| 1. |
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| 2. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
- Garcia-Benito, R., et al.
(författare)
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CALIFA, the Calar Alto Legacy Integral Field Area survey III. Second public data release
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576:A135
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the Second Public Data Release (DR2) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. The data for 200 objects are made public, including the 100 galaxies of the First Public Data Release (DR1). Data were obtained with the integral-field spectrograph PMAS /PPak mounted on the 3.5 m telescope at the Calar Alto observatory. Two different spectral setups are available for each galaxy, (i) a low-resolution V500 setup covering the wavelength range 3745-7500 angstrom with a spectral resolution of 6.0 angstrom (FWHM); and (ii) a medium-resolution V1200 setup covering the wavelength range 3650-4840 angstrom with a spectral resolution of 2.3 angstrom (FWHM). The sample covers a redshift range between 0.005 and 0.03, with a wide range of properties in the color-magnitude diagram, stellar mass, ionization conditions, and morphological types. All the cubes in the data release were reduced with the latest pipeline, which includes improved spectrophotometric calibration, spatial registration, and spatial resolution. The spectrophotometric calibration is better than 6% and the median spatial resolution is 2 4. In total, the second data release contains over 1.5 million spectra.
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| 4. |
- Molina, F., et al.
(författare)
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Tz=-1 → 0 β-Decays of 54Ni, 50Fe, 46Cr, and 42Ti and Comparison With Mirror (3He,t) Measurements
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:1
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the β decay of the Tz=−1, f7/2 shell nuclei Ni54, Fe50, Cr46, and Ti42 produced in fragmentation reactions. The proton separation energies in the daughter Tz=0 nuclei are relatively large (≈4–5 MeV) so studies of the γ rays are essential. The experiments were performed at GSI as part of the Stopped-beam campaign with the RISING setup consisting of 15 Euroball Cluster Ge detectors. From the newly obtained high precision β-decay half-lives, excitation energies, and β branching ratios, we were able to extract Fermi and Gamow-Teller transition strengths in these β decays. With these improved results it was possible to compare in detail the Gamow-Teller (GT) transition strengths observed in beta decay including a sensitivity limit with the strengths of the Tz=+1 to Tz=0 transitions derived from high resolution (3He,t) reactions on the mirror target nuclei at RCNP, Osaka. The accumulated B(GT) strength obtained from both experiments looks very similar although the charge exchange reaction provides information on a broader energy range. Using the “merged analysis” one can obtain a full picture of the B(GT) over the full Qβ range. Looking at the individual transitions some differences are observed, especially for the weak transitions. Their possible origins are discussed.
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| 5. |
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| 6. |
- Olofsson, J., et al.
(författare)
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Resolving faint structures in the debris disk around TWA 7 Tentative detections of an outer belt, a spiral arm, and a dusty cloud
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- Context. Debris disks are the intrinsic by-products of the star and planet formation processes. Most likely due to instrumental limitations and their natural faintness, little is known about debris disks around low mass stars, especially when it comes to spatially resolved observations. Aims. We present new VLT/SPHERE IRDIS dual-polarization imaging (DPI) observations in which we detect the dust ring around the M2 spectral type star TWA 7. Combined with additional angular differential imaging observations we aim at a fine characterization of the debris disk and setting constraints on the presence of low-mass planets. Methods. We modeled the SPHERE DPI observations and constrain the location of the small dust grains, as well as the spectral energy distribution of the debris disk, using the results inferred from the observations, and performed simple N-body simulations. Results. We find that the dust density distribution peaks at similar to 0.72 '' (25 au), with a very shallow outer power-law slope, and that the disk has an inclination of similar to 13 degrees with a position angle of similar to 91 degrees east of north. We also report low signal-to-noise ratio detections of an outer belt at a distance of similar to 1.5 '' (similar to 52 au) from the star, of a spiral arm in the southern side of the star, and of a possible dusty clump at 0.11 ''. These findings seem to persist over timescales of at least a year. Using the intensity images, we do not detect any planets in the close vicinity of the star, but the sensitivity reaches Jovian planet mass upper limits. We find that the SED is best reproduced with an inner disk at similar to 0.2 '' (similar to 7 au) and another belt at 0.72 '' (25 au). Conclusions. We report the detections of several unexpected features in the disk around TWA 7. A yet undetected 100 M-circle plus planet with a semi-major axis at 20-30 au could possibly explain the outer belt as well as the spiral arm. We conclude that stellar winds are unlikely to be responsible for the spiral arm.
