| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Peters, W., et al.
(författare)
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Seven years of recent European net terrestrial carbon dioxide exchange constrained by atmospheric observations
- 2010
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 16:4, s. 1317-1337
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Tidskriftsartikel (refereegranskat)abstract
- We present an estimate of net ecosystem exchange (NEE) of CO2 in Europe for the years 2001-2007. It is derived with a data assimilation that uses a large set of atmospheric CO2 mole fraction observations (similar to 70 000) to guide relatively simple descriptions of terrestrial and oceanic net exchange, while fossil fuel and fire emissions are prescribed. Weekly terrestrial sources and sinks are optimized (i.e., a flux inversion) for a set of 18 large ecosystems across Europe in which prescribed climate, weather, and surface characteristics introduce finer scale gradients. We find that the terrestrial biosphere in Europe absorbed a net average of -165 Tg C yr-1 over the period considered. This uptake is predominantly in non-EU countries, and is found in the northern coniferous (-94 Tg C yr-1) and mixed forests (-30 Tg C yr-1) as well as the forest/field complexes of eastern Europe (-85 Tg C yr-1). An optimistic uncertainty estimate derived using three biosphere models suggests the uptake to be in a range of -122 to -258 Tg C yr-1, while a more conservative estimate derived from the a-posteriori covariance estimates is -165 +/- 437 Tg C yr-1. Note, however, that uncertainties are hard to estimate given the nature of the system and are likely to be significantly larger than this. Interannual variability in NEE includes a reduction in uptake due to the 2003 drought followed by 3 years of more than average uptake. The largest anomaly of NEE occurred in 2005 concurrent with increased seasonal cycles of observed CO2. We speculate these changes to result from the strong negative phase of the North Atlantic Oscillation in 2005 that lead to favorable summer growth conditions, and altered horizontal and vertical mixing in the atmosphere. All our results are available through http://www.carbontracker.eu.
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| 4. |
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| 5. |
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| 6. |
- Gladyshev, VN, et al.
(författare)
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Selenoprotein Gene Nomenclature
- 2016
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 291:46, s. 24036-24040
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Vautard, R., et al.
(författare)
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Skill and uncertainty of a regional air quality model ensemble
- 2009
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 43:31, s. 4822-4832
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Tidskriftsartikel (refereegranskat)abstract
- Recently several regional air quality projects were carried out to support the negotiation under the Clean Air For Europe (CAFE) programme by predicting the impact of emission control policies with an ensemble of models. Within these projects, CITYDELTA and EURODELTA, the fate of air quality at the scale of European cities or that of the European continent was studied using several models. In this article we focus on the results of EURODELTA. The predictive skill of the ensemble of models is described for ozone, nitrogen dioxide and secondary inorganic compounds, and the uncertainty in air quality modelling is examined through the model ensemble spread of concentrations. For ozone daily maxima the ensemble spread origin differs from one region to another. In the neighbourhood of cities or in mountainous areas the spread of predicted values does not span the range of observed data, due to poorly resolved emissions or complex-terrain meteorology. By contrast in Atlantic and North Sea coastal areas the spread of predicted values is found to be larger than the observations. This is attributed to large differences in the boundary conditions used in the different models. For NO2 daily averages the ensemble spread is generally too small compared with observations. This is because models miss highest values occurring in stagnant meteorology in stable boundary layers near cities. For secondary particulate matter compounds the simulated concentration spread is more balanced, observations falling nearly equiprobably within the ensemble, and the spread originates both from meteorology and aerosol chemistry and thermodynamics. © 2008.
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| 8. |
- Cassetta, L, et al.
(författare)
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Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells.MethodsWe developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders.ResultsWe observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC.ConclusionsThis study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.
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| 9. |
- Groeneveld, Tom, et al.
