| 1. |
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| 2. |
- 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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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 5. |
- You, Xiaohu, et al.
(författare)
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Towards 6G wireless communication networks: vision, enabling technologies, and new paradigm shifts
- 2021
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Ingår i: Science China Information Sciences. - : Science Press. - 1674-733X .- 1869-1919. ; 64:1
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Forskningsöversikt (refereegranskat)abstract
- The fifth generation (5G) wireless communication networks are being deployed worldwide from 2020 and more capabilities are in the process of being standardized, such as mass connectivity, ultra-reliability, and guaranteed low latency. However, 5G will not meet all requirements of the future in 2030 and beyond, and sixth generation (6G) wireless communication networks are expected to provide global coverage, enhanced spectral/energy/cost efficiency, better intelligence level and security, etc. To meet these requirements, 6G networks will rely on new enabling technologies, i.e., air interface and transmission technologies and novel network architecture, such as waveform design, multiple access, channel coding schemes, multi-antenna technologies, network slicing, cell-free architecture, and cloud/fog/edge computing. Our vision on 6G is that it will have four new paradigm shifts. First, to satisfy the requirement of global coverage, 6G will not be limited to terrestrial communication networks, which will need to be complemented with non-terrestrial networks such as satellite and unmanned aerial vehicle (UAV) communication networks, thus achieving a space-air-ground-sea integrated communication network. Second, all spectra will be fully explored to further increase data rates and connection density, including the sub-6 GHz, millimeter wave (mmWave), terahertz (THz), and optical frequency bands. Third, facing the big datasets generated by the use of extremely heterogeneous networks, diverse communication scenarios, large numbers of antennas, wide bandwidths, and new service requirements, 6G networks will enable a new range of smart applications with the aid of artificial intelligence (AI) and big data technologies. Fourth, network security will have to be strengthened when developing 6G networks. This article provides a comprehensive survey of recent advances and future trends in these four aspects. Clearly, 6G with additional technical requirements beyond those of 5G will enable faster and further communications to the extent that the boundary between physical and cyber worlds disappears.
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| 6. |
- Luo, Yiqi, et al.
(författare)
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Transient dynamics of terrestrial carbon storage : Mathematical foundation and its applications
- 2017
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:1, s. 145-161
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Tidskriftsartikel (refereegranskat)abstract
- Terrestrial ecosystems have absorbed roughly 30 % of anthropogenic CO2 emissions over the past decades, but it is unclear whether this carbon (C) sink will endure into the future. Despite extensive modeling and experimental and observational studies, what fundamentally determines transient dynamics of terrestrial C storage under global change is still not very clear. Here we develop a new framework for understanding transient dynamics of terrestrial C storage through mathematical analysis and numerical experiments. Our analysis indicates that the ultimate force driving ecosystem C storage change is the C storage capacity, which is jointly determined by ecosystem C input (e.g., net primary production, NPP) and residence time. Since both C input and residence time vary with time, the C storage capacity is time-dependent and acts as a moving attractor that actual C storage chases. The rate of change in C storage is proportional to the C storage potential, which is the difference between the current storage and the storage capacity. The C storage capacity represents instantaneous responses of the land C cycle to external forcing, whereas the C storage potential represents the internal capability of the land C cycle to influence the C change trajectory in the next time step. The influence happens through redistribution of net C pool changes in a network of pools with different residence times. Moreover, this and our other studies have demonstrated that one matrix equation can replicate simulations of most land C cycle models (i.e., physical emulators). As a result, simulation outputs of those models can be placed into a three-dimensional (3-D) parameter space to measure their differences. The latter can be decomposed into traceable components to track the origins of model uncertainty. In addition, the physical emulators make data assimilation computationally feasible so that both C flux-and pool-related datasets can be used to better constrain model predictions of land C sequestration. Overall, this new mathematical framework offers new approaches to understanding, evaluating, diagnosing, and improving land C cycle models.
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| 7. |
- Ning, Yuping, et al.
(författare)
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Optical simulation and preparation of novel Mo/ZrSiN/ZrSiON/SiO2 solar selective absorbing coating
- 2017
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Ingår i: Solar Energy Materials and Solar Cells. - : Elsevier BV. - 0927-0248 .- 1879-3398. ; 167, s. 178-183
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Tidskriftsartikel (refereegranskat)abstract
- A novel Mo/ZrSiN/ZrSiON/SiO2 solar selective absorbing coating has been investigated, which was prepared by magnetron sputtering on stainless steel substrate. A high solar absorptance of 0.94 and a low thermal emittance of 0.06 at 25 degrees C were achieved. By proportionally decreasing the thicknesses of the ZrSiN, ZrSiON and SiO2 layers, the thermal emittance at 500 degrees C was decreased significantly from 0.19 to 0.12 (Delta epsilon = 0.07) while keeping the solar absorptance unchanged. The coating also showed high thermal stability at 500 degrees C in vacuum, implying that it is a promising candidate for high temperature concentrated solar power (CSP) applications.
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| 8. |
- Tian, Yu-Peng, et al.
(författare)
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Investigations and facile synthesis of a series of novel multi-functional two-photon absorption materials
- 2007
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 17:34, s. 3646-3654
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Tidskriftsartikel (refereegranskat)abstract
- Six centrosymmetric D-(pi-A)(3) structural triphenylamine derivatives that can be used as two- photon photopolymerization and optical data storage chromophores, tris[ 4-( 4- pyridylethenyl) phenyl] amine ( 1), tris[ 4-( 2- pyridylethenyl) phenyl] amine ( 2), tris( 4- cyanoethenylphenyl) amine ( 3), tris[ 4- butylacrylatephenyl] amine ( 4), tris[ 4- methylacrylatephenyl] amine ( 5) and tris[ 4- acrylicethenylphenyl] amine ( 6), have been successfully synthesized via a triple palladium-catalyzed Heck coupling reaction, and the novel chromophores were fully characterized by elemental analysis, IR, (1)H-NMR and ESIMS. The structure for 3 was determined by single crystal X-ray diffraction study. One- and two-photon absorption and fluorescence in various solvents were experimentally investigated. Two-photon initiated polymerization microfabrication and optical data recording experiments were carried out under 780 nm laser radiation, and the possible polymerization mechanism is discussed based on theoretical calculations. All the six chromophores have relatively large two-photon absorption crosssections, and exhibit optical memory and highly efficient two-photon initiated polymerization abilities.
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| 9. |
- Xie, Xu-Qin, et al.
