| 1. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 2. |
- Henkel, C., et al.
(författare)
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Molecular line emission in NGC 4945, imaged with ALMA
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- NGC 4945 is one of the nearest (D ≈ 3.8 Mpc; 1 00 ≈ 19 pc) starburst galaxies. To investigate the structure, dynamics, and composition of the dense nuclear gas of this galaxy, ALMA band 3 (λ ≈ 3−4 mm) observations were carried out with ≈2 00 resolution. Three HCN and two HC + isotopologues, CS, C 3 H 2 , SiO, HCO, and CH 3 C 2 H were measured. Spectral line imaging demonstrates the presence of a rotating nuclear disk of projected size 10 00 × 2 00 reaching out to a galactocentric radius of r ≈ 100 pc with position angle PA = 45 ◦ ± 2 ◦ , inclination i = 75 ◦ ± 2 ◦ and an unresolved bright central core of size <∼ 2 00 . The continuum source, representing mostly free-free radiation from star forming regions, is more compact than the nuclear disk by a linear factor of two but shows the same position angle and is centered 0 00 . 39 ± 0 00 . 14 northeast of the nuclear accretion disk defined by H 2 O maser emission. Near the systemic velocity but outside the nuclear disk, both HCN J = 1 → 0 and CS J = 2 → 1 delineate molecular arms of length >∼ 15 00 ( >∼ 285 pc) on opposite sides of the dynamical center. These are connected by a (deprojected) ≈ 0.6 kpc sized molecular bridge, likely a dense gaseous bar seen almost ends-on, shifting gas from the front and back side into the nuclear disk. Modeling this nuclear disk located farther inside (r <∼ 100 pc) with tilted rings provides a good fit by inferring a coplanar outflow reaching a characteristic deprojected velocity of ≈50 km s −1 . All our molecular lines, with the notable exception of CH 3 C 2 H, show significant absorption near the systemic velocity (≈571 km s −1 ), within the range ≈500-660 km s −1 . Apparently, only molecular transitions with low critical H 2 density (n crit<∼ 10 4 cm −3 ) do not show absorption. The velocity field of the nuclear disk, derived from CH 3 C 2 H, provides evidence for rigid rotation in the inner few arcseconds and a dynamical mass of M tot = (2.1 ± 0.2) × 10 8 M inside a galactocentric radius of 2 00 . 45 (≈45 pc), with a significantly flattened rotation curve farther out. Velocity integrated line intensity maps with most pronounced absorption show molecular peak positions up to ≈1 00 . 5 (≈30 pc) southwest of the continuum peak, presumably due to absorption, which appears to be most severe slightly northeast of the nuclear maser disk. A nitrogen isotope ratio of 14 N/ 15 N ≈ 200-450 is estimated. This range of values is much higher then previously reported on a tentative basis. Therefore, because 15 N is less abundant than expected, the question for strong 15 N enrichment by massive star ejecta in starbursts still remains to be settled.
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| 3. |
- Aharonian, Felix, et al.
(författare)
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Atomic data and spectral modeling constraints from high-resolution X-ray observations of the Perseus cluster with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)abstract
- The Hitomi Soft X-ray Spectrometer spectrum of the Perseus cluster, with similar to 5 eV resolution in the 2-9 keV band, offers an unprecedented benchmark of the atomic modeling and database for hot collisional plasmas. It reveals both successes and challenges of the current atomic data and models. The latest versions of AtomDB/APEC (3.0.8), SPEX (3.03.00), and CHIANTI (8.0) all provide reasonable fits to the broad-band spectrum, and are in close agreement on best-fit temperature, emission measure, and abundances of a few elements such as Ni. For the Fe abundance, the APEC and SPEX measurements differ by 16%, which is 17 times higher than the statistical uncertainty. This is mostly attributed to the differences in adopted collisional excitation and dielectronic recombination rates of the strongest emission lines. We further investigate and compare the sensitivity of the derived physical parameters to the astrophysical source modeling and instrumental effects. The Hitomi results show that accurate atomic data and models are as important as the astrophysical modeling and instrumental calibration aspects. Substantial updates of atomic databases and targeted laboratory measurements are needed to get the current data and models ready for the data from the next Hitomi-level mission.