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| 7. |
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| 8. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Fuchs, A., et al.
(författare)
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Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.
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| 10. |
- Olofsson, J., et al.
(författare)
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Azimuthal asymmetries in the debris disk around HD61005 A massive collision of planetesimals?
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 591
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Tidskriftsartikel (refereegranskat)abstract
- Context. Debris disks off er valuable insights into the latest stages of circumstellar disk evolution, and can possibly help us to trace the outcomes of planetary formation processes. In the age range 10 to 100 Myr, most of the gas is expected to have been removed from the system, giant planets (if any) must have already been formed, and the formation of terrestrial planets may be on-going. Pluto-sized planetesimals, and their debris released in a collisional cascade, are under their mutual gravitational influence, which may result into non-axisymmetric structures in the debris disk. Aims. High angular resolution observations are required to investigate these effects and constrain the dynamical evolution of debris disks. Furthermore, multi-wavelength observations can provide information about the dust dynamics by probing different grain sizes. Methods. Here we present new VLT/SPHERE and ALMA observations of the debris disk around the 40 Myr-old solar-type star HD61005. We resolve the disk at unprecedented resolution both in the near-infrared (in scattered and polarized light) and at millimeter wavelengths. We perform a detailed modeling of these observations, including the spectral energy distribution. Results. Thanks to the new observations, we propose a solution for both the radial and azimuthal distribution of the dust grains in the debris disk. We find that the disk has a moderate eccentricity (e similar to 0.1) and that the dust density is two times larger at the pericenter compared to the apocenter. Conclusions. With no giant planets detected in our observations, we investigate alternative explanations besides planet-disk interactions to interpret the inferred disk morphology. We postulate that the morphology of the disk could be the consequence of a massive collision between similar to 1000 km-sized bodies at similar to 61 au. If this interpretation holds, it would put stringent constraints on the formation of massive planetesimals at large distances from the star.
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| 11. |
- Caceres, L., et al.
(författare)
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Nuclear structure studies of F-24
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:1
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the F-24 nucleus has been studied at GANIL using the beta decay of O-24 and the in-beam.-ray spectroscopy from the fragmentation of Na-27,Na-28, Ne-25,Ne-26, and Mg-29,Mg-30 nuclei. Combining these complementary experimental techniques, the level scheme of F-24 has been constructed up to 3.6 MeV by means of particle-gamma and particle-gamma gamma coincidence relations. Experimental results are compared to shell-model calculations using the standard USDA and USDB interactions as well as ab initio valence-space Hamiltonians calculated from the in-medium similarity renormalization group based on chiral two- and three-nucleon forces. Both methods reproduce the measured level spacings well, and this close agreement allows unidentified spins and parities to be consistently assigned.
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| 12. |
- Ahlström, A. P., et al.
(författare)
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Historically unprecedented global glacier decline in the early 21st century
- 2015
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Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 61:228, s. 745-
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Tidskriftsartikel (refereegranskat)abstract
- Observations show that glaciers around the world are in retreat and losing mass. Internationally coordinated for over a century, glacier monitoring activities provide an unprecedented dataset of glacier observations from ground, air and space. Glacier studies generally select specific parts of these datasets to obtain optimal assessments of the mass-balance data relating to the impact that glaciers exercise on global sea-level fluctuations or on regional runoff. In this study we provide an overview and analysis of the main observational datasets compiled by the World Glacier Monitoring Service (WGMS). The dataset on glacier front variations (similar to 42 000 since 1600) delivers clear evidence that centennial glacier retreat is a global phenomenon. Intermittent readvance periods at regional and decadal scale are normally restricted to a subsample of glaciers and have not come close to achieving the maximum positions of the Little Ice Age (or Holocene). Glaciological and geodetic observations (similar to 5200 since 1850) show that the rates of early 21st-century mass loss are without precedent on a global scale, at least for the time period observed and probably also for recorded history, as indicated also in reconstructions from written and illustrated documents. This strong imbalance implies that glaciers in many regions will very likely suffer further ice loss, even if climate remains stable.
