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| 2. |
- Carmona-Gutierrez, D., et al.
(författare)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Forskningsöversikt (refereegranskat)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 5. |
- Renette, Cas, et al.
(författare)
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Simulating the effect of subsurface drainage on the thermal regime and ground ice in blocky terrain in Norway
- 2023
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Ingår i: Earth Surface Dynamics. - : Copernicus GmbH. - 2196-6311 .- 2196-632X. ; 11:1, s. 33-50
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Tidskriftsartikel (refereegranskat)abstract
- Ground temperatures in coarse, blocky deposits such as mountain blockfields and rock glaciers have long been observed to be lower in comparison with other (sub)surface material. One of the reasons for this negative temperature anomaly is the lower soil moisture content in blocky terrain, which decreases the duration of the zero curtain in autumn. Here we used the CryoGrid community model to simulate the effect of drainage on the ground thermal regime and ground ice in blocky terrain permafrost at two sites in Norway. The model set-up is based on a one-dimensional model domain and features a surface energy balance, heat conduction and advection, as well as a bucket water scheme with adjustable lateral drainage. We used three idealized subsurface stratigraphies, blocks only, blocks with sediment and sediment only, which can be either drained (i.e. with strong lateral subsurface drainage) or undrained (i.e. without drainage), resulting in six scenarios. The main difference between the three stratigraphies is their ability to retain water against drainage: while the blocks only stratigraphy can only hold small amounts of water, much more water is retained within the sediment phase of the two other stratigraphies, which critically modifies the freeze-thaw behaviour. The simulation results show markedly lower ground temperatures in the blocks only, drained scenario compared to other scenarios, with a negative thermal anomaly of up to 2.2 degrees C. For this scenario, the model can in particular simulate the time evolution of ground ice, with build-up during and after snowmelt and spring and gradual lowering of the ice table in the course of the summer season. The thermal anomaly increases with larger amounts of snowfall, showing that well-drained blocky deposits are less sensitive to insulation by snow than other soils. We simulate stable permafrost conditions at the location of a rock glacier in northern Norway with a mean annual ground surface temperature of 2.0-2.5 degrees C in the blocks only, drained simulations. Finally, transient simulations since 1951 at the rock glacier site (starting with permafrost conditions for all stratigraphies) showed a complete loss of perennial ground ice in the upper 5 m of the ground in the blocks with sediment, drained run; a 1.6 m lowering of the ground ice table in the sediment only, drained run; and only 0.1 m lowering in the blocks only, drained run. The interplay between the subsurface water-ice balance and ground freezing/thawing driven by heat conduction can at least partly explain the occurrence of permafrost in coarse blocky terrain below the elevational limit of permafrost in non-blocky sediments. It is thus important to consider the subsurface water-ice balance in blocky terrain in future efforts in permafrost distribution mapping in mountainous areas. Furthermore, an accurate prediction of the evolution of the ground ice table in a future climate can have implications for slope stability, as well as water resources in arid environments.
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| 7. |
- Aprile, E., et al.
(författare)
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Material radiopurity control in the XENONnT experiment
- 2022
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:7
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Tidskriftsartikel (refereegranskat)abstract
- The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and 222Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background (∼∼17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected 222Rn activity concentration in XENONnT is determined to be 4.2 (+0.5−0.7) μBq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.
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| 10. |
- Fliegauf, M, et al.
(författare)
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Detrimental NFKB1 missense variants affecting the Rel-homology domain of p105/p50
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 965326-
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Tidskriftsartikel (refereegranskat)abstract
- Most of the currently known heterozygous pathogenic NFKB1 (Nuclear factor kappa B subunit 1) variants comprise deleterious defects such as severe truncations, internal deletions, and frameshift variants. Collectively, these represent the most frequent monogenic cause of common variable immunodeficiency (CVID) identified so far. NFKB1 encodes the transcription factor precursor p105 which undergoes limited proteasomal processing of its C-terminal half to generate the mature NF-κB subunit p50. Whereas p105/p50 haploinsufficiency due to devastating genetic damages and protein loss is a well-known disease mechanism, the pathogenic significance of numerous NFKB1 missense variants still remains uncertain and/or unexplored, due to the unavailability of accurate test procedures to confirm causality. In this study we functionally characterized 47 distinct missense variants residing within the N-terminal domains, thus affecting both proteins, the p105 precursor and the processed p50. Following transient overexpression of EGFP-fused mutant p105 and p50 in HEK293T cells, we used fluorescence microscopy, Western blotting, electrophoretic mobility shift assays (EMSA), and reporter assays to analyze their effects on subcellular localization, protein stability and precursor processing, DNA binding, and on the RelA-dependent target promoter activation, respectively. We found nine missense variants to cause harmful damage with intensified protein decay, while two variants left protein stability unaffected but caused a loss of the DNA-binding activity. Seven of the analyzed single amino acid changes caused ambiguous protein defects and four variants were associated with only minor adverse effects. For 25 variants, test results were indistinguishable from those of the wildtype controls, hence, their pathogenic impact remained elusive. In summary, we show that pathogenic missense variants affecting the Rel-homology domain may cause protein-decaying defects, thus resembling the disease-mechanisms of p105/p50 haploinsufficiency or may cause DNA-binding deficiency. However, rare variants (with a population frequency of less than 0.01%) with minor abnormalities or with neutral tests should still be considered as potentially pathogenic, until suitable tests have approved them being benign.
