| 1. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 2. |
- Morrison, C. A., et al.
(författare)
-
Bird population declines and species turnover are changing the acoustic properties of spring soundscapes
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Natural sounds, and bird song in particular, play a key role in building and maintaining our connection with nature, but widespread declines in bird populations mean that the acoustic properties of natural soundscapes may be changing. Using data-driven reconstructions of soundscapes in lieu of historical recordings, here we quantify changes in soundscape characteristics at more than 200,000 sites across North America and Europe. We integrate citizen science bird monitoring data with recordings of individual species to reveal a pervasive loss of acoustic diversity and intensity of soundscapes across both continents over the past 25 years, driven by changes in species richness and abundance. These results suggest that one of the fundamental pathways through which humans engage with nature is in chronic decline, with potentially widespread implications for human health and well-being.
|
|
| 3. |
- Pellissier, V., et al.
(författare)
-
Effects of Natura 2000 on nontarget bird and butterfly species based on citizen science data
- 2020
-
Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 34:3, s. 666-676
-
Tidskriftsartikel (refereegranskat)abstract
- The European Union's Natura 2000 (N2000) is among the largest international networks of protected areas. One of its aims is to secure the status of a predetermined set of (targeted) bird and butterfly species. However, nontarget species may also benefit from N2000. We evaluated how the terrestrial component of this network affects the abundance of nontargeted, more common bird and butterfly species based on data from long-term volunteer-based monitoring programs in 9602 sites for birds and 2001 sites for butterflies. In almost half of the 155 bird species assessed, and particularly among woodland specialists, abundance increased (slope estimates ranged from 0.101 [SD 0.042] to 3.51 [SD 1.30]) as the proportion of landscape covered by N2000 sites increased. This positive relationship existed for 27 of the 104 butterfly species (estimates ranged from 0.382 [SD 0.163] to 4.28 [SD 0.768]), although most butterflies were generalists. For most species, when land-cover covariates were accounted for these positive relationships were not evident, meaning land cover may be a determinant of positive effects of the N2000 network. The increase in abundance as N2000 coverage increased correlated with the specialization index for birds, but not for butterflies. Although the N2000 network supports high abundance of a large spectrum of species, the low number of specialist butterflies with a positive association with the N2000 network shows the need to improve the habitat quality of N2000 sites that could harbor open-land butterfly specialists. For a better understanding of the processes involved, we advocate for standardized collection of data at N2000 sites.
|
|
| 4. |
- Chang, H., et al.
(författare)
-
The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
- 2018
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:2, s. 400-412
-
Tidskriftsartikel (refereegranskat)abstract
- Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
|
|
| 5. |
- Morrison, Catriona A., et al.
(författare)
-
Covariation in population trends and demography reveals targets for conservation action
- 2021
-
Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 288:1946, s. 20202955-20202955
-
Tidskriftsartikel (refereegranskat)abstract
- Wildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified. Targeted actions to improve conditions on poor-quality sites could be an effective approach, but only if local conditions consistently influence local demography and hence population trends. Using long-term measures of abundance and demography of breeding birds at survey sites across Europe, we show that co-occurring species with differing migration behaviours have similar directions of local population trends and magnitudes of productivity, but not survival rates. Targeted actions to boost local productivity within Europe, alongside large-scale (non-targeted) environmental protection across non-breeding ranges, could therefore help address the urgent need to halt migrant landbird declines. Such demographic routes to recovery are likely to be increasingly needed to address global wildlife declines.
|
|
| 6. |
- Stephens, Philip A., et al.
(författare)
-
Consistent response of bird populations to climate change on two continents
- 2016
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6281, s. 84-87
-
Tidskriftsartikel (refereegranskat)abstract
- Global climate change is a major threat to biodiversity. Large-scale analyses have generally focused on the impacts of climate change on the geographic ranges of species and on phenology, the timing of ecological phenomena. We used long-term monitoring of the abundance of breeding birds across Europe and the United States to produce, for both regions, composite population indices for two groups of species: those for which climate suitability has been either improving or declining since 1980. The ratio of these composite indices, the climate impact indicator (CII), reflects the divergent fates of species favored or disadvantaged by climate change. The trend in CII is positive and similar in the two regions. On both continents, interspecific and spatial variation in population abundance trends are well predicted by climate suitability trends.
|
|
| 7. |
- Lombardo, S., et al.