(författare)
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miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
- 2020
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Ingår i: MOLECULAR THERAPY-ONCOLYTICS. - : CELL PRESS. - 2372-7705. ; 17, s. 320-331
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Tidskriftsartikel (refereegranskat)abstract
- Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU] +leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC.
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| 10. |
- Daniel, Quentin, et al.
(författare)
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Rearranging from 6-to 7-coordination initiates the catalytic activity : An EPR study on a Ru-bda water oxidation catalyst
- 2017
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Ingår i: Coordination chemistry reviews. - : Elsevier. - 0010-8545 .- 1873-3840. ; 346, s. 206-215
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Tidskriftsartikel (refereegranskat)abstract
- The coordination of a substrate water molecule on a metal centered catalyst for water oxidation is a crucial step involving the reorganization of the ligand sphere. This process can occur by substituting a coordinated ligand with a water molecule or via a direct coordination of water onto an open site. In 2009, we reported an efficient ruthenium-based molecular catalyst, Ru-bda, for water oxidation. Despite the impressive improvement in catalytic activity of this type of catalyst over the past years, a lack of understanding of the water coordination still remains. Herein, we report our EPR and DFT studies on Ru-bda (triethylammonium 3-pyridine sulfonate)(2) (1) at its Ru-III oxidation state, which is the initial state in the catalytic cycle for the O-O bond formation. Our investigation suggests that at this III-state, there is already a rearrangement in the ligand sphere where the coordination of a water molecule at the 7th position (open site) takes place under acidic conditions (pH = 1.0) to form a rare 7-coordinated Ru-III species.
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| 11. |
- De Kauwe, Martin G., et al.
(författare)
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Forest water use and water use efficiency at elevated CO2: a model-data intercomparison at two contrasting temperate forest FACE sites
- 2013
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 19:6, s. 1759-1779
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Tidskriftsartikel (refereegranskat)abstract
- Predicted responses of transpiration to elevated atmospheric CO2 concentration (eCO2) are highly variable amongst process-based models. To better understand and constrain this variability amongst models, we conducted an intercomparison of 11 ecosystem models applied to data from two forest free-air CO2 enrichment (FACE) experiments at Duke University and Oak Ridge National Laboratory. We analysed model structures to identify the key underlying assumptions causing differences in model predictions of transpiration and canopy water use efficiency. We then compared the models against data to identify model assumptions that are incorrect or are large sources of uncertainty. We found that model-to-model and model-to-observations differences resulted from four key sets of assumptions, namely (i) the nature of the stomatal response to elevated CO2 (coupling between photosynthesis and stomata was supported by the data); (ii) the roles of the leaf and atmospheric boundary layer (models which assumed multiple conductance terms in series predicted more decoupled fluxes than observed at the broadleaf site); (iii) the treatment of canopy interception (large intermodel variability, 215%); and (iv) the impact of soil moisture stress (process uncertainty in how models limit carbon and water fluxes during moisture stress). Overall, model predictions of the CO2 effect on WUE were reasonable (intermodel =approximately 28%+/- 10%) compared to the observations (=approximately 30%+/- 13%) at the well-coupled coniferous site (Duke), but poor (intermodel =approximately 24%+/- 6%; observations =approximately 38%+/- 7%) at the broadleaf site (Oak Ridge). The study yields a framework for analysing and interpreting model predictions of transpiration responses to eCO2, and highlights key improvements to these types of models.
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| 12. |
- Huang, Hongyun, et al.
(författare)
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Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
- 2018
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:2, s. 310-324
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Forskningsöversikt (refereegranskat)abstract
- Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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| 13. |
- Walker, Anthony P., et al.
(författare)
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Comprehensive ecosystem model-data synthesis using multiple data sets at two temperate forest free-air CO2 enrichment experiments: Model performance at ambient CO2 concentration
- 2014
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Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953 .- 2169-8961. ; 119:5, s. 937-964
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Tidskriftsartikel (refereegranskat)abstract
- Free-air CO2 enrichment (FACE) experiments provide a remarkable wealth of data which can be used to evaluate and improve terrestrial ecosystem models (TEMs). In the FACE model-data synthesis project, 11 TEMs were applied to two decadelong FACE experiments in temperate forests of the southeastern U.S.the evergreen Duke Forest and the deciduous Oak Ridge Forest. In this baseline paper, we demonstrate our approach to model-data synthesis by evaluating the models' ability to reproduce observed net primary productivity (NPP), transpiration, and leaf area index (LAI) in ambient CO2 treatments. Model outputs were compared against observations using a range of goodness-of-fit statistics. Many models simulated annual NPP and transpiration within observed uncertainty. We demonstrate, however, that high goodness-of-fit values do not necessarily indicate a successful model, because simulation accuracy may be achieved through compensating biases in component variables. For example, transpiration accuracy was sometimes achieved with compensating biases in leaf area index and transpiration per unit leaf area. Our approach to model-data synthesis therefore goes beyond goodness-of-fit to investigate the success of alternative representations of component processes. Here we demonstrate this approach by comparing competing model hypotheses determining peak LAI. Of three alternative hypotheses(1) optimization to maximize carbon export, (2) increasing specific leaf area with canopy depth, and (3) the pipe modelthe pipe model produced peak LAI closest to the observations. This example illustrates how data sets from intensive field experiments such as FACE can be used to reduce model uncertainty despite compensating biases by evaluating individual model assumptions.
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| 14. |
- You, Fengzhi, et al.
(författare)
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Maternal mortality in Henan Province, China: changes between 1996 and 2009.
- 2012
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maternal deaths occur mostly in developing countries and the majority of them are preventable. This study analyzes changes in maternal mortality and related causes in Henan Province, China, between 1996 and 2009, in an attempt to provide a reliable basis for introducing effective interventions to reduce the maternal mortality ratio (MMR), part of the fifth Millennium Development Goal. Methods and Findings: This population-based maternal mortality survey in Henan Province was carried out from 1996 to 2009. Basic information was obtained from the health care network for women and children and the vital statistics system, from specially trained monitoring personnel in 25 selected monitoring sites and by household survey in each case of maternal death. This data was subsequently reported to the Henan Provincial Maternal and Child Healthcare Hospital. The total MMR in Henan Province declined by 78.4%, from 80.1 per 100 000 live births in 1996 to 17.3 per 100 000 live births in 2009. The decline was more pronounced in rural than in urban areas. The most common causes of maternal death during this period were obstetric hemorrhage (43.8%), pregnancy-induced hypertension (15.8%), amniotic fluid embolism (13.9%) and heart disease (8.0%). The MMR was higher in rural areas with lower income, less education and poorer health care. Conclusion: There was a remarkable decrease in the MMR in Henan Province between 1996 and 2009 mainly in the rural areas and MMR due to direct obstetric causes such as obstetric hemorrhage. This study indicates that improving the health care network for women, training of obstetric staff at basic-level units, promoting maternal education, and increasing household income are important interventional strategies to reduce the MMR further.