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| 11. |
- Haller, Paul M., et al.
(författare)
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Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus
- 2023
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Ingår i: European Journal of Preventive Cardiology. - 2047-4873 .- 2047-4881. ; 30:12, s. 1218-1226
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. 'METHODS AND RESULTS: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81).CONCLUSION: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.
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| 12. |
- Hinrichsen, F., et al.
(författare)
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Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 33:12
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Tidskriftsartikel (refereegranskat)abstract
- Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2(Delta IEC)). Hk2(Delta IEC) mice were less susceptible to acute colitis. Analyzing the epithelial transcriptome from Hk2(Delta IEC) mice during colitis and using HK2-deficient intestinal organoids and Caco-2 cells revealed reduced mitochondrial respiration and epithelial cell death in the absence of HK2. The microbiota strongly regulated HK2 expression and activity. The microbially derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression via histone deacetylase 8 (HDAC8) and reduced mitochondrial respiration in wild-type but not in HK2-deficient Caco-2 cells. Butyrate supplementation protected wild-type but not Hk2(Delta IEC) mice from colitis. Our findings define a mechanism how butyrate promotes intestinal homeostasis and suggest targeted HK2-inhibition as therapeutic avenue for inflammation.
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| 13. |
- Neumann, J. T., et al.
(författare)
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Application of High-Sensitivity Troponin in Suspected Myocardial Infarction
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:26, s. 2529-2540
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundData regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. MethodsIn 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. ResultsAmong 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. ConclusionsA risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes.
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| 14. |
- Palmtag, Juri, 1980-, et al.
(författare)
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A high spatial resolution soil carbon and nitrogen dataset for the northern permafrost region based on circumpolar land cover upscaling
- 2022
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Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 14:9, s. 4095-4110
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Tidskriftsartikel (refereegranskat)abstract
- Soils in the northern high latitudes are a key component in the global carbon cycle; the northern permafrost region covers 22% of the Northern Hemisphere land surface area and holds almost twice as much carbon as the atmosphere. Permafrost soil organic matter stocks represent an enormous long-term carbon sink which is in risk of switching to a net source in the future. Detailed knowledge about the quantity and the mechanisms controlling organic carbon storage is of utmost importance for our understanding of potential impacts of and feedbacks on climate change. Here we present a geospatial dataset of physical and chemical soil properties calculated from 651 soil pedons encompassing more than 6500 samples from 16 different study areas across the northern permafrost region. The aim of our dataset is to provide a basis to describe spatial patterns in soil properties, including quantifying carbon and nitrogen stocks. There is a particular need for spatially distributed datasets of soil properties, including vertical and horizontal distribution patterns, for modeling at local, regional, or global scales. This paper presents this dataset, describes in detail soil sampling; laboratory analysis, and derived soil geochemical parameters; calculations; and data clustering. Moreover, we use this dataset to estimate soil organic carbon and total nitrogen storage estimates in soils in the northern circumpolar permafrost region (17.9 x 106 km2) using the European Space Agency's (ESA's) Climate Change Initiative (CCI) global land cover dataset at 300m pixel resolution. We estimate organic carbon and total nitrogen stocks on a circumpolar scale (excluding Tibet) for the 0-100 and 0-300 cm soil depth to be 380 and 813 Pg for carbon, and 21 and 55 Pg for nitrogen, respectively. Our organic carbon estimates agree with previous studies, with most recent estimates of 1000 Pg (170 to C186 Pg) to 300 cm depth. Two separate datasets are freely available on the Bolin Centre Database repository (https://doi.org/10.17043/palmtag-2022-pedon-1, Palmtag et al., 2022a; and https://doi.org/10.17043/palmtag-2022-spatial-1, Palmtag et al., 2002b).