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| 13. |
- Charman, Tony, et al.
(författare)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers.METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms.RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females.CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials.
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| 14. |
- Hock, R, et al.
(författare)
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High Mountain Areas
- 2019
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Ingår i: IPCC Special Report on the Ocean and Cryosphere in a Changing Climate. - : IPCC - Intergovernmental Panel on Climate Change. ; , s. 131-202
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The cryosphere (including, snow, glaciers, permafrost, lake and river ice) is an integral element of high- mountain regions, which are home to roughly 10% of the global population. Widespread cryosphere changes affect physical, biological and human systems in the mountains and surrounding lowlands, with impacts evident even in the ocean. Building on the IPCC’s Fifth Assessment Report (AR5), this chapter assesses new evidence on observed recent and projected changes in the mountain cryosphere as well as associated impacts, risks and adaptation measures related to natural and human systems. Impacts in response to climate changes independently of changes in the cryosphere are not assessed in this chapter. Polar mountains are included in Chapter 3, except those in Alaska and adjacent Yukon, Iceland, and Scandinavia, which are included in this chapter.
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| 15. |
- Loth, Eva, et al.
(författare)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD.METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability.RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted).CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.
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| 16. |
- Aparicio, Francisco J., et al.
(författare)
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Dye-based photonic sensing systems
- 2016
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 228, s. 649-657
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Tidskriftsartikel (refereegranskat)abstract
- We report on dye-based photonic sensing systems which are fabricated and packaged at wafer scale. For the first time luminescent organic nanocomposite thin-films deposited by plasma technology are integrated in photonic sensing systems as active sensing elements. The realized dye-based photonic sensors include an environmental NO2 sensor and a sunlight ultraviolet light (UV) A+B sensor. The luminescent signal from the nanocomposite thin-films responds to changes in the environment and is selectively filtered by a photonic structure consisting of a Fabry-Perot cavity. The sensors are fabricated and packaged at wafer-scale, which makes the technology viable for volume manufacturing. Prototype photonic sensor systems have been tested in real-world scenarios. (C) 2016 Elsevier B.V. All rights reserved.
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| 17. |
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| 18. |
- Fuente-Martin, E., et al.
(författare)
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Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Hypothalamic astrocytes can respond to metabolic signals, such as leptin and insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin regulates appetite, adiposity and glucose metabolism, but little is known regarding the response of astrocytes to this orexigenic hormone. We have used both in vivo and in vitro approaches to demonstrate that acylated ghrelin (acyl-ghrelin) rapidly stimulates glutamate transporter expression and glutamate uptake by astrocytes. Moreover, acyl-ghrelin rapidly reduces glucose transporter (GLUT) 2 levels and glucose uptake by these glial cells. Glutamine synthetase and lactate dehydrogenase decrease, while glycogen phosphorylase and lactate transporters increase in response to acyl-ghrelin, suggesting a change in glutamate and glucose metabolism, as well as glycogen storage by astrocytes. These effects are partially mediated through ghrelin receptor 1A (GHSR-1A) as astrocytes do not respond equally to desacyl-ghrelin, an isoform that does not activate GHSR-1A. Moreover, primary astrocyte cultures from GHSR-1A knock-out mice do not change glutamate transporter or GLUT2 levels in response to acyl-ghrelin. Our results indicate that acyl-ghrelin may mediate part of its metabolic actions through modulation of hypothalamic astrocytes and that this effect could involve astrocyte mediated changes in local glucose and glutamate metabolism that alter the signals/nutrients reaching neighboring neurons.
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| 19. |
- James, Rory Hennell, et al.
(författare)
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Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus ` Caldiarchaeum subterraneum' operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor.
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| 20. |
- Narrowe, Adrienne B., et al.