(författare)
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Interactions of the extracellular matrix proteoglycans decorin and biglycan with C1q and collectins
- 2005
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Ingår i: Journal of Immunology. - 1550-6606. ; 175:7, s. 4715-4723
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Tidskriftsartikel (refereegranskat)abstract
- Decorin and biglycan are closely related abundant extracellular matrix proteoglycans that have been shown to bind to C1q. Given the overall structural similarities between C1q and mannose-binding lectin (MBL), the two key recognition molecules of the classical and the lectin complement pathways, respectively, we have examined functional consequences of the interaction of C1q and MBL with decorin and biglycan. Recombinant forms of human decorin and biglycan bound C1q via both collagen and globular domains and inhibited the classical pathway. Decorin also bound C1 without activating complement. Furthermore, decorin and biglycan bound efficiently to MBL, but only biglycan could inhibit activation of the lectin pathway. Other members of the collectin family, including human surfactant protein D, bovine collectin-43, and conglutinin also showed binding to decorin and biglycan. Decorin and biglycan strongly inhibited C1q binding to human endothelial cells and U937 cells, and biglycan suppressed C1q-induced MCP-1 and IL-8 production by human endothelial cells. In conclusion, decorin and biglycan act as inhibitors of activation of the complement cascade, cellular interactions, and proinflammatory cytokine production mediated by C1q. These two proteoglycans are likely to down-regulate proinflammatory effects mediated by C1q, and possibly also the collectins, at the tissue level.
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| 10. |
- Koller, Thaddaeus J., et al.
(författare)
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Simple Molecules under High-Pressure and High-Temperature Conditions: Synthesis and Characterization of α- and β-C(NH)2 with Fully sp3-Hybridized Carbon
- 2024
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773.
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Tidskriftsartikel (refereegranskat)abstract
- The elements hydrogen, carbon, and nitrogen are among the most abundant in the solar system. Still, little is known about the ternary compounds these elements can form under the high-pressure and high-temperature conditions found in the outer planets' interiors. These materials are also of significant research interest since they are predicted to feature many desirable properties such as high thermal conductivity and hardness due to strong covalent bonding networks. In this study, the high-pressure high-temperature reaction behavior of malononitrile H2C(CN)(2), dicyandiamide (H2N)(2)C=NCN, and melamine (C3N3)(NH2)(3) was investigated in laser-heated diamond anvil cells. Two previously unknown compounds, namely alpha-C(NH)(2) and beta-C(NH)(2), have been synthesized and found to have fully sp(3)-hybridized carbon atoms. alpha-C(NH)(2) crystallizes in a distorted beta-cristobalite structure, while beta-C(NH)(2) is built from previously unknown imide-bridged 2,4,6,8,9,10-hexaazaadamantane units, which form two independent interpenetrating diamond-like networks. Their stability domains and compressibility were studied, for which supporting density functional theory calculations were performed.
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| 11. |
- Pandey, Sudhanshu, et al.
(författare)
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Enhanced methane emissions from tropical wetlands during the 2011 la Niña
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Year-to-year variations in the atmospheric methane (CH4) growth rate show significant correlation with climatic drivers. The second half of 2010 and the first half of 2011 experienced the strongest La Niña since the early 1980s, when global surface networks started monitoring atmospheric CH4 mole fractions. We use these surface measurements, retrievals of column-averaged CH4 mole fractions from GOSAT, new wetland inundation estimates, and atmospheric δ13C-CH4 measurements to estimate the impact of this strong La Niña on the global atmospheric CH4 budget. By performing atmospheric inversions, we find evidence of an increase in tropical CH4 emissions of ∼6-9 TgCH4 yr-1 during this event. Stable isotope data suggest that biogenic sources are the cause of this emission increase. We find a simultaneous expansion of wetland area, driven by the excess precipitation over the Tropical continents during the La Niña. Two process-based wetland models predict increases in wetland area consistent with observationally-constrained values, but substantially smaller per-area CH4 emissions, highlighting the need for improvements in such models. Overall, tropical wetland emissions during the strong La Niña were at least by 5% larger than the long-term mean.
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| 12. |
- Sałacińska, Anna, et al.