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| 4. |
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| 5. |
- Wagenaar, Kim P., et al.
(författare)
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Effectiveness of the European Society of Cardiology/Heart Failure Association website heartfailurematters.org and an e-health adjusted care pathway in patients with stable heart failure: results of the e-Vita HF randomized controlled trial
- 2019
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 21:2, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- Background Efficient incorporation of e-health in patients with heart failure (HF) may enhance health care efficiency and patient empowerment. We aimed to assess the effect on self-care of (i) the European Society of Cardiology/Heart Failure Association website on top of usual care, and (ii) an e-health adjusted care pathway leaving out in person routine HF nurse consultations in stable HF patients. Methods and results In a three-group parallel-randomized trial in stable HF patients from nine Dutch outpatient clinics, we compared two interventions ( website and an e-health adjusted care pathway) to usual care. The primary outcome was self-care measured with the European Heart Failure Self-care Behaviour Scale. Secondary outcomes were health status, mortality, and hospitalizations. In total, 450 patients were included. The mean age was 66.8 +/- 11.0 years, 74.2% were male, and 78.8% classified themselves as New York Heart Association I or II at baseline. After 3 months of follow-up, the mean score on the self-care scale was significantly higher in the groups using the website and the adjusted care pathway compared to usual care (73.5 vs. 70.8, 95% confidence interval 0.6-6.2; and 78.2 vs. 70.8, 95% confidence interval 3.8- 9.4, respectively). The effect attenuated, until no differences after 1 year between the groups. Quality of life showed a similar pattern. Other secondary outcomes did not clearly differ between the groups. Conclusions Both the website and an e-health adjusted care pathway improved self-care in HF patients on the short term, but not on the long term. Continuous updating of e-health facilities could be helpful to sustain effects.
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| 6. |
- Aharonian, Felix, et al.
(författare)
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Search for thermal X-ray features from the Crab nebula with the Hitomi soft X-ray spectrometer
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)abstract
- The Crab nebula originated from a core-collapse supernova (SN) explosion observed in 1054 AD. When viewed as a supernova remnant (SNR), it has an anomalously low observed ejecta mass and kinetic energy for an Fe-core-collapse SN. Intensive searches have been made for a massive shell that solves this discrepancy, but none has been detected. An alternative idea is that SN 1054 is an electron-capture (EC) explosion with a lower explosion energy by an order of magnitude than Fe-core-collapse SNe. X-ray imaging searches were performed for the plasma emission from the shell in the Crab outskirts to set a stringent upper limit on the X-ray emitting mass. However, the extreme brightness of the source hampers access to its vicinity. We thus employed spectroscopic technique using the X-ray micro-calorimeter on board the Hitomi satellite. By exploiting its superb energy resolution, we set an upper limit for emission or absorption features from as yet undetected thermal plasma in the 2-12 keV range. We also re-evaluated the existing Chandra and XMM-Newton data. By assembling these results, a new upper limit was obtained for the X-ray plasma mass of less than or similar to 1 M-circle dot for a wide range of assumed shell radius, size, and plasma temperature values both in and out of collisional equilibrium. To compare with the observation, we further performed hydrodynamic simulations of the Crab SNR for two SN models (Fe-core versus EC) under two SN environments (uniform interstellar medium versus progenitor wind). We found that the observed mass limit can be compatible with both SN models if the SN environment has a low density of less than or similar to 0.03 cm(-3) (Fe core) or less than or similar to 0.1 cm(-3) (EC) for the uniform density, or a progenitor wind density somewhat less than that provided by amass loss rate of 10(-5) M-circle dot yr(-1) at 20 km s(-1) for the wind environment.
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| 7. |
- Chen, Que, et al.