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| 15. |
- Zaehle, Soenke, et al.
(författare)
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Evaluation of 11 terrestrial carbon-nitrogen cycle models against observations from two temperate Free-Air CO2 Enrichment studies
- 2014
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Ingår i: New Phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 202:3, s. 803-822
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Tidskriftsartikel (refereegranskat)abstract
- We analysed the responses of 11 ecosystem models to elevated atmospheric [CO2] (eCO(2)) at two temperate forest ecosystems (Duke and Oak Ridge National Laboratory (ORNL) Free-Air CO2 Enrichment (FACE) experiments) to test alternative representations of carbon (C)-nitrogen (N) cycle processes. We decomposed the model responses into component processes affecting the response to eCO(2) and confronted these with observations from the FACE experiments. Most of the models reproduced the observed initial enhancement of net primary production (NPP) at both sites, but none was able to simulate both the sustained 10-yr enhancement at Duke and the declining response at ORNL: models generally showed signs of progressive N limitation as a result of lower than observed plant N uptake. Nonetheless, many models showed qualitative agreement with observed component processes. The results suggest that improved representation of above-ground-below-ground interactions and better constraints on plant stoichiometry are important for a predictive understanding of eCO(2) effects. Improved accuracy of soil organic matter inventories is pivotal to reduce uncertainty in the observed C-N budgets. The two FACE experiments are insufficient to fully constrain terrestrial responses to eCO(2), given the complexity of factors leading to the observed diverging trends, and the consequential inability of the models to explain these trends. Nevertheless, the ecosystem models were able to capture important features of the experiments, lending some support to their projections.
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| 16. |
- Zhang, Huai, et al.
(författare)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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Ingår i: Hepatology international. - 1936-0541.
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Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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| 17. |
- Ahlström, Anders, et al.
(författare)
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The dominant role of semi-arid ecosystems in the trend and variability of the land CO2 sink
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 348:6237, s. 895-899
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Tidskriftsartikel (refereegranskat)abstract
- The growth rate of atmospheric carbon dioxide (CO2) concentrations since industrialization is characterized by large interannual variability, mostly resulting from variability in CO2 uptake by terrestrial ecosystems (typically termed carbon sink). However, the contributions of regional ecosystems to that variability are not well known. Using an ensemble of ecosystem and land-surface models and an empirical observation-based product of global gross primary production, we show that the mean sink, trend, and interannual variability in CO2 uptake by terrestrial ecosystems are dominated by distinct biogeographic regions. Whereas the mean sink is dominated by highly productive lands (mainly tropical forests), the trend and interannual variability of the sink are dominated by semi-arid ecosystems whose carbon balance is strongly associated with circulation-driven variations in both precipitation and temperature.
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| 18. |
- Brenner, Darren R, et al.
(författare)
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Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia
- 2015
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 36:11, s. 1314-1326
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10−8) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10−7) and MTMR2 at 11q21 (rs10501831, P = 3.1×10−6) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10−7) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10−4 for KCNIP4, represented by rs9799795) and AC (P = 2.16×10−4 for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.
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| 19. |
- Desjardins, Kewin, et al.
(författare)
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Characterization of a back-illuminated CMOS camera for soft x-ray coherent scattering
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A commercial scientific camera has been adapted and characterized at the SOLEIL Synchrotron with the aim to improve the acquisition capabilities on the soft X-ray coherent scattering experimental station at SEXTANTS beamline. This device is equipped by the last generation of back side illuminated scientific CMOS (BSI-sCMOS) of 2048 by 2048 pixels of 11 μm2 able to acquire low noise images with a frame rate up to 48 Hz. The camera's performance measurements have been done and shows a good level of readout noise, a large full-well capacity, a medium dark current and a good homogeneity, respectively, 1.6 e- rms (in High Gain mode), 80 000 e- (in Low Gain mode),<5 e-/pixel/s and ∼ 1%. The quantum efficiency (QE) measurement has been performed at the soft x-ray branch of the METROLOGIE beamline and gives a relatively good agreement with the expected theoretical values. Finally, the demonstration of the camera's efficiency and of the gain in useful time measurement related to the high frame rate have been performed with a series of Airy patterns images compared with an image recorded using the standard BSI-CDD already in operation at the SEXTANTS beamline.
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| 20. |
- Griesmayer, E., et al.
(författare)
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Applications of single-crystal CVD diamond XBPM detectors with nanometre x-ray beams
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Measurements with a Diamond XBPM were carried out at the MAX IV Laboratory, Lund, Sweden, at the NanoMAX beam line. This was the first investigation of a Diamond XBPM detector with nanometre beams. The effect of diffusion, as well as the position resolution at the smallest available beam sizes were studied.
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| 21. |
- Jung, Martin, et al.
(författare)
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Compensatory water effects link yearly global land CO 2 sink changes to temperature
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 541:7638, s. 516-520
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Tidskriftsartikel (refereegranskat)abstract
- Large interannual variations in the measured growth rate of atmospheric carbon dioxide (CO 2) originate primarily from fluctuations in carbon uptake by land ecosystems. It remains uncertain, however, to what extent temperature and water availability control the carbon balance of land ecosystems across spatial and temporal scales. Here we use empirical models based on eddy covariance data and process-based models to investigate the effect of changes in temperature and water availability on gross primary productivity (GPP), terrestrial ecosystem respiration (TER) and net ecosystem exchange (NEE) at local and global scales. We find that water availability is the dominant driver of the local interannual variability in GPP and TER. To a lesser extent this is true also for NEE at the local scale, but when integrated globally, temporal NEE variability is mostly driven by temperature fluctuations. We suggest that this apparent paradox can be explained by two compensatory water effects. Temporal water-driven GPP and TER variations compensate locally, dampening water-driven NEE variability. Spatial water availability anomalies also compensate, leaving a dominant temperature signal in the year-to-year fluctuations of the land carbon sink. These findings help to reconcile seemingly contradictory reports regarding the importance of temperature and water in controlling the interannual variability of the terrestrial carbon balance. Our study indicates that spatial climate covariation drives the global carbon cycle response.
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| 22. |
- Li, Zhao, et al.