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| 15. |
- Peterziel, H, et al.
(författare)
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Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
- 2022
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 6:1, s. 94-
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Tidskriftsartikel (refereegranskat)abstract
- The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.
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| 19. |
- Treat, Claire C., et al.
(författare)
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Permafrost Carbon : Progress on Understanding Stocks and Fluxes Across Northern Terrestrial Ecosystems
- 2024
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Ingår i: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 129:3
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Tidskriftsartikel (refereegranskat)abstract
- Significant progress in permafrost carbon science made over the past decades include the identification of vast permafrost carbon stocks, the development of new pan-Arctic permafrost maps, an increase in terrestrial measurement sites for CO2 and methane fluxes, and important factors affecting carbon cycling, including vegetation changes, periods of soil freezing and thawing, wildfire, and other disturbance events. Process-based modeling studies now include key elements of permafrost carbon cycling and advances in statistical modeling and inverse modeling enhance understanding of permafrost region C budgets. By combining existing data syntheses and model outputs, the permafrost region is likely a wetland methane source and small terrestrial ecosystem CO2 sink with lower net CO2 uptake toward higher latitudes, excluding wildfire emissions. For 2002–2014, the strongest CO2 sink was located in western Canada (median: −52 g C m−2 y−1) and smallest sinks in Alaska, Canadian tundra, and Siberian tundra (medians: −5 to −9 g C m−2 y−1). Eurasian regions had the largest median wetland methane fluxes (16–18 g CH4 m−2 y−1). Quantifying the regional scale carbon balance remains challenging because of high spatial and temporal variability and relatively low density of observations. More accurate permafrost region carbon fluxes require: (a) the development of better maps characterizing wetlands and dynamics of vegetation and disturbances, including abrupt permafrost thaw; (b) the establishment of new year-round CO2 and methane flux sites in underrepresented areas; and (c) improved models that better represent important permafrost carbon cycle dynamics, including non-growing season emissions and disturbance effects.
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| 20. |
- Westermann, D., et al.
(författare)
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Voltage source converter (VSC) HVDC for bulk power transmission - Technology and planning method
- 2010
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Ingår i: 2010. ACDC. 9th IET International Conference on AC and DC Power Transmission. - : IET. - 9781849193085
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Konferensbidrag (refereegranskat)abstract
- As the value of additional functionality of any new power technology is very case dependent, it is not possible to make general comments on the economics of VSC HVDC applications for bulk power transmission without considering alternatives. Therefore, the paper presents a methodology which can be used to evaluate different investment options, based on the investment cost, the operational costs and a way to include the "non-component based" costs and returns.
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| 21. |
- Westermann, Sebastian, et al.
(författare)
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The CryoGrid community model (version 1.0) - a multi-physics toolbox for climate-driven simulations in the terrestrial cryosphere
- 2023
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Ingår i: Geoscientific Model Development. - 1991-959X .- 1991-9603. ; 16, s. 2607-2647
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Tidskriftsartikel (refereegranskat)abstract
- The CryoGrid community model is a flexible toolbox for simulating the ground thermal regime and the ice-water balance for permafrost and glaciers, extending a well-established suite of permafrost models (CryoGrid 1, 2, and 3). The CryoGrid community model can accommodate a wide variety of application scenarios, which is achieved by fully modular structures through object-oriented programming. Different model components, characterized by their process representations and parameterizations, are realized as classes (i.e., objects) in CryoGrid. Standardized communication protocols between these classes ensure that they can be stacked vertically. For example, the CryoGrid community model features several classes with different complexity for the seasonal snow cover, which can be flexibly combined with a range of classes representing subsurface materials, each with their own set of process representations (e.g., soil with and without water balance, glacier ice). We present the CryoGrid architecture as well as the model physics and defining equations for the different model classes, focusing on one-dimensional model configurations which can also interact with external heat and water reservoirs. We illustrate the wide variety of simulation capabilities for a site on Svalbard, with point-scale permafrost simulations using, e.g., different soil freezing characteristics, drainage regimes, and snow representations, as well as simulations for glacier mass balance and a shallow water body. The CryoGrid community model is not intended as a static model framework but aims to provide developers with a flexible platform for efficient model development. In this study, we document both basic and advanced model functionalities to provide a baseline for the future development of novel cryosphere models.
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