| 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. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 3. |
- Han, Yang, et al.
(författare)
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X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer
- 2012
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Ingår i: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 7:183
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHistone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).MethodsHDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.ResultsExpression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.ConclusionsX-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.
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| 4. |
- Hylander, Samuel, et al.
(författare)
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Induced tolerance expressed as relaxed behavioural threat response in millimetre-sized aquatic organisms
- 2014
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 281:1788, s. Article ID: 20140364-
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Tidskriftsartikel (refereegranskat)abstract
- Natural selection shapes behaviour in all organisms, but this is difficult to study in small, millimetre-sized, organisms. With novel labelling and tracking techniques, based on nanotechnology, we here show how behaviour in zooplankton (Daphnia magna) is affected by size, morphology and previous exposure to detrimental ultraviolet radiation (UVR). All individuals responded with immediate downward swimming to UVR exposure, but when released from the threat they rapidly returned to the surface. Large individuals swam faster and generally travelled longer distances than small individuals. Interestingly, individuals previously exposed to UVR (during several generations) showed a more relaxed response to UVR and travelled shorter total distances than those that were naive to UVR, suggesting induced tolerance to the threat. In addition, animals previously exposed to UVR also had smaller eyes than the naive ones, whereas UVR-protective melanin pigmentation of the animals was similar between populations. Finally, we show that smaller individuals have lower capacity to avoid UVR which could explain patterns in natural systems of lower migration amplitudes in small individuals. The ability to change behavioural patterns in response to a threat, in this case UVR, adds to our understanding of how organisms navigate in the ‘landscape of fear’, and this has important implications for individual fitness and for interaction strengths in biotic interactions.
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| 5. |
- Yang, Tao, et al.
(författare)
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Assessing the impact of human activities on hydrological and sediment changes (1953–2000) in nine major catchments of the Loess Plateau, China
- 2010
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Ingår i: Rivers Research and Applications. - : Wiley. - 1535-1459 .- 1535-1467. ; 26:3, s. 322-340
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Tidskriftsartikel (refereegranskat)abstract
- The Range of Variability Approach (RVA) is employed to investigate the variability and spatial patterns of hydrological and sediment changes (1953-2000) induced by intensified human activities, i.e. the implementation of water and soil conservation measures, in nine major catchments of the Loess Plateau, China. Results indicate that: (1) streamflow and sediment load regimes were greatly changed by the implementation of conservation measures; (2) similar spatial patterns of high hydrological and sediment changes resulting from the intensive implementation of conservation measures are observed in most catchments of the middle Yellow River. However, slightly different behaviours of changes exist due to the unique complexity of hydrological and sediment processes in this region and (3) the impacts of various conservation measures on hydrological and sediment processes are closely associated with the extent and types of these measures. Engineering works have a quite immediate impact on streamflow and sediment regimes. Considerable vegetation controls are recognized as additional important driving forces for high hydrological and sediment alterations among various soil conservation measures. In vegetation controls, afforestation is the major factor causing the changes of runoff and sediment processes in these nine catchments. The results of the current study will be greatly beneficial to the regional water resources management and restoration of eco-environmental system in the middle Yellow River basin characterized by intensified soil-conservation measures under the changing environment. Copyright (C) 2009 John Wiley & Sons, Ltd.
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| 6. |
- Yang, Tao, et al.