(författare)
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Complex Evolutionary History of Translation Elongation Factor 2 and Diphthamide Biosynthesis in Archaea and Parabasalids
- 2018
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 10:9, s. 2380-2393
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Tidskriftsartikel (refereegranskat)abstract
- Diphthamide is a modified histidine residue which is uniquely present in archaeal and eukaryotic elongation factor 2 (EF-2), an essential GTPase responsible for catalyzing the coordinated translocation of tRNA and mRNA through the ribosome. In part due to the role of diphthamide in maintaining translational fidelity, it was previously assumed that diphthamide biosynthesis genes (dph) are conserved across all eukaryotes and archaea. Here, comparative analysis of new and existing genomes reveals that some archaea (i.e., members of the Asgard superphylum, Geoarchaea, and Korarchaeota) and eukaryotes (i.e., parabasalids) lack dph. In addition, while EF-2 was thought to exist as a single copy in archaea, many of these dph-lacking archaeal genomes encode a second EF-2 paralog missing key residues required for diphthamide modification and for normal translocase function, perhaps suggesting functional divergence linked to loss of diphthamide biosynthesis. Interestingly, some Heimdallarchaeota previously suggested to be most closely related to the eukaryotic ancestor maintain dph genes and a single gene encoding canonical EF-2. Our findings reveal that the ability to produce diphthamide, once thought to be a universal feature in archaea and eukaryotes, has been lost multiple times during evolution, and suggest that anticipated compensatory mechanisms evolved independently.
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| 21. |
- Zaremba-Niedzwiedzka, Katarzyna, et al.
(författare)
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Asgard archaea illuminate the origin of eukaryotic cellular complexity
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7637, s. 353-
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Tidskriftsartikel (refereegranskat)abstract
- The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal phylum with many eukaryotic features. The emergence of the structural complexity that characterizes eukaryotic cells remains unclear. Here we describe the 'Asgard' superphylum, a group of uncultivated archaea that, as well as Lokiarchaeota, includes Thor-, Odin- and Heimdallarchaeota. Asgard archaea affiliate with eukaryotes in phylogenomic analyses, and their genomes are enriched for proteins formerly considered specific to eukaryotes. Notably, thorarchaeal genomes encode several homologues of eukaryotic membrane-trafficking machinery components, including Sec23/24 and TRAPP domains. Furthermore, we identify thorarchaeal proteins with similar features to eukaryotic coat proteins involved in vesicle biogenesis. Our results expand the known repertoire of 'eukaryote-specific' proteins in Archaea, indicating that the archaeal host cell already contained many key components that govern eukaryotic cellular complexity.
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| 22. |
- Arrizabalaga, O., et al.
(författare)
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High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response
- 2017
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC. Notably, we find that high levels of MKP1 correlate with a subset of glioblastoma patients with better prognosis and overall increased survival. Gain of expression studies demonstrated that elevated MKP1 impairs self-renewal and induces differentiation of GSCs while reducing tumorigenesis in vivo. Moreover, we identified that MKP1 is epigenetically regulated and that it mediates the anti-tumor activity of histone deacetylase inhibitors (HDACIs) alone or in combination with temozolomide. In summary, this study identifies MKP1 as a key modulator of the interplay between GSC self-renewal and differentiation and provides evidence that the activation of MKP1, through epigenetic regulation, might be a novel therapeutic strategy to overcome therapy resistance in glioblastoma.
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| 23. |
- Caceres, Eva F.
