| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 2. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
-
Application of LA-ICP-MS for meso-scale chloride profiling in concrete
- 2013
-
Ingår i: Materials and Structures/Materiaux et Constructions. - : Springer Science and Business Media LLC. - 1359-5997 .- 1871-6873. ; 46:8, s. 1369-1381
-
Tidskriftsartikel (refereegranskat)abstract
- Chloride represents a major risk for reinforced concrete structures because at a certain concentration, it can promote depassivation of the steel bars and initiate corrosion. Therefore it is important to be able to measure the chloride content in concrete. In this paper the application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for the study of chlorides in concrete is proposed. This scanning technique enables quick multi-element profiling, directly at the sample without the need for further preparation, within a range of sub-millimetre (meso-scale) resolution and with low limits of detection. Optimization of the operating conditions was performed in pressed concrete powder pellets. Linearity of the calibration was verified and limits of detection below 0.05 wt% of cement were determined. Chlorine, calcium and iron distributions were studied in cement based materials of increasing heterogeneity (paste, mortar and concrete). This technique is furthermore proposed for the study of the chloride induced corrosion process, by following element distributions along the concrete-steel interface at the time of depassivation.
|
|
| 3. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
-
Chloride analysis in concrete by LA-ICP-MS
- 2011
-
Ingår i: Advances in Construction Materials through Science and Engineering. ; RILEM PRO 79, s. 137-
-
Konferensbidrag (refereegranskat)abstract
- Chloride induced corrosion is the main problem affecting the durability of reinforced concrete structures. Therefore, the ability to measure chlorides in cementitious materials is of great importance. In this paper, we propose the application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for the determination of the total chloride content in concrete, highlighting the potential of the technique for overcoming two main difficulties: the time consuming depth profiling and the representativeness of the sampling procedures in concrete at the interface with steel. Portland cement concrete powder pellets were used for calibration purposes and the accuracy of the chloride determination is verified by the analysis of certified reference materials. Experimental conditions were adjusted in order to optimize the detection limit which was found to be of 0.011 wt%. Using fly ash and slag cement concretes, the influence of the matrix was assessed by comparing the results from LA-ICP-MS measurements to those obtained by potentiometric titration. The method was applied for chloride profiling along the concrete-steel interface of a specimen subjected to chloride exposure, showing good reproducibility within the calibration range.
|
|
| 4. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
-
CHLORIDE CONTENTS AT THE CONCRETE-STEEL INTERFACE
- 2010
-
Ingår i: Advances in Concrete Strutural Durability - Proceedings of the 2nd International Conference on Durability of Concrete Structures ICDCS2010, 24-26 November 2010, Hokkaido University, Sapporo, Japan, edited by Hiroshi Yokota, Takafumi Sugiyama and Tamon Ueda, Hokkaido University Press. - 9784832903609 ; , s. 275-284
-
Konferensbidrag (refereegranskat)abstract
- The composition and microstructure of the concrete-steel interface influences the criticalchloride content (Ccr) for initiation of pitting corrosion and can differ from the conditions inthe bulk concrete. This paper describes the development of a methodology for chlorideprofiling along the interface by means of LA-ICP-MS. SEM-EDS and XRD techniques wereused for semi-quantitative analysis of Ccr, microstructure characterization of the pittingpositions and distribution and composition of the corrosion products. A range of chloridelevels along the interface was measured by means of LA-ICP-MS showing good agreementwith the results from EDS analysis. A number of interface defects were found to influencepitting corrosion. Several Fe(III) oxy-hydroxides, including akaganeite, were identified. XRDanalysis suggested the existence of FeCl2. These corrosion products tended to accumulate atthe aggregate-paste interface and in air voids at the cement paste.
|
|
| 5. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
-
Chloride profiles along the concrete-steel interface
- 2013
-
Ingår i: International Journal of Structural Engineering. - 1758-7328 .- 1758-7336. ; 4:1/2, s. 100-112
-
Tidskriftsartikel (refereegranskat)abstract
- The composition and microstructure of the concrete-steelinterface influences the critical chloride content for initiation of pitting corrosion and these characteristics may differ from those of the bulk concrete. This paper describes the development of a methodology for chloride profiling along the interface by means of LA-ICP-MS. For semi-quantitative analysis, microstructure characterisation of the pitting positions and distribution and composition of the corrosion products, SEM-EDS and XRD techniques wereemployed. The results indicate that along the interface a range of chloride levels can be expected. These varied between 0.15–1.5 wt% of concrete with higher levels around the active corrosion sites. Good agreement has been foundbetween the results from LA-ICP-MS and EDS techniques. Interface defects strongly influenced the pitting corrosion. Several Fe(III) oxy-hydroxides accumulated at the aggregate-paste interface and in air voids at the cementpaste. XRD analysis suggested the presence of akaganeite and FeCl2 (rokuhnite).
|
|
| 6. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
-
Critical Conditions for Depassivation of Steel in Concrete: Interface Chloride Profiles
- 2011
-
Ingår i: Nordic Concrete Research. ; Publication No. 43, s. 115-118
-
Konferensbidrag (refereegranskat)abstract
- This paper describes an ongoing research project that aims to improve the knowledge and understanding of the critical conditions for depassivation of steel by studying the micro/meso-scale chloride profiles along the steel-concrete interface and correlating these with aspects of its microstructure and composition.
|
|
| 7. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
-
Critical Conditions for Depassivation of Steel in Concrete: Interface Chloride Profiles and Steel Surface Condition
- 2012
-
Ingår i: Nordic Concrete Research. - 0800-6377. ; 45, s. 111-123
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The composition and macrostructure of the concrete-steel interface and the surface finish of the steel are fundamental for the chloride induced corrosion initiation in reinforced concrete, with direct influence in the chloride threshold values (Cth). In this paper these characteristics were examined for vertically cast samples immersed in salt solution. After depassivation, the specimens were open for visual examination. Corrosion always initiated at the front side and surface defects were found to influence the corrosion onset. Chloride, calcium and iron profiles along the interface were drawn by means of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and higher chloride contents were measured around active corroding areas.
|
|
| 8. |
- Estrada, Karol, et al.
(författare)
-
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
|
|
| 9. |
- Gardner, Michael, et al.
(författare)
-
Gender and telomere length : Systematic review and meta-analysis
- 2014
-
Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 51, s. 15-27
-
Forskningsöversikt (refereegranskat)abstract
- Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions: Telomere length is longer in females thanmales, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. (C) 2013 Published by Elsevier Inc.
|
|
| 10. |
- Jiang, Jieying, et al.
(författare)
-
Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men.
- 2010
-
Ingår i: Clinica chimica acta. - : Elsevier BV. - 1873-3492 .- 0009-8981. ; 411:1-2, s. 53-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men. METHOD: Serum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged > or = 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using Tm-shift allele-specific PCR. RESULTS: SNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p<0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p=0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p=0.019 and p=1 x 10(-5), respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p=1 x 10(-5)). CONCLUSION: The genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.
|
|