(författare)
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Gneiss-forming events in the Saglek Block, Labrador; a reappraisal of the Uivak gneiss
- 2019
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Ingår i: International journal of earth sciences. - : Springer Science and Business Media LLC. - 1437-3254 .- 1437-3262. ; 108:3, s. 753-778
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Tidskriftsartikel (refereegranskat)abstract
- The Archean gneiss complex of the Saglek Block of Labrador is a part of the North Atlantic Craton, and is correlated with southern West Greenland, both being metamorphosed during a ca. 2.7 Ga event. The main component of the complex is the Eoarchean Uivak orthogneiss, which includes lenses of the Nulliak supracrustal assemblage. Both lithologies are cut by the mafic Saglek metadykes. The Uivak gneisses have been divided into Uivak I grey gneiss and Uivak II augen gneiss. The former underwent ca. 3.6 Ga high-T metamorphism prior to the intrusion of the latter. However, the exact age, nature, and extent of Uivak II gneiss are poorly understood. We present geochemical and geochronological results for both these orthogneisses to help refine the various hypotheses that have been proposed concerning the nature of their protoliths. Magmatic ages of 3746 ± 5 and 3717 ± 6 Ma are consistent with previous estimates for the age of Uivak I gneiss. Uivak II augen gneiss from Maidmonts Island, where there is a clear intrusive relationship between the Uivak II and Uivak I gneissic protoliths, has an age of 3325 ± 3 Ma. This is similar to an homogeneous grey gneiss from St. John’s Harbour, with an age of 3318 ± 5 Ma. Grey gneiss from Big Island is distinctively younger (3219 ± 7 Ma), and equivalent to the ca. 3.24 Ga Lister gneiss. Our study shows that granitic gneisses classified as Uivak II were emplaced 200–300 million years after ca. 3.6 Ga metamorphism and deformation of the Uivak I gneiss. The igneous protolith of Uivak II gneiss pre-dates the Lister gneiss by about 100 Ma. The Uivak I and Lister gneisses are geochemically similar, and are both Tonalite–Trondhjemite–Granodiorite (TTG) gneisses, whereas the Uivak II gneiss is a granitoid partially derived from pre-existing crust. We propose abandoning the term ‘Uivak II gneiss’, and renaming ca. 3.3 Ga granitoids, after the type locality, as Maidmonts gneiss. This restricts the term ‘Uivak gneiss’ to Eoarchean TTG gneisses and removes the necessity for subdividing them into Uivak I and II.
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| 13. |
- Segev, Gideon, et al.
(författare)
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The 2022 solar fuels roadmap
- 2022
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 55:32
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Tidskriftsartikel (refereegranskat)abstract
- Renewable fuel generation is essential for a low carbon footprint economy. Thus, over the last five decades, a significant effort has been dedicated towards increasing the performance of solar fuels generating devices. Specifically, the solar to hydrogen efficiency of photoelectrochemical cells has progressed steadily towards its fundamental limit, and the faradaic efficiency towards valuable products in CO2 reduction systems has increased dramatically. However, there are still numerous scientific and engineering challenges that must be overcame in order to turn solar fuels into a viable technology. At the electrode and device level, the conversion efficiency, stability and products selectivity must be increased significantly. Meanwhile, these performance metrics must be maintained when scaling up devices and systems while maintaining an acceptable cost and carbon footprint. This roadmap surveys different aspects of this endeavor: system benchmarking, device scaling, various approaches for photoelectrodes design, materials discovery, and catalysis. Each of the sections in the roadmap focuses on a single topic, discussing the state of the art, the key challenges and advancements required to meet them. The roadmap can be used as a guide for researchers and funding agencies highlighting the most pressing needs of the field.
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| 14. |
- Tsuruta, Aki, et al.
(författare)
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Methane budget estimates in Finland from the CarbonTracker Europe-CH4 data assimilation system
- 2019
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Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 1600-0889 .- 0280-6509. ; 71:1
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Tidskriftsartikel (refereegranskat)abstract
- We estimated the CH4 budget in Finland for 2004–2014 using the CTE-CH4 data assimilation system with an extended atmospheric CH4 observation network of seven sites from Finland to surrounding regions (Hyytiälä, Kjølnes, Kumpula, Pallas, Puijo, Sodankylä, and Utö). The estimated average annual total emission for Finland is 0.6 ± 0.5 Tg CH4 yr−1. Sensitivity experiments show that the posterior biospheric emission estimates for Finland are between 0.3 and 0.9 Tg CH4 yr−1, which lies between the LPX-Bern-DYPTOP (0.2 Tg CH4 yr−1) and LPJG-WHyMe (2.2 Tg CH4 yr−1) process-based model estimates. For anthropogenic emissions, we found that the EDGAR v4.2 FT2010 inventory (0.4 Tg CH4 yr−1) is likely to overestimate emissions in southernmost Finland, but the extent of overestimation and possible relocation of emissions are difficult to derive from the current observation network. The posterior emission estimates were especially reliant on prior information in central Finland. However, based on analysis of posterior atmospheric CH4, we found that the anthropogenic emission distribution based on a national inventory is more reliable than the one based on EDGAR v4.2 FT2010. The contribution of total emissions in Finland to global total emissions is only about 0.13%, and the derived total emissions in Finland showed no trend during 2004–2014. The model using optimized emissions was able to reproduce observed atmospheric CH4 at the sites in Finland and surrounding regions fairly well (correlation > 0.75, bias < ± ppb), supporting adequacy of the observations to be used in atmospheric inversion studies. In addition to global budget estimates, we found that CTE-CH4 is also applicable for regional budget estimates, where small scale (1x1 in this case) optimization is possible with a dense observation network.