(författare)
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Genomic and evolutionary exploration of Asgard archaea
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Current evolutionary theories postulate that eukaryotes emerged from the symbiosis of an archaeal host with, at least, one bacterial symbiont. However, our limited grasp of microbial diversity hampers insights into the features of the prokaryotic ancestors of eukaryotes. This thesis focuses on the study of a group of uncultured archaea to better understand both existing archaeal diversity and the origin of eukaryotes.In a first study, we used short-read metagenomic approaches to obtain eight genomes of Lokiarchaeum relatives. Using these data we described the Asgard superphylum, comprised of at least four different phyla: Lokiarchaeota, Odinarchaeota, Thorarchaeota and Heimdallarchaoeta. Phylogenetic analyses suggested that eukaryotes affiliate with the Asgard group, albeit the exact position of eukaryotes with respect to Asgard archaea members remained inconclusive. Comparative genomics showed that Asgard archaea genomes encoded homologs of numerous eukaryotic signature proteins (ESPs), which had never been observed in Archaea before. Among these, there were several components of proteins involved in vesicle formation and membrane remodelling.In a second study, we used similar approaches to uncover additional members of the Asgard superphylum. Based on genome-centric metagenomics we recovered 69 new genomes from which we identified five additional candidate phyla: Freyarchaeota, Baldrarchaeota, Gefionarchaeota, Friggarchaeota and Idunnarchaeota. In this expanded dataset we could detect additional homologs for unreported ESPs. Updated phylogenies showed support for a scenario in which eukaryotes emerged from within Asgard archaea.We further took advantage of the increased Asgard diversity to delimit the gene content of the last common archaeal ancestor of eukaryotes using ancestral reconstruction analyses. The results suggest that the archaeal host cell who gave rise to eukaryotes already contained many of the genes associated with eukaryotic cellular complexity. Based on these analyses, we discussed the metabolic capabilities of the archaeal ancestor of eukaryotes.Finally, we reconstructed several nearly complete Lokiarchaeota genomes, one of them in only three contigs, using both short- and long-read metagenomics. These analyses indicate that long-read metagenomics is a promising approach to obtain highly complete and contiguous genomes directly from environmental samples, even from complex populations in the presence of microdiversity and low abundant members. This study further supports that the presence of ESPs in Asgard genomes is not the result of assembly and binning artefacts. In conclusion, this thesis highlights the value of using culture-independent approaches together with phylogenomics and comparative genomics to improve our understanding of microbial diversity and to shed light into relevant evolutionary questions.
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| 24. |
- Gomez-Velazquez, Melisa, et al.
(författare)
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CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart
- 2017
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.
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| 25. |
- Marshall, Ian P. G., et al.
(författare)
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The novel bacterial phylum Calditrichaeota is diverse, widespread and abundant in marine sediments and has the capacity to degrade detrital proteins
- 2017
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Ingår i: Environmental Microbiology Reports. - : Wiley. - 1758-2229. ; 9:4, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- Calditrichaeota is a recently recognized bacterial phylum with three cultured representatives, isolated from hydrothermal vents. Here we expand the phylogeny and ecology of this novel phylum with metagenome-derived and single-cell genomes from six uncultivated bacteria previously not recognized as members of Calditrichaeota. Using 16S rRNA gene sequences from these genomes, we then identified 322 16S rRNA gene sequences from cultivation-independent studies that can now be classified as Calditrichaeota for the first time. This dataset was used to re-analyse a collection of 16S rRNA gene amplicon datasets from marine sediments showing that the Calditrichaeota are globally distributed in the seabed at high abundance, making up to 6.7% of the total bacterial community. This wide distribution and high abundance of Calditrichaeota in cold marine sediment has gone unrecognized until now. All Calditrichaeota genomes show indications of a chemoorganoheterotrophic metabolism with the potential to degrade detrital proteins through the use of extracellular peptidases. Most of the genomes contain genes encoding proteins that confer O-2 tolerance, consistent with the relatively high abundance of Calditrichaeota in surficial bioturbated part of the seabed and, together with the genes encoding extracellular peptidases, suggestive of a general ecophysiological niche for this newly recognized phylum in marine sediment.
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| 26. |
- Pascual, Unai, et al.
(författare)
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Valuing nature's contributions to people : the IPBES approach
- 2017
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435. ; 26-27, s. 7-16
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Forskningsöversikt (refereegranskat)abstract
- Nature is perceived and valued in starkly different and often conflicting ways. This paper presents the rationale for the inclusive valuation of nature's contributions to people (NCP) in decision making, as well as broad methodological steps for doing so. While developed within the context of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES), this approach is more widely applicable to initiatives at the knowledge–policy interface, which require a pluralistic approach to recognizing the diversity of values. We argue that transformative practices aiming at sustainable futures would benefit from embracing such diversity, which require recognizing and addressing power relationships across stakeholder groups that hold different values on human nature-relations and NCP.
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| 27. |
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| 28. |
- Spang, Anja, et al.
(författare)
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Genomic exploration of the diversity, ecology, and evolution of the archaeal domain of life.
