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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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| 3. |
- 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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| 5. |
- Vuholm, S., et al.
(författare)
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Whole-grain rye and wheat affect some markers of gut health without altering the fecal microbiota in healthy overweight adults: A 6-week randomized trial
- 2017
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 147:11, s. 2067-2075
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Tidskriftsartikel (refereegranskat)abstract
- Whole grains have shown potential for improving gut health, but evidence comparing different whole-grain types is lacking. Objective:We investigated whether whole-grain wheat (WGW) and whole-grain rye (WGR) improve gut health in different ways compared to refined wheat (RW), with the primary outcomes of microbiota composition and gastrointestinal (GI) symptoms. Methods: In a randomized parallel trial, 70 healthy adults (in means ± SDs; aged 51.0 ± 9.4 y, body mass index [BMI (in kg/m2)] 27.8 ± 1.9, 32:38 men:women) replaced cereal foods from their habitual diet with WGR, WGW, or RW (control). Before and after a 6-wk intervention, a spot stool sample was collected and analyzed for short-chain fatty acids and microbiota composition through the use of 16S ribosomal RNA gene-targeted high-throughput amplicon sequencing. GI symptoms and stool regularity were evaluated by questionnaires at baseline and after weeks 2, 4, and 6. Results: Intakes of whole grains were 145.2 ± 75.9, 124.2 ± 57.3, and 5.4 ± 3.2 g/d in the WGW, WGR, and RW groups, respectively. Gut microbiota composition was not affected by diet. The relative change in fecal butyrate decreased in the RW (238%) group compared to the WGW (25%, P = 0.014) and WGR groups (21%, P = 0.037). Other short-chain fatty acids were unaffected. Flatulence was more frequent following intake of WGW (OR: 2.06, 95% CI: 1.03, 4.17) and WGR (OR: 2.62, 95% CI: 1.35, 5.22) compared to RW, whereas bloating was less frequent following WGW (OR: 0.38, 95% CI: 0.18, 0.80) and WGR (OR: 0.34, 95% CI: 0.16, 0.72). Stool frequency increased following WGR but not WGW, compared to RW in weeks 2 (0.4 defecations/d, P = 0.049) and 4 (0.5 defecations/d, P = 0.043), but not in week 6. The WGW and WGR groups did not differ from each other in any of the variables tested. Conclusion: Regular consumption ofWGR andWGWaffected fecal butyrate concentration and gastrointestinal symptoms in healthy overweight adults, supporting the hypothesis thatWGR andWGWcan be included in the diet equally tomaintain gut health.
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| 6. |
- Chadburn, S. E., et al.
(författare)
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An observation-based constraint on permafrost loss as a function of global warming
- 2017
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Ingår i: Nature Climate Change. - 1758-678X .- 1758-6798. ; 7:5, s. 340-344
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Tidskriftsartikel (refereegranskat)abstract
- Permafrost, which covers 15 million km(2) of the land surface, is one of the components of the Earth system that is most sensitive to warming(1,2). Loss of permafrost would radically change high-latitude hydrology and biogeochemical cycling, and could therefore provide very significant feedbacks on climate change(3-8). The latest climate models all predict warming of high-latitude soils and thus thawing of permafrost under future climate change, but with widely varying magnitudes of permafrost thaw(9,10). Here we show that in each of the models, their present-day spatial distribution of permafrost and air temperature can be used to infer the sensitivity of permafrost to future global warming. Using the same approach for the observed permafrost distribution and air temperature, we estimate a sensitivity of permafrost area loss to global mean warming at stabilization of 4.0(-1.1)(+1.0) million km(2) degrees C-1 (1 sigma confidence), which is around 20% higher than previous studies(9). Our method facilitates an assessment for COP21 climate change targets(11): if the climate is stabilized at 2 degrees C above pre-industrial levels, we estimate that the permafrost area would eventually be reduced by over 40%. Stabilizing at 1.5 degrees C rather than 2 degrees C would save approximately 2 million km(2) of permafrost.
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| 7. |
- Chadburn, Sarah E., et al.