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| 15. |
- Walkowiak, J., et al.
(författare)
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First numerical analysis of runaway electron generation in tungsten-rich plasmas towards ITER
- 2024
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 64:3
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Tidskriftsartikel (refereegranskat)abstract
- The disruption and runaway electron analysis model code was extended to include tungsten impurities in disruption simulations with the aim of studying the runaway electron (RE) generation. This study investigates RE current sensitivity on the following plasma parameters and modelling choices: tungsten concentration, magnetic perturbation strength, electron modelling, thermal quench time and tokamak geometry-ITER-like or ASDEX-like. Our investigation shows that a tungsten concentration below 10-3 does not cause significant RE generation on its own. However, at higher concentrations it is possible to reach a very high RE current. Out of the two tested models of electrons in plasma: fluid and isotropic (kinetic), results from the fluid model are more conservative, which is useful when it comes to safety analysis. However, these results are overly pessimistic when compared to the isotropic model, which is based on a more reliable approach. Our results also show that the hot-tail RE generation mechanism is dominant as a primary source of RE in tungsten induced disruptions, usually providing orders of magnitude higher RE seed than Dreicer generation. We discuss best practices for simulations with tungsten-rich plasma, present the dependence of the safety limits on modelling choices and highlight the biggest shortcoming of the current simulation techniques. The obtained results pave the way for a wider analysis of tungsten impact on the disruption dynamics, including the mitigation techniques for ITER in the case of strong contamination of the plasma with tungsten.
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| 16. |
- Gallego-Villarejo, Lucía, et al.
(författare)
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Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
- 2022
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Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier BV. - 2001-0370. ; 20, s. 5672-5679
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer’s disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with Aβ40 the most abundant species of Aβ. Biophysical measurements indicate that Aβ40 interacts with Big Dynorphin (BigDyn), lowering the amount of hydrophobic aggregates, and slowing down the aggregation kinetics. As expected, we found that BigDyn protects against Aβ40 aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ40 provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.
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| 17. |
- Hofer, M., et al.
(författare)
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International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients
- 2014
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 53:6, s. 1125-1129
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. Methods. We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. Results. Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. Conclusion. We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.
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| 18. |
- Jongedijk, Esmer, et al.
(författare)
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Novel routes towards bioplastics from plants : elucidation of the methylperillate biosynthesis pathway from Salvia dorisiana trichomes
- 2020
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Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 71:10, s. 3052-3065
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Tidskriftsartikel (refereegranskat)abstract
- Plants produce a large variety of highly functionalized terpenoids. Functional groups such as partially unsaturated rings and carboxyl groups provide handles to use these compounds as feedstock for biobased commodity chemicals. For instance, methylperillate, a monoterpenoid found in Salvia dorisiana, may be used for this purpose, as it carries both an unsaturated ring and a methylated carboxyl group. The biosynthetic pathway of methylperillate in plants is still unclear. In this work, we identified glandular trichomes from S. dorisiana as the location of biosynthesis and storage of methylperillate. mRNA from purified trichomes was used to identify four genes that can encode the pathway from geranyl diphosphate towards methylperillate. This pathway includes a (-)-limonene synthase (SdLS), a limonene 7-hydroxylase (SdL7H, CYP71A76), and a perillyl alcohol dehydrogenase (SdPOHDH). We also identified a terpene acid methyltransferase, perillic acid O-methyltransferase (SdPAOMT), with homology to salicylic acid OMTs. Transient expression in Nicotiana benthamiana of these four genes, in combination with a geranyl diphosphate synthase to boost precursor formation, resulted in production of methylperillate. This demonstrates the potential of these enzymes for metabolic engineering of a feedstock for biobased commodity chemicals.