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 357:6351
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Forskningsöversikt (refereegranskat)abstract
- About 40 years ago, Archaea were recognized as a major prokaryotic domain of life besides Bacteria. Recently, cultivation-independent sequencing methods have produced a wealth of genomic data for previously unidentified archaeal lineages, several of which appear to represent newly revealed branches in the tree of life. Analyses of some recently obtained genomes have uncovered previously unknown metabolic traits and provided insights into the evolution of archaea and their relationship to eukaryotes. On the basis of our current understanding, much archaeal diversity still defies genomic exploration. Efforts to obtain and study genomes and enrichment cultures of uncultivated microbial lineages will likely further expand our knowledge about archaeal phylogenetic and metabolic diversity and their cell biology and ecological function.
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| 29. |
- Spang, Anja, et al.
(författare)
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Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism
- 2019
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 4:7, s. 1138-1148
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Tidskriftsartikel (refereegranskat)abstract
- The origin of eukaryotes represents an unresolved puzzle in evolutionary biology. Current research suggests that eukaryotes evolved from a merger between a host of archaeal descent and an alphaproteobacterial endosymbiont. The discovery of the Asgard archaea, a proposed archaeal superphylum that includes Lokiarchaeota, Thorarchaeota, Odinarchaeota and Heimdallarchaeota suggested to comprise the closest archaeal relatives of eukaryotes, has helped to elucidate the identity of the putative archaeal host. Whereas Lokiarchaeota are assumed to employ a hydrogen-dependent metabolism, little is known about the metabolic potential of other members of the Asgard superphylum. We infer the central metabolic pathways of Asgard archaea using comparative genomics and phylogenetics to be able to refine current models for the origin of eukaryotes. Our analyses indicate that Thorarchaeota and Lokiarchaeota encode proteins necessary for carbon fixation via the Wood-Ljungdahl pathway and for obtaining reducing equivalents from organic substrates. By contrast, Heimdallarchaeum LC2 and LC3 genomes encode enzymes potentially enabling the oxidation of organic substrates using nitrate or oxygen as electron acceptors. The gene repertoire of Heimdallarchaeum AB125 and Odinarchaeum indicates that these organisms can ferment organic substrates and conserve energy by coupling ferredoxin reoxidation to respiratory proton reduction. Altogether, our genome analyses suggest that Asgard representatives are primarily organoheterotrophs with variable capacity for hydrogen consumption and production. On this basis, we propose the 'reverse flow model', an updated symbiogenetic model for the origin of eukaryotes that involves electron or hydrogen flow from an organoheterotrophic archaeal host to a bacterial symbiont.
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| 30. |
- Trzonkowski, Piotr, et al.
(författare)
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Hurdles in therapy with regulatory T cells
- 2015
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 7:304
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Tidskriftsartikel (refereegranskat)abstract
- Improper activation of the immune system contributes to a variety of clinical conditions, including autoimmune and allergic diseases as well as solid organ and bone marrow transplantation. One approach to counteract this activation is through adoptive therapy with regulatory T cells (T-regs). Efforts to manufacture these cells have led to good maunfacturing practice-compliant protocols, and T-reg products are entering early clinical trials. Here, we report the stance of the European Union Cooperation in Science and Technology Action BM1305, "Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies-A FACTT," which identifies hurdles hindering T-reg clinical applications in Europe and provides possible solutions.
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| 31. |
- Welearegay, T. G., et al.
(författare)
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Ultrapure Organically Modified Gold Nanoparticles for Breath Analysis
- 2016
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Ingår i: Procedia Engineering. - : Elsevier BV. - 1877-7058. ; 168, s. 133-136
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Tidskriftsartikel (refereegranskat)abstract
- In this study we present a new technological approach for the fabrication of ultrapure organically modified gold nanoparticles (AuNPs) for chemical sensing applied to exhaled breath analysis. To achieve a high purity level of the sensing films, we combined Advanced Gas Deposition (AGD) technique to deposit ultrapure monodispersed AuNPs, and dip coating process for functionalization of the AuNPs with thiolated organic ligands. Morphology and surface analysis revealed the deposition of ultrapure isolated AuNPs after the first processing step, and a network of nanoparticle–ligand nanoassemblies after the second processing step. Gas sensing measurements were performed with exhaled breath samples collected from a group of smokers, a group of non-smokers, and ambient air. Sensors responses towards these samples demonstrated characteristic responses for each study group. PCA analysis further revealed samples classification in three distinct characteristic clusters, which indicates the suitability of the molecularly modified AuNPs presented in this communication for breath analysis applications.
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