| 1. |
- Lagou, Vasiliki, et al.
(författare)
-
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
|
|
| 2. |
- Ebersole, Charles R., et al.
(författare)
-
Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
-
Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
|
|
| 3. |
- Bajusz, Csaba, et al.
(författare)
-
The nuclear activity of the actin-binding Moesin protein is necessary for gene expression in Drosophila
- 2021
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 288:16, s. 4812-4832
-
Tidskriftsartikel (refereegranskat)abstract
- Ezrin-Radixin-Moesin (ERM) proteins play an essential role in the cytoplasm by cross-linking actin filaments with plasma membrane proteins. Research has identified the nuclear localization of ERMs, as well as the involvement of a single Drosophila ERM protein, Moesin, in nuclear mRNA exports. However, the question of how important the nuclear activity of ERM proteins are for the life of an organism has so far not been explored. Here, we present the first attempt to reveal the in vivo relevance of nuclear localization of Moesin in Drosophila. With the help of a nuclear export signal, we decreased the amount of Moesin in the nuclei of the animals. Furthermore, we observed various developmental defects, demonstrating the importance of ERM function in the nucleus for the first time. Transcriptome analysis of the mutant flies revealed that the lack of nuclear Moesin function leads to expression changes in nearly 700 genes, among them heat-shock genes. This result together with additional findings revealed that in Drosophila the expression of protein chaperones requires the nuclear functions of Moesin.
|
|
| 4. |
|
|
| 5. |
- Benz, W., et al.
(författare)
-
The CHEOPS mission
- 2021
-
Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51:1, s. 109-151
-
Tidskriftsartikel (refereegranskat)abstract
- The CHaracterising ExOPlanet Satellite (CHEOPS) was selected on October 19, 2012, as the first small mission (S-mission) in the ESA Science Programme and successfully launched on December 18, 2019, as a secondary passenger on a Soyuz-Fregat rocket from Kourou, French Guiana. CHEOPS is a partnership between ESA and Switzerland with important contributions by ten additional ESA Member States. CHEOPS is the first mission dedicated to search for transits of exoplanets using ultrahigh precision photometry on bright stars already known to host planets. As a follow-up mission, CHEOPS is mainly dedicated to improving, whenever possible, existing radii measurements or provide first accurate measurements for a subset of those planets for which the mass has already been estimated from ground-based spectroscopic surveys. The expected photometric precision will also allow CHEOPS to go beyond measuring only transits and to follow phase curves or to search for exo-moons, for example. Finally, by unveiling transiting exoplanets with high potential for in-depth characterisation, CHEOPS will also provide prime targets for future instruments suited to the spectroscopic characterisation of exoplanetary atmospheres. To reach its science objectives, requirements on the photometric precision and stability have been derived for stars with magnitudes ranging from 6 to 12 in the V band. In particular, CHEOPS shall be able to detect Earth-size planets transiting G5 dwarf stars (stellar radius of 0.9R⊙) in the magnitude range 6 ≤ V ≤ 9 by achieving a photometric precision of 20 ppm in 6 hours of integration time. In the case of K-type stars (stellar radius of 0.7R⊙) of magnitude in the range 9 ≤ V ≤ 12, CHEOPS shall be able to detect transiting Neptune-size planets achieving a photometric precision of 85 ppm in 3 hours of integration time. This precision has to be maintained over continuous periods of observation for up to 48 hours. This precision and stability will be achieved by using a single, frame-transfer, back-illuminated CCD detector at the focal plane assembly of a 33.5 cm diameter, on-axis Ritchey-Chrétien telescope. The nearly 275 kg spacecraft is nadir-locked, with a pointing accuracy of about 1 arcsec rms, and will allow for at least 1 Gbit/day downlink. The sun-synchronous dusk-dawn orbit at 700 km altitude enables having the Sun permanently on the backside of the spacecraft thus minimising Earth stray light. A mission duration of 3.5 years in orbit is foreseen to enable the execution of the science programme. During this period, 20% of the observing time is available to the wider community through yearly ESA call for proposals, as well as through discretionary time approved by ESA’s Director of Science. At the time of this writing, CHEOPS commissioning has been completed and CHEOPS has been shown to fulfill all its requirements. The mission has now started the execution of its science programme.
|
|
| 6. |
- Ekroos, Johan, et al.
(författare)
-
High land-use intensity in grasslands constrains wild bee species richness in Europe
- 2020
-
Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 241
-
Tidskriftsartikel (refereegranskat)abstract
- There is widespread concern regarding declines in bee populations given their importance for the functioning of both natural and managed ecosystems. An increasing number of studies find negative relations between bee species richness and simplification of agricultural landscapes, but the role of land-use intensity and its relative importance compared to landscape simplification remain less clear. We compared the relative effects of nitrogen inputs, as a proxy for land-use intensity, and proportion of natural and semi-natural habitat, as a measure of landscape complexity on total bee species richness, rare species richness and dominant crop-visiting species richness. We used data from 282 grasslands across five countries, covering the entire range of low intensity, no-input systems, to high-input sites (>400 kg N/ha/year). We found consistent negative impacts of increasing land-use intensity at a regional scale on total bee species richness and dominant crop-visiting species across Europe, but no such effects of landscape complexity. In contrast, the richness of rare bee species was not significantly related to increasing land-use intensity. Nevertheless, based on species accumulation curves, grasslands with no nitrogen inputs had higher total bee richness and higher shares of rare species compared with sites with high nitrogen inputs (>125 kg N/ha/year). Our results highlight the importance of retaining grasslands characterised by low land-use intensity across agricultural landscapes to promote bee diversity.
|
|
| 7. |
- Engqvist, Hanna, 1985, et al.