(författare)
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Non-uniform seasonal warming regulates vegetation greening and atmospheric CO2 amplification over northern lands
- 2018
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- The enhanced vegetation growth by climate warming plays a pivotal role in amplifying the seasonal cycle of atmospheric CO2 at northern lands (>50° N) since 1960s. However, the correlation between vegetation growth, temperature and seasonal amplitude of atmospheric CO2 concentration have become elusive with the slowed increasing trend of vegetation growth and weakened temperature control on CO2 uptake since late 1990s. Here, based on in situ atmospheric CO2 concentration records from the Barrow observatory site, we found a slowdown in the increasing trend of the atmospheric CO2 amplitude from 1990s to mid-2000s. This phenomenon was associated with the paused decrease in the minimum CO2 concentration ([CO2]min), which was significantly correlated with the slowdown of vegetation greening and growing-season length extension. We then showed that both the vegetation greenness and growing-season length were positively correlated with spring but not autumn temperature over the northern lands. Furthermore, such asymmetric dependences of vegetation growth upon spring and autumn temperature cannot be captured by the state-of-art terrestrial biosphere models. These findings indicate that the responses of vegetation growth to spring and autumn warming are asymmetric, and highlight the need of improving autumn phenology in the models for predicting seasonal cycle of atmospheric CO2 concentration.
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| 23. |
- Liu, Jin-ming, et al.
(författare)
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Mid-term effects of lung volume reduction surgery on pulmonary function in patients with chronic obstructive pulmonary disease
- 2007
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 120:8, s. 658-662
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Tidskriftsartikel (refereegranskat)abstract
- Background Now lung volume reduction surgery (LVRS) has become one of the most effective methods for the management of some cases of severe chronic obstructive pulmonary disease (COPD). We evaluated the mid-term effects of LVRS on pulmonary function in patients with severe COPD. Methods Ten male patients with severe COPD aged 38-70 years underwent LVRS and their pulmonary function was assessed before, 3 months and 3 years after surgery. The spirometric and gas exchange parameters included residual volume, total lung capacity, inspiratory capacity, forced vital capacity, forced expiratory volume in one second, diffusion capacity for CO, and arterial blood gas. A 6-minute walk distance (6MWD) test was performed. Results As to preoperative assessment, most spirometric parameters and 6MWD were significantly improved after 3 months and slightly 3 years after LVRS. Gas exchange parameters were significantly improved 3 months after surgery, but returned to the preoperative levels after 3 years. Conclusions LVRS may significantly improve pulmonary function in patients with severe COPD indicating for LVRS. Mid-term pulmonary function 3 years after surgery can be decreased to the level at 3 months after surgery. Three years after LVRS, lung volume and pulmonary ventilation function can be significantly improved, but the improvement in gas exchange function was not significant.
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| 24. |
- Luo, Yiqi, et al.
(författare)
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Matrix Approach to Land Carbon Cycle Modeling
- 2022
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 14:7
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Forskningsöversikt (refereegranskat)abstract
- Land ecosystems contribute to climate change mitigation by taking up approximately 30% of anthropogenically emitted carbon. However, estimates of the amount and distribution of carbon uptake across the world's ecosystems or biomes display great uncertainty. The latter hinders a full understanding of the mechanisms and drivers of land carbon uptake, and predictions of the future fate of the land carbon sink. The latter is needed as evidence to inform climate mitigation strategies such as afforestation schemes. To advance land carbon cycle modeling, we have developed a matrix approach. Land carbon cycle models use carbon balance equations to represent carbon exchanges among pools. Our approach organizes this set of equations into a single matrix equation without altering any processes of the original model. The matrix equation enables the development of a theoretical framework for understanding the general, transient behavior of the land carbon cycle. While carbon input and residence time are used to quantify carbon storage capacity at steady state, a third quantity, carbon storage potential, integrates fluxes with time to define dynamic disequilibrium of the carbon cycle under global change. The matrix approach can help address critical contemporary issues in modeling, including pinpointing sources of model uncertainty and accelerating spin-up of land carbon cycle models by tens of times. The accelerated spin-up liberates models from the computational burden that hinders comprehensive parameter sensitivity analysis and assimilation of observational data to improve model accuracy. Such computational efficiency offered by the matrix approach enables substantial improvement of model predictions using ever-increasing data availability. Overall, the matrix approach offers a step change forward for understanding and modeling the land carbon cycle.
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| 25. |
- Luo, Yiqi, et al.
(författare)
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Toward more realistic projections of soil carbon dynamics by Earth system models
- 2016
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 30:1, s. 40-56
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Tidskriftsartikel (refereegranskat)abstract
- Soil carbon (C) is a critical component of Earth system models (ESMs), and its diverse representations are a major source of the large spread across models in the terrestrial C sink from the third to fifth assessment reports of the Intergovernmental Panel on Climate Change (IPCC). Improving soil C projections is of a high priority for Earth system modeling in the future IPCC and other assessments. To achieve this goal, we suggest that (1) model structures should reflect real-world processes, (2) parameters should be calibrated to match model outputs with observations, and (3) external forcing variables should accurately prescribe the environmental conditions that soils experience. First, most soil C cycle models simulate C input from litter production and C release through decomposition. The latter process has traditionally been represented by first-order decay functions, regulated primarily by temperature, moisture, litter quality, and soil texture. While this formulation well captures macroscopic soil organic C (SOC) dynamics, better understanding is needed of their underlying mechanisms as related to microbial processes, depth-dependent environmental controls, and other processes that strongly affect soil C dynamics. Second, incomplete use of observations in model parameterization is a major cause of bias in soil C projections from ESMs. Optimal parameter calibration with both pool- and flux-based data sets through data assimilation is among the highest priorities for near-term research to reduce biases among ESMs. Third, external variables are represented inconsistently among ESMs, leading to differences in modeled soil C dynamics. We recommend the implementation of traceability analyses to identify how external variables and model parameterizations influence SOC dynamics in different ESMs. Overall, projections of the terrestrial C sink can be substantially improved when reliable data sets are available to select the most representative model structure, constrain parameters, and prescribe forcing fields.
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| 26. |
- Marcouille, O., et al.
(författare)
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Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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| 27. |
- Medlyn, Belinda E., et al.
