| 1. |
- Muscarella, Robert, et al.
(författare)
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The global abundance of tree palms
- 2020
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 29:9, s. 1495-1514
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Tidskriftsartikel (refereegranskat)abstract
- AimPalms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change.LocationTropical and subtropical moist forests.Time periodCurrent.Major taxa studiedPalms (Arecaceae).MethodsWe assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure.ResultsOn average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work.ConclusionsTree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.
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| 2. |
- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 3. |
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| 4. |
- Church, Deanna M, et al.
(författare)
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Lineage-specific biology revealed by a finished genome assembly of the mouse
- 2009
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:5, s. e1000112-
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Tidskriftsartikel (refereegranskat)abstract
- The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non-protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not.
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| 5. |
- Balkenhol, Maschenka C. A., et al.
(författare)
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Deep learning assisted mitotic counting for breast cancer
- 2019
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Ingår i: Laboratory Investigation. - : NATURE PUBLISHING GROUP. - 0023-6837 .- 1530-0307. ; 99:11, s. 1596-1606
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Tidskriftsartikel (refereegranskat)abstract
- As part of routine histological grading, for every invasive breast cancer the mitotic count is assessed by counting mitoses in the (visually selected) region with the highest proliferative activity. Because this procedure is prone to subjectivity, the present study compares visual mitotic counting with deep learning based automated mitotic counting and fully automated hotspot selection. Two cohorts were used in this study. Cohort A comprised 90 prospectively included tumors which were selected based on the mitotic frequency scores given during routine glass slide diagnostics. This pathologist additionally assessed the mitotic count in these tumors in whole slide images (WSI) within a preselected hotspot. A second observer performed the same procedures on this cohort. The preselected hotspot was generated by a convolutional neural network (CNN) trained to detect all mitotic figures in digitized hematoxylin and eosin (Hamp;E) sections. The second cohort comprised a multicenter, retrospective TNBC cohort (n = 298), of which the mitotic count was assessed by three independent observers on glass slides. The same CNN was applied on this cohort and the absolute number of mitotic figures in the hotspot was compared to the averaged mitotic count of the observers. Baseline interobserver agreement for glass slide assessment in cohort A was good (kappa 0.689; 95% CI 0.580-0.799). Using the CNN generated hotspot in WSI, the agreement score increased to 0.814 (95% CI 0.719-0.909). Automated counting by the CNN in comparison with observers counting in the predefined hotspot region yielded an average kappa of 0.724. We conclude that manual mitotic counting is not affected by assessment modality (glass slides, WSI) and that counting mitotic figures in WSI is feasible. Using a predefined hotspot area considerably improves reproducibility. Also, fully automated assessment of mitotic score appears to be feasible without introducing additional bias or variability.
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| 6. |
- Balkenhol, Maschenka C. A., et al.
(författare)
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Histological subtypes in triple negative breast cancer are associated with specific information on survival
- 2020
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Ingår i: Annals of Diagnostic Pathology. - : ELSEVIER SCIENCE INC. - 1092-9134 .- 1532-8198. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC. A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed. Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18-3.03; p = 0.008; OS HR 1.94; 95% CI 1.28-2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes. In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.
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| 7. |
- Balkenhol, Maschenka C. A., et al.
(författare)
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Optimized tumour infiltrating lymphocyte assessment for triple negative breast cancer prognostics
- 2021
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Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 56, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- The tumour microenvironment has been shown to be a valuable source of prognostic information for different cancer types. This holds in particular for triple negative breast cancer (TNBC), a breast cancer subtype for which currently no prognostic biomarkers are established. Although different methods to assess tumour infiltrating lymphocytes (TILs) have been published, it remains unclear which method (marker, region) yields the most optimal prognostic information. In addition, to date, no objective TILs assessment methods are available. For this proof of concept study, a subset of our previously described TNBC cohort (n = 94) was stained for CD3, CD8 and FOXP3 using multiplex immunohistochemistry and subsequently imaged by a multispectral imaging system. Advanced whole-slide image analysis algorithms, including convolutional neural networks (CNN) were used to register unmixed multispectral images and corresponding H&E sections, to segment the different tissue compartments (tumour, stroma) and to detect all individual positive lymphocytes. Densities of positive lymphocytes were analysed in different regions within the tumour and its neighbouring environment and correlated to relapse free survival (RFS) and overall survival (OS). We found that for all TILs markers the presence of a high density of positive cells correlated with an improved survival. None of the TILs markers was superior to the others. The results of TILs assessment in the various regions did not show marked differences between each other. The negative correlation between TILs and survival in our cohort are in line with previous studies. Our results provide directions for optimizing TILs assessment methodology. (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 8. |
- Fairfield, Heather, et al.
(författare)
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Mutation discovery in mice by whole exome sequencing
- 2011
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 12:9, s. R86-
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Tidskriftsartikel (refereegranskat)abstract
- We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.
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| 9. |
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| 10. |
- Severson, Tesa M., et al.
(författare)
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Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer (MBC) is rare and largely hormonally driven. Here, the authors examine the action of steroid hormone receptors in male and female breast cancers and find gender selective hormone receptor action that associates with the survival of MBC patients.
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