(författare)
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Combining retinal-based and chlorophyll-based (oxygenic) photosynthesis : Proteorhodopsin expression increases growth rate and fitness of a Delta PSI strain of Synechocystis sp. PCC6803
- 2019
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Ingår i: Metabolic engineering. - : Elsevier. - 1096-7176 .- 1096-7184. ; 52, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- To fill the "green absorption gap", a green absorbing proteorhodopsin was expressed in a PSI-deletion strain (Delta PSI) of Synechocystis sp. PCC6803. Growth-rate measurements, competition experiments and physiological characterization of the proteorhodopsin-expressing strains, relative to the Delta PSI control strain, allow us to conclude that proteorhodopsin can enhance the rate of photoheterotrophic growth of Delta PSI Synechocystis strain. The physiological characterization included measurement of the amount of residual glucose in the spent medium and analysis of oxygen uptake- and production rates. To explore the use of solar radiation beyond the PAR region, a red-shifted variant Proteorhodopsin-D212N/F234S was expressed in a retinal-deficient PSI-deletion strain (Delta PSI/Delta SynACO). Via exogenous addition of retinal analogue an infrared absorbing pigment (maximally at 740 nm) was reconstituted in vivo. However, upon illumination with 746 nm light, it did not significantly stimulate the growth (rate) of this mutant. The inability of the proteorhodopsin-expressing Delta PSI strain to grow photoautotrophically is most likely due to a kinetic rather than a thermodynamic limitation of its NADPH-dehydrogenase in NADP(+)-reduction.
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| 8. |
- Chen, Que, et al.
(författare)
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Functional Expression of Gloeobacter Rhodopsin in PSI-Less Synechocystis sp. PCC6803
- 2019
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The approach of providing an oxygenic photosynthetic organism with a cyclic electron transfer system, i.e., a far-red light-driven proton pump, is widely proposed to maximize photosynthetic efficiency via expanding the absorption spectrum of photosynthetically active radiation. As a first step in this approach, Gloeobacter rhodopsin was expressed in a PSI-deletion strain of Synechocystis sp. PCC6803. Functional expression of Gloeobacter rhodopsin, in contrast to Proteorhodopsin, did not stimulate the rate of photoheterotrophic growth of this Synechocystis strain, analyzed with growth rate measurements and competition experiments. Nevertheless, analysis of oxygen uptake and-production rates of the Gloeobacter rhodopsin-expressing strains, relative to the 1 PSI control strain, confirm that the proton-pumping Gloeobacter rhodopsin provides the cells with additional capacity to generate proton motive force. Significantly, expression of the Gloeobacter rhodopsin did modulate levels of pigment formation in the transgenic strain.
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| 9. |
- Claassens, Nico J., et al.
(författare)
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Bicistronic Design-Based Continuous and High-Level Membrane Protein Production in Escherichia coil
- 2019
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Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 8:7, s. 1685-1690
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli has been widely used as a platform microorganism for both membrane protein production and cell factory engineering. The current methods to produce membrane proteins in this organism require the induction of target gene expression and often result in unstable, low yields. Here, we present a method combining a constitutive promoter with a library of bicistronic design (BCD) elements, which enables inducer-free, tuned translation initiation for optimal protein production. Our system mediates stable, constitutive production of bacterial membrane proteins at yields that outperform those obtained with E. coli Lemo21(DE3), the current gold standard for bacterial membrane protein production. We envisage that the continuous, fine-tunable, and high-level production of membrane proteins by our method will greatly facilitate their study and their utilization in engineering cell factories.
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| 10. |
- De Boer, Hugo J., et al.
(författare)
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Molecular phylogenetic analyses of Cucurbitaceae tribe Benincaseae urge for merging of Pilogyne with Zehneria
- 2015
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Ingår i: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 236:2, s. 173-183
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Tidskriftsartikel (refereegranskat)abstract
- The tropical cucurbitaceous genus Zehneria as traditionally circumscribed displays much morphological diversity. Recent taxonomic revisions have resulted in its redefinition through both recognition and subsequent lumping of several additional genera. This study utilized plastid and nuclear DNA sequence data to reconstruct a molecular phylogeny of Zehneria and its close relatives in order to test whether these revisions reflected the molecular evolution in this group. The results suggest that Neoachmandra is monophyletic, and that Zehneria in a restricted sense and Neoachmandra accessions form a single monophyletic clade, whereas Pilogyne in its present understanding is polyphyletic. In the light of these results Pilogyne should be merged back into Zehneria from which it was split off earlier.
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