(författare)
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Using models to guide field experiments : a priori predictions for the CO2 response of a nutrient- and water-limited native Eucalypt woodland
- 2016
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 22:8, s. 2834-2851
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Tidskriftsartikel (refereegranskat)abstract
- The response of terrestrial ecosystems to rising atmospheric CO2 concentration (Ca), particularly under nutrient-limited conditions, is a major uncertainty in Earth System models. The Eucalyptus Free-Air CO2 Enrichment (EucFACE) experiment, recently established in a nutrient- and water-limited woodland presents a unique opportunity to address this uncertainty, but can best do so if key model uncertainties have been identified in advance. We applied seven vegetation models, which have previously been comprehensively assessed against earlier forest FACE experiments, to simulate a priori possible outcomes from EucFACE. Our goals were to provide quantitative projections against which to evaluate data as they are collected, and to identify key measurements that should be made in the experiment to allow discrimination among alternative model assumptions in a postexperiment model intercomparison. Simulated responses of annual net primary productivity (NPP) to elevated Ca ranged from 0.5 to 25% across models. The simulated reduction of NPP during a low-rainfall year also varied widely, from 24 to 70%. Key processes where assumptions caused disagreement among models included nutrient limitations to growth; feedbacks to nutrient uptake; autotrophic respiration; and the impact of low soil moisture availability on plant processes. Knowledge of the causes of variation among models is now guiding data collection in the experiment, with the expectation that the experimental data can optimally inform future model improvements.
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| 28. |
- Norton, Alexander J., et al.
(författare)
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Estimating global gross primary productivity using chlorophyll fluorescence and a data assimilation system with the BETHY-SCOPE model
- 2019
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 16:15, s. 3069-3093
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents the assimilation of solar-induced chlorophyll fluorescence (SIF) into a terrestrial biosphere model to estimate the gross uptake of carbon through photosynthesis (GPP). We use the BETHY-SCOPE model to simulate both GPP and SIF using a process-based formulation, going beyond a simple linear scaling between the two. We then use satellite SIF data from the Orbiting Carbon Observatory-2 (OCO-2) for 2015 in the data assimilation system to constrain model biophysical parameters and GPP. The assimilation results in considerable improvement in the fit between model and observed SIF, despite a limited capability to fit regions with large seasonal variability in SIF. The SIF assimilation increases global GPP by 31% to 167±5 PgCyr-1 and shows an improvement in the global distribution of productivity relative to independent estimates, but a large difference in magnitude. This change in global GPP is driven by an overall increase in photosynthetic lightuse efficiency across almost all biomes and more minor, regionally distinct changes in APAR. This process-based data assimilation opens up new pathways to the effective utilization of satellite SIF data to improve our understanding of the global carbon cycle.
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| 29. |
- Plivelic, Tomás S., et al.
(författare)
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X-ray tracing, design and construction of an optimized optics scheme for CoSAXS, the small angle x-ray scattering beamline at MAX IV laboratory
- 2019
-
Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
-
Konferensbidrag (refereegranskat)abstract
- A novel optical design for a flexible SAXS beamline at a modern synchrotron has been implemented for the CoSAXS beamline at the 3GeV ring at the MAX TV Laboratory. The performance of the beamline has been simulated through combined ray tracing and wave propagation with the code xrt taking into account the low emittance and highly coherent beam of MAX TV and the short inter-optics distances of the beamline. The total photon flux is estimated to be 1012-1013 ph/s with the coherent flux portion up to 10 % at 7.1 keV. The inhomogeneities in the X-ray beam arising from use of real (non-idealised) mirror surfaces are also modelled using the measured slope profiles of the mirrors. Strategies to mitigate these inhomogeneities are discussed. The optical components for CoSAXS have been constructed and beamline commissioning will start in 2019.
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| 30. |
- Ren, Long Jun, et al.
(författare)
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Effect of conventional physiotherapy on pain and muscle stiffness in patients with low back pain assessed by a wireless hand-held tissue ultrasound palpation system (TUPS)
- 2019
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Ingår i: International Journal of Physical Medicine Rehabilitation. - : Omics Publishing Group. - 2329-9096. ; 7:2, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low back pain (LPB) is a common health problem. While physiotherapy can relieve pain and the muscle stiffness of patients with LBP was shown to be different from healthy people, few studies have investigated the effect of physiotherapy on back muscle stiffness in patients with LBP.Objective: To investigate the effect of a 5-day conventional physiotherapy treatment on muscle stiffness of patients with LBP using a newly developed wireless hand-held ultrasound probe.Methods: A total of ten patients with LBP participated in this study. They received customized conventional physiotherapy containing electrical therapy, traditional Chinese medicine, manipulation and wax therapy. The pain level was evaluated by the visual analogue scale, and the muscle stiffness was measured by a wireless hand-held tissue ultrasound palpation system. The muscle stiffness of left and right sides at L1 and L4 levels and pain level were evaluated in two conditions, including baseline and 5-day post treatments.Results and discussion: After receiving the treatment, the muscle stiffness of all tested low back regions increased significantly (p=0.040). The muscle stiffness at L4 level was significantly higher than that of L1 level (p=0.021). No significant difference of muscle stiffness between left and right sides was found. The correlation between the muscle stiffness and VAS score appeared to decrease after receiving the treatment (R2 changed from 0.3598 to 0.0533).Conclusion: A five-day conventional physiotherapy treatment could relieve the pain level and increase the muscle stiffness of patients with LBP as evaluated by a wireless hand-held ultrasound probe. The stiffness of back muscle at L4 level was significantly higher than that of L1 level in patients with LBP. The treatment may change the correlation between the muscle stiffness and VAS score at low back region.
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| 31. |
- Shi, Ying, et al.
(författare)
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Effects of low-molecular-weight polyols on the hydration status of the light-harvesting complex 2 from Rhodobacter sphaeroides 2.4.1
- 2021
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Ingår i: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-905X .- 1474-9092. ; 20:5, s. 627-637
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Tidskriftsartikel (refereegranskat)abstract
- Low-molecular-weight (MW) polyols are organic osmolytes influencing water activity. We have investigated the effects of polyol molecules (glycerol and sorbitol) on the optical and triplet excitation dynamics of light-harvesting complex 2 (LH2) from Rhodobacter (Rba.) sphaeroides in buffer-detergent solutions. The resonance Raman spectroscopy demonstrated that, on increasing glycerol and sorbitol volume fractions ranging from 0 to 80% (v/v) (accompanied by the decreasing water activities), the planar and all-trans conformation of carotenoids (Crts) remained unchanged, and the bacteriochlorophyll a (BChl) Qy absorption intensity decreased. The B850 fluorescence amplitude elevated in the 20–80% v/v sorbitol and 20–40% v/v glycerol solution, but decreased in 80% v/v glycerol solution. The change of 3[Crt*–BChl] interaction bands caused by 3Crt*–BChl interaction had no obvious correlation with water activities against polyol volume fractions, which are rationalized by the water activity sensitive of C- and N-termini of protein which binding with BChls. The results suggest that Rba. sphaeroides LH2 is more sensitive to low-molecular-weight polyols compared with that of the thermophiles purple bacterium Thermochromatium (Tch.) tepidum we had investigated before. Graphic abstract: [Figure not available: see fulltext.]