(författare)
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Carbon stocks and fluxes in the high latitudes : using site-level data to evaluate Earth system models
- 2017
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:22, s. 5143-5169
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Tidskriftsartikel (refereegranskat)abstract
- It is important that climate models can accurately simulate the terrestrial carbon cycle in the Arctic due to the large and potentially labile carbon stocks found in permafrost-affected environments, which can lead to a positive climate feedback, along with the possibility of future carbon sinks from northward expansion of vegetation under climate warming. Here we evaluate the simulation of tundra carbon stocks and fluxes in three land surface schemes that each form part of major Earth system models (JSBACH, Germany; JULES, UK; ORCHIDEE, France). We use a site-level approach in which comprehensive, high-frequency datasets allow us to disentangle the importance of different processes. The models have improved physical permafrost processes and there is a reasonable correspondence between the simulated and measured physical variables, including soil temperature, soil moisture and snow. We show that if the models simulate the correct leaf area index (LAI), the standard C3 photosynthesis schemes produce the correct order of magnitude of carbon fluxes. Therefore, simulating the correct LAI is one of the first priorities. LAI depends quite strongly on climatic variables alone, as we see by the fact that the dynamic vegetation model can simulate most of the differences in LAI between sites, based almost entirely on climate inputs. However, we also identify an influence from nutrient limitation as the LAI becomes too large at some of the more nutrient-limited sites. We conclude that including moss as well as vascular plants is of primary importance to the carbon budget, as moss contributes a large fraction to the seasonal CO2 flux in nutrient-limited conditions. Moss photosynthetic activity can be strongly influenced by the moisture content of moss, and the carbon uptake can be significantly different from vascular plants with a similar LAI. The soil carbon stocks depend strongly on the rate of input of carbon from the vegetation to the soil, and our analysis suggests that an improved simulation of photosynthesis would also lead to an improved simulation of soil carbon stocks. However, the stocks are also influenced by soil carbon burial (e.g. through cryoturbation) and the rate of heterotrophic respiration, which depends on the soil physical state. More detailed below-ground measurements are needed to fully evaluate biological and physical soil processes. Furthermore, even if these processes are well modelled, the soil carbon profiles cannot resemble peat layers as peat accumulation processes are not represented in the models. Thus, we identify three priority areas for model development: (1) dynamic vegetation including (a) climate and (b) nutrient limitation effects; (2) adding moss as a plant functional type; and an (3) improved vertical profile of soil carbon including peat processes.
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| 8. |
- Claeys, Shana, et al.
(författare)
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ALK positively regulates MYCN activity through repression of HBP1 expression
- 2019
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 38:15, s. 2690-2705
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Tidskriftsartikel (refereegranskat)abstract
- ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis. To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential. We show that mutant ALK downregulates the ‘HMG-box transcription factor 1’ (HBP1) through the PI3K-AKT–FOXO3a signaling axis. HBP1 inhibits both the transcriptional activating and repressing activity of MYCN, the latter being mediated through PRC2 activity. HBP1 itself is under negative control of MYCN through miR-17~92. Combined targeting of HBP1 by PI3K antagonists and MYCN signaling by BET- or HDAC-inhibitors blocks MYCN activity and significantly reduces tumor growth, suggesting a novel targeted therapy option for high-risk neuroblastoma.
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| 9. |
- Mueller, Anna A., et al.
(författare)
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An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection
- 2016
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella Typhimurium (S. Tm) is a common cause of self-limiting diarrhea. The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses, particularly the mucosal NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches the gut from homeostasis to inflammation. This was studied using the streptomycin mouse model. S. Tm infections in knockout mice, cytokine inhibition and -injection experiments revealed that caspase-1 (not -11) dependent IL-18 is pivotal for inducing acute inflammation. IL-18 boosted NK cell chemoattractants and enhanced the NK cells' migratory capacity, thus promoting mucosal accumulation of mature, activated NK cells. NK cell depletion and Prf(-/-) ablation (but not granulocyte-depletion or T-cell deficiency) delayed tissue inflammation. Our data suggest an NK cell perforin response as one limiting factor in mounting gut mucosal inflammation. Thus, IL-18-elicited NK cell perforin responses seem to be critical for coordinating mucosal inflammation during early infection, when S. Tm strongly relies on virulence factors detectable by the inflammasome. This may have broad relevance for mucosal defense against microbial pathogens.
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| 11. |
- Westermann, Alexander J., et al.
(författare)
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The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in Salmonella enterica Serovar Typhimurium
- 2019
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs.IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria.
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