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| 19. |
- Moe, Agnes, et al.
(författare)
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The respiratory supercomplex from C. glutamicum
- 2022
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 30:3, s. 338-349
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Tidskriftsartikel (refereegranskat)abstract
- Corynebacterium glutamicum is a preferentially aerobic gram-positive bacterium belonging to the phylum Actinobacteria, which also includes the pathogen Mycobacterium tuberculosis. In these bacteria, respiratory complexes III and IV form a CIII2CIV2 supercomplex that catalyzes oxidation of menaquinol and reduction of dioxygen to water. We isolated the C. glutamicum supercomplex and used cryo-EM to determine its structure at 2.9 Å resolution. The structure shows a central CIII2 dimer flanked by a CIV on two sides. A menaquinone is bound in each of the QN and QP sites in each CIII and an additional menaquinone is positioned ∼14 Å from heme bL. A di-heme cyt. cc subunit electronically connects each CIII with an adjacent CIV, with the Rieske iron-sulfur protein positioned with the iron near heme bL. Multiple subunits interact to form a convoluted sub-structure at the cytoplasmic side of the supercomplex, which defines a path for proton transfer into CIV.
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| 20. |
- Pietrzak, Witold, et al.
(författare)
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Ethanol, feed components and fungal biomass production from field bean (Vicia faba var. equina) seeds in an integrated process
- 2016
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Ingår i: Bioresource Technology. - 0960-8524 .- 1873-2976. ; 216, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- The use of field beans, a non-food leguminous crop, was studied for ethanol, feed components and fungal biomass production. The seeds were hydrolyzed using enzymes or with combination of acid (H3PO4) and alkaline (Ca(OH)2) pretreatment and enzymatic hydrolysis. Fermentation by Saccharomyces cerevisiae, with or without removal of suspended solids, yielded 38.3-42.5gL(-1) ethanol (71.3-79.2% efficiency). The filtration residues contained ca. 247-326gkg(-1) crude protein, 10.6-15.5% acid detergent fiber and 19.9-29.1% neutral detergent fiber. They were enriched in phenolics (by up to 93.4%) and depleted in condensed tannin (by up to 59.3%) in comparison to the raw material. The thin stillages were used for cultivation of edible fungus Neurospora intermedia which produced 8.5-15.9gL(-1) ethanol and 4.8-16.2gL(-1) biomass containing over 62% protein. The mass balances showed that fermentation of unfiltered mashes was more efficient yielding up to 195.9gkg(-1) ethanol and 84.4% of protein recovery.[on SciFinder (R)]
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| 21. |
- Stepniak, Karolina, et al.
(författare)
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Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas. Gliomas are tumors often associated with epigenetics-related gene deregulation. Here the authors reveal an atlas of active enhancers and promoters in benign and malignant gliomas by performing whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples.
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| 22. |
- Williams, Michelle A., et al.