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| 32. |
- Tao, Feng, et al.
(författare)
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Convergence in simulating global soil organic carbon by structurally different models after data assimilation
- 2024
-
Ingår i: Global Change Biology. - 1354-1013 .- 1365-2486. ; 30:5
-
Tidskriftsartikel (refereegranskat)abstract
- Current biogeochemical models produce carbon–climate feedback projections with large uncertainties, often attributed to their structural differences when simulating soil organic carbon (SOC) dynamics worldwide. However, choices of model parameter values that quantify the strength and represent properties of different soil carbon cycle processes could also contribute to model simulation uncertainties. Here, we demonstrate the critical role of using common observational data in reducing model uncertainty in estimates of global SOC storage. Two structurally different models featuring distinctive carbon pools, decomposition kinetics, and carbon transfer pathways simulate opposite global SOC distributions with their customary parameter values yet converge to similar results after being informed by the same global SOC database using a data assimilation approach. The converged spatial SOC simulations result from similar simulations in key model components such as carbon transfer efficiency, baseline decomposition rate, and environmental effects on carbon fluxes by these two models after data assimilation. Moreover, data assimilation results suggest equally effective simulations of SOC using models following either first-order or Michaelis–Menten kinetics at the global scale. Nevertheless, a wider range of data with high-quality control and assurance are needed to further constrain SOC dynamics simulations and reduce unconstrained parameters. New sets of data, such as microbial genomics-function relationships, may also suggest novel structures to account for in future model development. Overall, our results highlight the importance of observational data in informing model development and constraining model predictions.
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| 33. |
- Tao, Feng, et al.
(författare)
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Microbial carbon use efficiency promotes global soil carbon storage
- 2023
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 981-985
-
Tidskriftsartikel (refereegranskat)abstract
- Soils store more carbon than other terrestrial ecosystems. How soil organic carbon (SOC) forms and persists remains uncertain, which makes it challenging to understand how it will respond to climatic change. It has been suggested that soil microorganisms play an important role in SOC formation, preservation and loss. Although microorganisms affect the accumulation and loss of soil organic matter through many pathways, microbial carbon use efficiency (CUE) is an integrative metric that can capture the balance of these processes. Although CUE has the potential to act as a predictor of variation in SOC storage, the role of CUE in SOC persistence remains unresolved. Here we examine the relationship between CUE and the preservation of SOC, and interactions with climate, vegetation and edaphic properties, using a combination of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning and meta-analysis. We find that CUE is at least four times as important as other evaluated factors, such as carbon input, decomposition or vertical transport, in determining SOC storage and its spatial variation across the globe. In addition, CUE shows a positive correlation with SOC content. Our findings point to microbial CUE as a major determinant of global SOC storage. Understanding the microbial processes underlying CUE and their environmental dependence may help the prediction of SOC feedback to a changing climate.
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| 34. |
- Walker, Anthony P., et al.
(författare)
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Predicting long-term carbon sequestration in response to CO2 enrichment: How and why do current ecosystem models differ?
- 2015
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 29:4, s. 476-495
-
Tidskriftsartikel (refereegranskat)abstract
- Large uncertainty exists in model projections of the land carbon (C) sink response to increasing atmospheric CO2. Free-Air CO2 Enrichment (FACE) experiments lasting a decade or more have investigated ecosystem responses to a step change in atmospheric CO2 concentration. To interpret FACE results in the context of gradual increases in atmospheric CO2 over decades to centuries, we used a suite of seven models to simulate the Duke and Oak Ridge FACE experiments extended for 300 years of CO2 enrichment. We also determine key modeling assumptions that drive divergent projections of terrestrial C uptake and evaluate whether these assumptions can be constrained by experimental evidence. All models simulated increased terrestrial C pools resulting from CO2 enrichment, though there was substantial variability in quasi-equilibrium C sequestration and rates of change. In two of two models that assume that plant nitrogen (N) uptake is solely a function of soil N supply, the net primary production response to elevated CO2 became progressively N limited. In four of five models that assume that N uptake is a function of both soil N supply and plant N demand, elevated CO2 led to reduced ecosystem N losses and thus progressively relaxed nitrogen limitation. Many allocation assumptions resulted in increased wood allocation relative to leaves and roots which reduced the vegetation turnover rate and increased C sequestration. In addition, self-thinning assumptions had a substantial impact on C sequestration in two models. Accurate representation of N process dynamics (in particular N uptake), allocation, and forest self-thinning is key to minimizing uncertainty in projections of future C sequestration in response to elevated atmospheric CO2.
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| 35. |
- Wang, Bo, et al.
(författare)
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Accelerated resolution of AA amyloid in heparanase knockout mice is associated with matrix metalloproteases
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- AA-amyloidosis is a disease characterized by abnormal deposition of serum A amyloid (SAA) peptide along with other components in various organs. The disease is a complication of inflammatory conditions that cause persistent high levels of the acute phase reactant SAA in plasma. In experimental animal models, the deposited amyloid is resolved when the inflammation is stopped, suggesting that there is an efficient clearance mechanism for the amyloid. As heparan sulfate (HS) is one of the major components in the amyloid, its metabolism is expected to affect the pathology of AA amyloidosis. In this study, we investigated the effect of heparanase, a HS degradation enzyme, in resolution of the AA amyloid. The transgenic mice deficient in heparanase (Hpa-KO) produced a similar level of SAA in plasma as the wildtype control (Ctr) mice upon induction by injection of AEF (amyloid enhancing factor) and inflammatory stimuli. The induction resulted in formation of SAA amyloid 7-days post treatment in the spleen that displayed a comparable degree of amyloid load in both groups. The amyloid became significantly less in the Hpa-KO spleen than in the Ctr spleen 10-days post treatment, and was completely resolved in the Hpa-KO spleen on day 21 post induction, while a substantial amount was still detected in the Ctr spleen. The rapid clearance of the amyloid in the Hpa-KO mice can be ascribed to upregulated matrix metalloproteases (MMPs) that are believed to contribute to degradation of the protein components in the AA amyloid. The results indicate that both heparanase and MMPs play important parts in the pathological process of AA amyloidosis.
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| 36. |
- Whitley, Rhys, et al.
