| 1. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 3. |
- Eeraerts, Maxime, et al.
(författare)
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Pollination deficits and their relation with insect pollinator visitation are cultivar-dependent in an entomophilous crop
- 2024
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Ingår i: Agriculture, Ecosystems and Environment. - 0167-8809. ; 369
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Tidskriftsartikel (refereegranskat)abstract
- Insects contribute considerably to global crop pollination, with pollination deficits being documented for multiple entomophilous or pollinator-dependent crops. Different cultivars of crops are being cultivated within and across production regions, so it is essential to understand the cultivar variability of pollination deficits. Here, we used a dataset from 286 sites from multiple production regions to develop a synthesis on pollination deficits in two widely cultivated highbush blueberry cultivars, ‘Bluecrop’ and ‘Duke’. Additionally, we determined if bee visitation or bee richness reduces pollination deficits in these cultivars. On average, neither cultivar showed pollination deficits regarding fruit set. However, for ‘Bluecrop’ we found pollination deficits for berry weight and seed set, which was not the case for ‘Duke’. Increasing total bee visitation reduced pollination deficits of both berry weight and seed set for ‘Bluecrop’. More specifically, a non-linear, negative exponential model best predicted this relation between bee visitation and pollination deficits. Our results highlight that pollination deficits and responses to pollinator visitation are variable between different cultivars of a single crop, which suggests opportunities to use certain cultivars that are less dependent on insect-mediated pollination in landscapes and regions where pollination services have been compromised. In addition, the non-linear response between bee visitation and pollination deficits suggests that optimal bee visitation rates need to be determined to improve pollination management and crop yield and to support accurate economic valuations of pollination services.
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| 4. |
- Eeraerts, Maxime, et al.
(författare)
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Synthesis of highbush blueberry pollination research reveals region-specific differences in the contributions of honeybees and wild bees
- 2023
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Ingår i: Journal of Applied Ecology. - 0021-8901. ; 60:12, s. 2528-2539
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Forskningsöversikt (refereegranskat)abstract
- Highbush blueberry production has expanded worldwide in recent decades. To safeguard future yields, it is essential to understand if insect pollination is limiting current blueberry production and which insects contribute to pollination in different production regions. We present a systematic review including a set of meta-analyses on insect-mediated pollination in highbush blueberry. We summarize the geographic distribution of research, the abundance of different pollinator taxa and their relative pollination contributions. Using raw data from 21 studies, totalling 496 site replicates, we determine the degree of pollination service and pollen limitation (i.e. combining open pollination levels with experimental bagged and/or hand pollination treatments), as well as the contribution of honeybees and wild bees to pollination (i.e. observational, open pollination). Most studies originate from North America, focusing on only a few cultivars. Honeybees are the dominant pollinator, and wild bees are occasionally abundant. Wild bees are more efficient pollinators on a single-visit basis compared to honeybees, which increases their relative pollination contribution compared to their relative abundance. Insect-mediated pollination services increased blueberry fruit set, berry weight and seed set (R2 values: 64.8%, 75.9% and 75.2% respectively). We often detected pollen limitation, indicated by an increase in fruit set, berry weight and seed set (R2: 10.1%, 18.2% and 21.5%, respectively), with additional hand pollination. Increasing visitation of honeybees and wild bees contributed to blueberry pollination by increasing fruit set (R2: 5.4% and 3.5%), berry weight (R2: 6.5% and 2.8%) and seed set (R2: 6.4% and 3.8%) respectively. Bee contributions to fruit set and berry weight were variable across regions. Synthesis and application: A diverse community of insects, primarily bees, contributes to highbush blueberry pollination and yield. However, pollination deficits are common. The finding that both honeybees and wild bees enhance pollination highlights the possibility of adopting different management strategies that utilize honeybees, wild bees or both depending on the specific context and region. This further emphasizes the general importance of conserving pollinator health and diversity. Our synthesis highlights data gaps and areas for future research to better understand the pollination contribution of different pollinators to crops that are expanding globally.
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| 5. |
- Lindemann, Kristina, et al.
(författare)
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Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist)
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:4, s. 455-463
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Methods: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Results: Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P = 0.003). There was no difference in OS between the treatment arms. Conclusions: Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.
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