(författare)
-
Integrative genomics approach identifies molecular features associated with early-stage ovarian carcinoma histotypes.
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer comprises multiple subtypes (clear-cell (CCC), endometrioid (EC), high-grade serous (HGSC), low-grade serous (LGSC), and mucinous carcinomas (MC)) with differing molecular and clinical behavior. However, robust histotype-specific biomarkers for clinical use have yet to be identified. Here, we utilized a multi-omics approach to identify novel histotype-specific genetic markers associated with ovarian carcinoma histotypes (CCC, EC, HGSC, and MC) using DNA methylation, DNA copy number alteration and RNA sequencing data for 96 primary invasive early-stage (stage I and II) ovarian carcinomas. More specifically, the DNA methylation analysis revealed hypermethylation for CCC in comparison with the other histotypes. Moreover, copy number imbalances and novel chromothripsis-like rearrangements (n=64) were identified in ovarian carcinoma, with the highest number of chromothripsis-like patterns in HGSC. For the 1000 most variable transcripts, underexpression was most prominent for all histotypes in comparison with normal ovarian samples. Overall, the integrative approach identified 46 putative oncogenes (overexpressed, hypomethylated and DNA gain) and three putative tumor suppressor genes (underexpressed, hypermethylated and DNA loss) when comparing the different histotypes. In conclusion, the current study provides novel insights into molecular features associated with early-stage ovarian carcinoma that may improve patient stratification and subclassification of the histotypes.
|
|
| 8. |
- Garratt, Michael P D, et al.
(författare)
-
Opportunities to reduce pollination deficits and address production shortfalls in an important insect pollinated crop
- 2021
-
Ingår i: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582.
-
Tidskriftsartikel (refereegranskat)abstract
- Pollinators face multiple pressures and there is evidence of populations in decline. As demand for insect-pollinated crops increases, crop production is threatened by shortfalls in pollination services. Understanding the extent of current yield deficits due to pollination and identifying opportunities to protect or improve crop yield and quality through pollination management is therefore of international importance. To explore the extent of 'pollination deficits', where maximum yield is not being achieved due to insufficient pollination, we use an extensive dataset on a globally important crop, apples. We quantified how these deficits vary between orchards and countries as well as compare 'pollinator dependence' across different apple varieties. We found evidence of pollination deficits and in some cases, risks of over-pollination were even apparent where fruit quality could be reduced by too much pollination. In almost all regions studied we found some orchards performing significantly better than others, in terms of avoiding a pollination deficit and crop yield shortfalls due to sub-optimal pollination. This represents an opportunity to improve production through better pollinator and crop management. Our findings also demonstrate that pollinator dependence varies considerably between apple varieties in terms of fruit number and fruit quality. We propose that assessments of pollination service and deficits in crops can be used to quantify supply and demand for pollinators and help target local management to address deficits although crop variety has a strong influence on the role of pollinators.
|
|
| 9. |
- Hatos, Andras, et al.
(författare)
-
DisProt : intrinsic protein disorder annotation in 2020
- 2020
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
-
Tidskriftsartikel (refereegranskat)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
|
|
| 10. |
- Herbertsson, Lina, et al.
(författare)
-
Bees increase seed set of wild plants while the proportion of arable land has a variable effect on pollination in European agricultural landscapes
- 2021
-
Ingår i: Plant Ecology and Evolution. - : Societe Royale de Botanique de Belgique. - 2032-3913 .- 2032-3921. ; 154:3, s. 341-350
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Agricultural intensification and loss of farmland heterogeneity have contributed to population declines of wild bees and other pollinators, which may have caused subsequent declines in insect-pollinated wild plants.Material and methods: Using data from 37 studies on 22 pollinator-dependent wild plant species across Europe, we investigated whether flower visitation and seed set of insect-pollinated plants decline with an increasing proportion of arable land within 1 km.Key results: Seed set increased with increasing flower visitation by bees, most of which were wild bees, but not with increasing flower visitation by other insects. Increasing proportion of arable land had a strongly variable effect on seed set and flower visitation by bees across studies.Conclusion:Factors such as landscape configuration, local habitat quality, and temporally changing resource availability (e.g. due to mass-flowering crops or honey bee hives) could have modified the effect of arable land on pollination. While our results highlight that the persistence of wild bees is crucial to maintain plant diversity, we also show that pollen limitation due to declining bee populations in homogenized agricultural landscapes is not a universal driver causing parallel losses of bees and insect-pollinated plants.
|
|