(författare)
-
SCALA : In situ calibration for integral field spectrographs
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 607
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. The scientific yield of current and future optical surveys is increasingly limited by systematic uncertainties in the flux calibration. This is the case for type Ia supernova (SN Ia) cosmology programs, where an improved calibration directly translates into improved cosmological constraints. Current methodology rests on models of stars. Here we aim to obtain flux calibration that is traceable to state-of-the-art detector-based calibration. Methods. We present the SNIFS Calibration Apparatus (SCALA), a color (relative) flux calibration system developed for the SuperNova integral field spectrograph (SNIFS), operating at the University of Hawaii 2.2 m (UH 88) telescope. Results. By comparing the color trend of the illumination generated by SCALA during two commissioning runs, and to previous laboratory measurements, we show that we can determine the light emitted by SCALA with a long-term repeatability better than 1%. We describe the calibration procedure necessary to control for system aging. We present measurements of the SNIFS throughput as estimated by SCALA observations. Conclusions. The SCALA calibration unit is now fully deployed at the UH 88 telescope, and with it color-calibration between 4000 angstrom and 9000 angstrom is stable at the percent level over a one-year baseline.
|
|
| 8. |
- Mason, Lucy R., et al.
(författare)
-
Population responses of bird populations to climate change on two continents vary with species’ ecological traits but not with direction of change in climate suitability
- 2019
-
Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 157:3-4, s. 337-354
-
Tidskriftsartikel (refereegranskat)abstract
- Climate change is a major global threat to biodiversity with widespread impacts on ecological communities. Evidence for beneficial impacts on populations is perceived to be stronger and more plentiful than that for negative impacts, but few studies have investigated this apparent disparity, or how ecological factors affect population responses to climatic change. We examined the strength of the relationship between species-specific regional population changes and climate suitability trends (CST), using 30-year datasets of population change for 525 breeding bird species in Europe and the USA. These data indicate a consistent positive relationship between population trend and CST across the two continents. Importantly, we found no evidence that this positive relationship differs between species expected to be negatively and positively impacted across the entire taxonomic group, suggesting that climate change is causing equally strong, quantifiable population increases and declines. Species’ responses to changing climatic suitability varied with ecological traits, however, particularly breeding habitat preference and body mass. Species associated with inland wetlands responded most strongly and consistently to recent climatic change. In Europe, smaller species also appeared to respond more strongly, whilst the relationship with body mass was less clear-cut for North American birds. Overall, our results identify the role of certain traits in modulating responses to climate change and emphasise the importance of long-term data on abundance for detecting large-scale species’ responses to environmental changes.
|
|
| 9. |
- Gamero, Anna, et al.
(författare)
-
Tracking Progress Toward EU Biodiversity Strategy Targets : EU Policy Effects in Preserving its Common Farmland Birds
- 2017
-
Ingår i: Conservation Letters. - : Wiley. - 1755-263X. ; 10:4, s. 395-402
-
Tidskriftsartikel (refereegranskat)abstract
- Maximizing the area under biodiversity-related conservation measures is a main target of the European Union (EU) Biodiversity Strategy to 2020. We analyzed whether agrienvironmental schemes (AES) within EU common agricultural policy, special protected areas for birds (SPAs), and Annex I designation within EU Birds Directive had an effect on bird population changes using monitoring data from 39 farmland bird species from 1981 to 2012 at EU scale. Populations of resident and short-distance migrants were larger with increasing SPAs and AES coverage, while Annex I species had higher population growth rates with increasing SPAs, indicating that SPAs may contribute to the protection of mainly target species and species spending most of their life cycle in the EU. Because farmland birds are in decline and the negative relationship of agricultural intensification with their population growth rates was evident during the implementation of AES and SPAs, EU policies seem to generally attenuate the declines of farmland bird populations, but not to reverse them.
|
|
| 10. |
- Schlebusch, Stephen A., et al.
(författare)
-
Rapid gene content turnover on the germline-restricted chromosome in songbirds
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Songbirds have an extra chromosome with unknown function found only in their germline. This study assembles and compares this chromosome in two closely related nightingale species, finding large differences in genetic content and only one conserved gene with probable essential function. The germline-restricted chromosome (GRC) of songbirds represents a taxonomically widespread example of programmed DNA elimination. Despite its apparent indispensability, we still know very little about the GRC's genetic composition, function, and evolutionary significance. Here we assemble the GRC in two closely related species, the common and thrush nightingale. In total we identify 192 genes across the two GRCs, with many of them present in multiple copies. Interestingly, the GRC appears to be under little selective pressure, with the genetic content differing dramatically between the two species and many GRC genes appearing to be pseudogenized fragments. Only one gene, cpeb1, has a complete coding region in all examined individuals of the two species and shows no copy number variation. The acquisition of this gene by the GRC corresponds with the earliest estimates of the GRC origin, making it a good candidate for the functional indispensability of the GRC in songbirds.
|
|