(författare)
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Regional flood frequency and spatial patterns analysis in the Pearl River Delta region using L-moments approach
- 2010
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Ingår i: Stochastic environmental research and risk assessment (Print). - : Springer Science and Business Media LLC. - 1436-3240 .- 1436-3259. ; 24:2, s. 165-182
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Tidskriftsartikel (refereegranskat)abstract
- The Pearl River Delta (PRD) has one of the most complicated deltaic drainage systems with probably the highest density of crisscross-river network in the world. This article presents a regional flood frequency analysis and recognition of spatial patterns for flood-frequency variations in the PRD region using the well-known index flood L-moments approach together with some advanced statistical test and spatial analysis methods. Results indicate that: (1) the whole PRD region is definitely heterogeneous according to the heterogeneity test and can be divided into three homogeneous regions; (2) the spatial maps for annual maximum flood stage corresponding to different return periods in the PRD region suggest that the flood stage decreases gradually from the riverine system to the tide dominated costal areas; (3) from a regional perspective, the spatial patterns of flood-frequency variations demonstrate the most serious flood-risk in the coastal region because it is extremely prone to the emerging flood hazards, typhoons, storm surges and well-evidenced sea-level rising. Excessive rainfall in the upstream basins will lead to moderate floods in the upper and middle PRD region. The flood risks of rest parts are identified as the lowest in entire PRD. In order to obtain more reliable estimates, the stationarity and serial-independence are tested prior to frequency analysis. The characterization of the spatial patterns of flood-frequency variations is conducted to reveal the potential influences of climate change and intensified human activities. These findings will definitely contribute to formulating the regional development strategies for policymakers and stakeholders in water resource management against the menaces of frequently emerged floods and well-evidenced sea level rising.
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| 7. |
- Zhang, Zhiqun, et al.
(författare)
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Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products
- 2014
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.
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| 8. |
- Ahlgren, Johan, et al.
(författare)
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Camouflaged or tanned: plasticity in freshwater snail pigmentation.
- 2013
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Ingår i: Biology letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 9:5, s. 4-20130464
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Tidskriftsartikel (refereegranskat)abstract
- By having phenotypically plastic traits, many organisms optimize their fitness in response to fluctuating threats. Freshwater snails with translucent shells, e.g. snails from the Radix genus, differ considerably in their mantle pigmentation patterns, with snails from the same water body ranging from being completely dark pigmented to having only a few dark patterns. These pigmentation differences have previously been suggested to be genetically fixed, but we propose that this polymorphism is owing to phenotypic plasticity in response to a fluctuating environment. Hence, we here aimed to assess whether common stressors, including ultraviolet radiation (UVR) and predation, induce a plastic response in mantle pigmentation patterns of Radix balthica. We show, in contrast to previous studies, that snails are plastic in their expression of mantle pigmentation in response to changes in UVR and predator threats, i.e. differences among populations are not genetically fixed. When exposed to cues from visually hunting fish, R. balthica increased the proportion of their dark pigmentation, suggesting a crypsis strategy. Snails increased their pigmentation even further in response to UVR, but this also led to a reduction in pattern complexity. Furthermore, when exposed to UVR and fish simultaneously, snails responded in the same way as in the UVR treatment, suggesting a trade-off between photoprotection and crypsis.
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| 9. |
- Chen, David, et al.
(författare)
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Hydrologic alteration along the Middle and Upper East River (Dongjiang) basin, South China : a visually enhanced mining on the results of RVA method
- 2010
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Ingår i: Stochastic environmental research and risk assessment (Print). - : Springer Science and Business Media LLC. - 1436-3240 .- 1436-3259. ; 24, s. 9-18
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a visually enhanced evaluation of the spatio-temporal patterns of the dam-induced hydrologic alteration in the middle and upper East River, south China over 1952-2002, using the range of variability approach (RVA) and visualization package XmdvTool. The impacts of climate variability on hydrological processes have been removed for wet and dry periods, respectively, so that we focus on the impacts of human activities (i.e., dam construction). The results indicate that: (1) along the East River, dams have greatly altered the natural flow regime, range condition and spatial variability; (2) six most remarkable indicators of hydrologic alteration induced by dam-construction are rise rate (1.16), 3-day maximum (0.91), low pulse duration (0.88), January (0.80), July (0.80) and February (0.79) mean flow of the East River during 1952-2002; and (3) spatiotemporal hydrologic alterations are different among three stations along Easter River. Under the influence of dam construction in the upstream, the degree of hydrologic changes from Lingxia, Heyuan to Longchuan station increases. This study reveals that visualization techniques for high-dimensional hydrological datasets together with RVA are beneficial for detecting spatio-temporal hydrologic changes.
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| 10. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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