(författare)
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A model inter-comparison study to examine limiting factors in modelling Australian tropical savannas
- 2016
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 13:11, s. 3245-3265
-
Tidskriftsartikel (refereegranskat)abstract
- The savanna ecosystem is one of the most dominant and complex terrestrial biomes, deriving from a distinct vegetative surface comprised of co-dominant tree and grass populations. While these two vegetation types co-exist functionally, demographically they are not static but are dynamically changing in response to environmental forces such as annual fire events and rainfall variability. Modelling savanna environments with the current generation of terrestrial biosphere models (TBMs) has presented many problems, particularly describing fire frequency and intensity, phenology, leaf biochemistry of C3 and C4 photosynthesis vegetation, and root-water uptake. In order to better understand why TBMs perform so poorly in savannas, we conducted a model inter-comparison of six TBMs and assessed their performance at simulating latent energy (LE) and gross primary productivity (GPP) for five savanna sites along a rainfall gradient in northern Australia. Performance in predicting LE and GPP was measured using an empirical benchmarking system, which ranks models by their ability to utilise meteorological driving information to predict the fluxes. On average, the TBMs performed as well as a multi-linear regression of the fluxes against solar radiation, temperature and vapour pressure deficit but were outperformed by a more complicated nonlinear response model that also included the leaf area index (LAI). This identified that the TBMs are not fully utilising their input information effectively in determining savanna LE and GPP and highlights that savanna dynamics cannot be calibrated into models and that there are problems in underlying model processes. We identified key weaknesses in a model's ability to simulate savanna fluxes and their seasonal variation, related to the representation of vegetation by the models and root-water uptake. We underline these weaknesses in terms of three critical areas for development. First, prescribed tree-rooting depths must be deep enough, enabling the extraction of deep soil-water stores to maintain photosynthesis and transpiration during the dry season. Second, models must treat grasses as a co-dominant interface for water and carbon exchange rather than a secondary one to trees. Third, models need a dynamic representation of LAI that encompasses the dynamic phenology of savanna vegetation and its response to rainfall interannual variability. We believe that this study is the first to assess how well TBMs simulate savanna ecosystems and that these results will be used to improve the representation of savannas ecosystems in future global climate model studies.
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| 37. |
- Whitley, Rhys, et al.
(författare)
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Challenges and opportunities in land surface modelling of savanna ecosystems
- 2017
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:20, s. 4711-4732
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Tidskriftsartikel (refereegranskat)abstract
- The savanna complex is a highly diverse global biome that occurs within the seasonally dry tropical to sub-tropical equatorial latitudes and are structurally and functionally distinct from grasslands and forests. Savannas are open-canopy environments that encompass a broad demographic continuum, often characterised by a changing dominance between C3-tree and C4-grass vegetation, where frequent environmental disturbances such as fire modulates the balance between ephemeral and perennial life forms. Climate change is projected to result in significant changes to the savanna floristic structure, with increases to woody biomass expected through CO2 fertilisation in mesic savannas and increased tree mortality expected through increased rainfall interannual variability in xeric savannas. The complex interaction between vegetation and climate that occurs in savannas has traditionally challenged terrestrial biosphere models (TBMs), which aim to simulate the interaction between the atmosphere and the land surface to predict responses of vegetation to changing in environmental forcing. In this review, we examine whether TBMs are able to adequately represent savanna fluxes and what implications potential deficiencies may have for climate change projection scenarios that rely on these models. We start by highlighting the defining characteristic traits and behaviours of savannas, how these differ across continents and how this information is (or is not) represented in the structural framework of many TBMs. We highlight three dynamic processes that we believe directly affect the water use and productivity of the savanna system: phenology, root-water access and fire dynamics. Following this, we discuss how these processes are represented in many current-generation TBMs and whether they are suitable for simulating savanna fluxes.Finally, we give an overview of how eddy-covariance observations in combination with other data sources can be used in model benchmarking and intercomparison frameworks to diagnose the performance of TBMs in this environment and formulate road maps for future development. Our investigation reveals that many TBMs systematically misrepresent phenology, the effects of fire and root-water access (if they are considered at all) and that these should be critical areas for future development. Furthermore, such processes must not be static (i.e. prescribed behaviour) but be capable of responding to the changing environmental conditions in order to emulate the dynamic behaviour of savannas. Without such developments, however, TBMs will have limited predictive capability in making the critical projections needed to understand how savannas will respond to future global change.
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| 38. |
- Xu, An, et al.
(författare)
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Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.
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| 39. |
- Xu, Ping, et al.
(författare)
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Gender Differences in the Associations Between Physical Activity, Smartphone Use, and Weight Stigma
- 2022
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPhysical activity (PA) is important for health. However, there is little evidence on how weight stigma, time spent on sedentary activities (including smartphone, social media, online learning), time spent on outdoor activity, and nomophobia associate with PA among Chinese individuals with consideration of gender. The present study examined the aforementioned associations in the COVID-19 pandemic era. MethodsUniversity students (N = 3,135; 1,798 females, 1,337 males) with a mean age of 19.65 years (SD = 2.38) years completed an online survey from November to December, 2021. The online survey assessed weight stigma (using the Perceived Weight Stigma Scale and Weight Bias Internalization Scale), PA (using the International Physical Activity Questionnaire Short Form), time spent on different activities (using self-designed items for time on smartphone, outdoor activity, social media, and online learning), and nomophobia (using the Nomophobia Questionnaire). Parallel mediation models were constructed (dependent variable: PA; mediators: perceived weight stigma, weight-related self-stigma, time spent on smartphone, time spent on outdoor activity, time spent on social media, and time spent online learning; independent variable: nomophobia) and evaluated using Hayes' Process Macro Model 4 (IBM SPSS 20.0). ResultsWeight-related self-stigma (beta = -0.06; p = 0.03), time spent on outdoor activity (beta = 0.21; p < 0.001), time spent on social media (beta = 0.07; p = 0.02), time spent on online learning (beta = 0.06; p = 0.03), and nomophobia (beta = -0.07; p = 0.01) were all significant factors explaining the PA among female participants. Perceived weight stigma (beta = -0.07; p = 0.01), time spent on outdoor activity (beta = 0.27; p < 0.001), and time spent on online learning (beta = 0.10; p = 0.002) were all significant factors explaining PA among male participants. ConclusionChinese healthcare providers should design programs on weight stigma reduction and outdoor activity improvement to enhance PA among university students.
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| 40. |
- Zhang, Ping, et al.