(författare)
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Unipolar Peptidoglycan Synthesis in the Rhizobiales Requires an Essential Class A Penicillin-Binding Protein
- 2021
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Ingår i: mBio. - : ASM International. - 2161-2129 .- 2150-7511. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Members of the Rhizobiales are polarly growing bacteria that lack homologs of the canonical Rod complex. To investigate the mechanisms underlying polar cell wall synthesis, we systematically probed the function of cell wall synthesis enzymes in the plant pathogen Agrobacterium tumefaciens. The development of fluorescent d-amino acid dipeptide (FDAAD) probes, which are incorporated into peptidoglycan by penicillin-binding proteins in A. tumefaciens, enabled us to monitor changes in growth patterns in the mutants. Use of these fluorescent cell wall probes and peptidoglycan compositional analysis demonstrate that a single class A penicillin-binding protein is essential for polar peptidoglycan synthesis. Furthermore, we find evidence of an additional mode of cell wall synthesis that requires ld-transpeptidase activity. Genetic analysis and cell wall targeting antibiotics reveal that the mechanism of unipolar growth is conserved in Sinorhizobium and Brucella. This work provides insights into unipolar peptidoglycan biosynthesis employed by the Rhizobiales during cell elongation.IMPORTANCEWhile the structure and function of the bacterial cell wall are well conserved, the mechanisms responsible for cell wall biosynthesis during elongation are variable. It is increasingly clear that rod-shaped bacteria use a diverse array of growth strategies with distinct spatial zones of cell wall biosynthesis, including lateral elongation, unipolar growth, bipolar elongation, and medial elongation. Yet the vast majority of our understanding regarding bacterial elongation is derived from model organisms exhibiting lateral elongation. Here, we explore the role of penicillin-binding proteins in unipolar elongation of Agrobacterium tumefaciens and related bacteria within the Rhizobiales. Our findings suggest that penicillin-binding protein 1a, along with a subset of ld-transpeptidases, drives unipolar growth. Thus, these enzymes may serve as attractive targets for biocontrol of pathogenic Rhizobiales.
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| 23. |
- Yanofsky, David J., et al.
(författare)
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Structure of mycobacterial CIII2CIV2 respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203)
- 2021
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Ingår i: eLIFE. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed of complexes III and IV (CIII2CIV2). In mycobacterial electron transport chains, CIII2CIV2 replaces canonical CIII and CIV, transferring electrons from the intermediate carrier menaquinol to the final acceptor, molecular oxygen, while simultaneously transferring protons across the inner membrane to power ATP synthesis. We show that telacebec inhibits the menaquinol:oxygen oxidoreductase activity of purified Mycobacterium smegmatis CIII2CIV2 at concentrations similar to those needed to inhibit electron transfer in mycobacterial membranes and Mycobacterium tuberculosis growth in culture. We then used electron cryomicroscopy (cryoEM) to determine structures of CIII2CIV2 both in the presence and absence of telacebec. The structures suggest that telacebec prevents menaquinol oxidation by blocking two different menaquinol binding modes to prevent CIII2CIV2 activity.
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| 24. |
- Zanchetta, Alessandro, et al.
(författare)
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Sources and sinks of carbonyl sulfide inferred from tower and mobile atmospheric observations in the Netherlands
- 2023
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Ingår i: Biogeosciences. - 1726-4170. ; 20:16, s. 3539-3553
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Tidskriftsartikel (refereegranskat)abstract
- Carbonyl sulfide (COS) is a promising tracer for the estimation of terrestrial ecosystem gross primary production (GPP). However, understanding its non-GPP-related sources and sinks, e.g., anthropogenic sources and soil sources and sinks, is also critical to the success of the approach. Here we infer the regional sources and sinks of COS using continuous in situ mole fraction profile measurements of COS along the 60gm tall Lutjewad tower (1gmga.s.l.; 53g 24′gN, 6g 21′gE) in the Netherlands. To identify potential sources that caused the observed enhancements of COS mole fractions at Lutjewad, both discrete flask samples and in situ measurements in the province of Groningen were made from a mobile van using a quantum cascade laser spectrometer (QCLS). We also simulated the COS mole fractions at Lutjewad using the Stochastic Time-Inverted Lagrangian Transport (STILT) model combined with emission inventories and plant uptake fluxes. We determined the nighttime COS fluxes to be -3.0±2.6gpmolgm-2gs-1 using the radon-tracer correlation approach and Lutjewad observations. Furthermore, we identified and quantified several COS sources, including biodigesters, sugar production facilities and silicon carbide production facilities in the province of Groningen. Moreover, the simulation results show that the observed COS enhancements can be partially explained by known industrial sources of COS and CS2, in particular from the Ruhr Valley (51.5gN, 7.2gE) and Antwerp (51.2gN, 4.4gE) areas. The contribution of likely missing anthropogenic sources of COS and CS2 in the inventory may be significant. The impact of the identified sources in the province of Groningen is estimated to be negligible in terms of the observed COS enhancements. However, in specific conditions, these sources may influence the measurements in Lutjewad. These results are valuable for improving our understanding of the sources and sinks of COS, contributing to the use of COS as a tracer for GPP.
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