TDC becomes equal to the difference of delay elements rather than the delay time of each element. A Sensed Amplifier Flip Flop (SAFF) ensures narrow sampling window. Operating at 1.2-V supply, this TDC shows 3ps resolution with 0.5LSB of INL and 0.33LSB of DNL respectively and consumes average power 442 mu W.
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| 7. |
- Yao, Mingguang, et al.
(författare)
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Confined adamantane molecules assembled to one dimension in carbon nanotubes
- 2011
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Ingår i: Carbon. - : Elsevier BV. - 0008-6223 .- 1873-3891. ; 49:4, s. 1159-1166
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Tidskriftsartikel (refereegranskat)abstract
- We have encapsulated adamantane (C10H16) in single- and multi-walled carbon nanotubes. Adamantane is a high symmetry cage like molecule with point group symmetry T-d and can be considered as a hydrogen-terminated diamond fragment. We confirmed and identified the successful filling by high resolution transmission electron microscopy, C-13 nuclear magnetic resonance, infrared and Raman spectroscopy. C-13 nuclear magnetic resonance of the adamantane filled nanotubes reveals that the adamantane molecules stop rotating after encapsulation. A blue-shift of the Raman active radial breathing modes of the carbon nanotubes supports this and suggests a significant interaction between encapsulated adamantane molecules and the single wall nanotubes. The encapsulated adamantane molecules exhibit red shifted infrared C-H vibration modes which we assign to a slight elongation of the C-H bonds. We observe both a nanotube diameter dependence of the adamantane filling ratio and a release rate of adamantane from the CNTs that depends on the CNT diameters.
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| 8. |
- Zhang, Jian, 1978, et al.
(författare)
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Examinations on closure models of conditionally filtered LES
- 2011
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Ingår i: Kung Cheng Je Wu Li Hsueh Pao/Journal of Engineering Thermophysics. - 0253-231X. ; 32:2, s. 357-359
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Tidskriftsartikel (refereegranskat)abstract
- The DNS and the conditionally filtered LES (CFLES) were combined to examine the validity of the linear-diffusion approximation and the first-order closure in CFLES equation. The linear-diffusion approximation was applied to closing transport term in mixture-fraction space in CFLES equation, and the first-order closure was used in closing conditionally filtered reaction source term. The first two order moments of filtered mass-fraction of the reactant were obtained by using CFLES and were closed to results of the DNS, which well examined the validity of the approximations mentioned above.
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| 9. |
- Zhang, Xiao-Dong, et al.
(författare)
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Establishment and assessments of a new model for the postoperative fatigue syndrome by major small intestinal resection in rats
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:11, s. 1302-1309
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Postoperative fatigue syndrome (POFS) is a general and main complication after surgery. However, there is no stable and standardized animal model for POFS. The aim of the present study was to establish a rodent model of POFS by small intestinal resection, with POFS evaluated by acknowledged physical and behavioral methods. Material and Methods. Forty-two Sprague-Dawley rats were randomly divided into four groups according to the length of a "middle" small intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70% groups, with corresponding lengths of small intestinal resections. Following surgery, the general state of health was evaluated. Tail suspension test, open field test and Morris water maze test were used to evaluate the degree of POFS. Serum albumin, transferrin, prealbumin and fibronectin were measured to assess the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Results. As compared with the other three groups, the 70% small intestinal resection group showed the worst general state of health, decreased strength of the tail suspension test and decreased score of Morris water maze test (p < 0.05) after operation. All rats in whom the small intestinal resection was done demonstrated a certain degree of malnutrition and behavior of depression, and the 70% resection group had the lowest levels of transferrin, prealbumin and fibronectin as compared with the other groups (p < 0.05), as well as decreased SOD and increased MDA in serum (p < 0.05). Conclusions. Resection of 70% of the small intestine resulted in typical characteristics of POFS. As this procedure is simple, stable and easily reproducible, it may serve as a model for research on POFS.
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| 10. |
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