(författare)
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Deficiency of alkaline SMase enhances dextran sulfate sodium-induced colitis in mice with upregulation of autotaxin
- 2018
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 59:10, s. 1841-1850
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline SMase (Alk-SMase) cleaves phosphocholine from SM, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4- to 5-fold enhanced in Alk-SMase KO mice. Here, we further studied the pathogenesis of colitis induced by dextran sulfate sodium (DSS) in WT and KO mice. Compared with WT mice, KO mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury. Higher levels of PAF and lower levels of interleukin (IL)10 were identified in KO mice 2 days after DSS treatment. A greater and progressive increase of lysophosphatidic acid (LPA) was identified. The change was associated with increased autotaxin expression in both small intestine and colon, which was identified by immunohistochemistry study, Western blot, and sandwich ELISA. The upregulation of autotaxin coincided with an early increase of PAF. IL6 and TNFα were increased in both WT and KO mice. At the later stage (day 8), significant decreases in IL6, IL10, and PAF were identified, and the decreases were greater in KO mice. In conclusion, deficiency of Alk-SMase enhances DSS-induced colitis by mechanisms related to increased autotaxin expression and LPA formation. The early increase of PAF might be a trigger for such reactions.
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| 41. |
- Zhang, Tianji, et al.
(författare)
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In-depth characterization of 1,4-butanediol diglycidyl ether substituted hyaluronic acid hydrogels
- 2023
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 307
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Tidskriftsartikel (refereegranskat)abstract
- BDDE substituted HA hydrogels remain the most commonly used HA product in the biomedical field. The physical and biochemical properties of the hydrogels are dependent on the degree of modification and substitution patterns/positions, thus, characterizing their fine structure is of great importance for quality assurance. In this study, we developed novel LC-MS methods for accurate determination of MoD as well as in-depth characterization of the linkage network. Fragments resulted from enzymatic depolymerization were resolved by a porous graphitic carbon column followed by online tandem-MS for determining the modification site/residue. With high-resolution separation, two types of previously unknown structures were detected in the cross-linked fragments of 2-B-2 and 4-B-2. Based on the feature of resistance to NaBH4 reduction, these structures contain a GlcNAc residue modified at OH1. This special sugar unit likely derived from reducing end of the native polysaccharide could be a signature to discriminate subtle batch to batch variations.
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| 42. |
- Zhang, Xiao, et al.
(författare)
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Heparanase overexpression impedes perivascular clearance of amyloid-beta from murine brain : relevance to Alzheimer's disease
- 2021
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Ingår i: Acta neuropathologica communications. - : BioMed Central (BMC). - 2051-5960. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Defective amyloid-beta (A beta) clearance from the brain is a major contributing factor to the pathophysiology of Alzheimer's disease (AD). A beta clearance is mediated by macrophages, enzymatic degradation, perivascular drainage along the vascular basement membrane (VBM) and transcytosis across the blood-brain barrier (BBB). AD pathology is typically associated with cerebral amyloid angiopathy due to perivascular accumulation of A beta. Heparan sulfate (HS) is an important component of the VBM, thought to fulfill multiple roles in AD pathology. We previously showed that macrophage-mediated clearance of intracortically injected A beta was impaired in the brains of transgenic mice overexpressing heparanase (Hpa-tg). This study revealed that perivascular drainage was impeded in the Hpa-tg brain, evidenced by perivascular accumulation of the injected A beta in the thalamus of Hpa-tg mice. Furthermore, endogenous A beta accumulated at the perivasculature of Hpa-tg thalamus, but not in control thalamus. This perivascular clearance defect was confirmed following intracortical injection of dextran that was largely retained in the perivasculature of Hpa-tg brains, compared to control brains. Hpa-tg brains presented with thicker VBMs and swollen perivascular astrocyte endfeet, as well as elevated expression of the BBB-associated water-pump protein aquaporin 4 (AQP4). Elevated levels of both heparanase and AQP4 were also detected in human AD brain. These findings indicate that elevated heparanase levels alter the organization and composition of the BBB, likely through increased fragmentation of BBB-associated HS, resulting in defective perivascular drainage. This defect contributes to perivascular accumulation of A beta in the Hpa-tg brain, highlighting a potential role for heparanase in the pathogenesis of AD.
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| 43. |
- Zhou, Dapeng, et al.
(författare)
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Lysosomal glycosphingolipid recognition by NKT cells.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 306:5702, s. 1786-9
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Tidskriftsartikel (refereegranskat)abstract
- NKT cells represent a distinct lineage of T cells that coexpress a conserved alphabeta T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking beta-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity.
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| 44. |
- Zhu, Wuyang, et al.
(författare)
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Interaction of E2 glycoprotein with heparan sulfate is crucial for cellular infection of Sindbis virus
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9656-
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Tidskriftsartikel (refereegranskat)abstract
- Cell culture-adapted strains of Sindbis virus (SINV) initially attach to cells by the ability to interact with heparan sulfate (HS) through selective mutation for positively charged amino acid (aa) scattered in E2 glycoprotein (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72: 7357-7366, 1998). Here we have further confirmed that interaction of E2 protein with HS is crucial for cellular infection of SINV based on the reverse genetic system of XJ-160 virus, a Sindbis-like virus (SINLV). Both SINV YN87448 and SINLV XJ-160 displayed similar infectivity on BHK-21, Vero, or C6/36 cells, but XJ-160 failed to infect mouse embryonic fibroblast (MEF) cells. The molecular mechanisms underlying the selective infectivity of XJ-160 were approached by substituting the E1, E2, or both genes of XJ-160 with that of YN87448, and the chimeric virus was denominated as XJ-160/E1, XJ-160/E2, or XJ-160/E1E2, respectively. In contrast to the parental XJ-160, all chimeric viruses became infectious to wild-type MEF cells (MEF-wt). While MEF-Ext(-/-) cells, producing shortened HS chains, were resistant not only to XJ-160, but also to YN87448 as well as the chimeric viruses, indicating that the inability of XJ-160 to infect MEF-wt cells likely due to its incompetent discrimination of cellular HS. Treatment with heparin or HS-degrading enzyme resulted in a substantial decrease in plaque formation by YN87448, XJ-160/E2, and XJ-160/E1E2, but had marginal effect on XJ-160 and XJ-160/E1, suggesting that E2 glycoprotein from YN87448 plays a more important role than does E1 in mediating cellular HS-related cell infection. In addition, the peptide containing 145-150 aa from E2 gene of YN87448 specifically bound to heparin, while the corresponding peptide from the E2 gene of XJ-160 essentially showed no binding to heparin. As a new dataset, these results clearly confirm an essential role of E2 glycoprotein, especially the domain of 145-150 aa, in SINV cellular infection through the interaction with HS.
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