| 1. |
- Kennedy, S. A., et al.
(författare)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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| 2. |
- Markovic, N., et al.
(författare)
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Severe traumatic lesions in the Late Neolithic cattle from the site of At-Vrsac, Serbia
- 2022
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Ingår i: International Journal of Osteoarchaeology. - : Wiley. - 1047-482X .- 1099-1212. ; 32:6, s. 1285-1294
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Tidskriftsartikel (refereegranskat)abstract
- This paper aims to assess the etiology and differential diagnosis of severe pathological lesions in wild and domestic cattle from the Late Neolithic site of At-Vrsac in the northeast part of the present-day Serbia. Excavations of this multilayered site revealed the remains of a Late Neolithic settlement belonging to the Vinca culture network of the Central Balkans. An aurochs metacarpal bone, two domestic cattle fragments of fused ulna and radius and of tibia, all with massive bone proliferations were recovered during the archaeological excavations in 1976. Paleopathological study was undertaken using an interdisciplinary approach, including AMS dating, radiography, computed tomography (CT), and histopathology. The results show severe oblique healed fracture with secondary pronounced bone reaction in the aurochs metacarpal bone and in the domestic cattle ulna-radius, while traumatic alteration infected with disseminated osteomyelitis was found in the domestic cattle tibia. These pathologies of wild and domestic cattle are discussed to reveal the level of environmental and human influence on the origin and development of the lesions in the Late Neolithic cattle.
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| 4. |
- Andjelkov, N., et al.
(författare)
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The enhancement of cartilage regeneration by use of a chitosan-based scaffold in a 3D model of microfracture in vitro : a pilot evaluation
- 2021
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Ingår i: Journal of experimental orthopaedics. - : Springer. - 2197-1153. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Even though various types of scaffolds have been used lately as a complement to microfracture, the exact mechanism of reported cartilage repair improvement when using scaffolds is still unclear. In this study, an effort has been made to identify the specific effects that scaffolds may have on the cells of reparation when using this technique.Methods: A 3‑D model in vitro, representing microfracture and containing both chondrocytes and bone marrow‑derived cells in different experimental conditions was made, and the cells were cultured for eight weeks. Subse‑quently, the constructs containing our 3‑D model were removed from the cell culture medium, fixed in paraffin and analyzed with immunohistochemistry.Results: Bone marrow – derived cells migrated to the upper compartment of the construct through a perforated nylon membrane containing both enzymatically digested‑ and non‑digested particulated cartilage. The histological sections were stained with hematoxylin, eosin, S‑100, SOX‑9, Gomori, and procollagen type I and II. When minced cartilage wasn’t pretreated with collagenase, exclusively bone‑derived cells have created new extracellular matrix as showed by the histological analysis.Conclusions: In this model of microfracture, bone‑derived cells but not chondrocytes have shown to have an active role in new cartilage formation without predigestion with collagenase. Moreover, it seems that the addition of a chitosan‑based scaffold may lead to the improvement of a new cartilage matrix synthesis and integration. This effect hasn’t been seen without the use of scaffold or when a fibrin‑ or a collagen‑based scaffold have been used.
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| 5. |
- Donis, Daphne, et al.
(författare)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Tidskriftsartikel (refereegranskat)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 8. |
- Peña-Pérez, L., et al.
(författare)
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Linked-read whole-genome sequencing resolves common and private structural variants in multiple myeloma
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:17, s. 5009-5023
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is an incurable and aggressive plasma cell malignancy characterized by a complex karyotype with multiple structural variants (SVs) and copy-number variations (CNVs). Linked-read whole-genome sequencing (lrWGS) allows for refined detection and reconstruction of SVs by providing long-range genetic information from standard short-read sequencing. This makes lrWGS an attractive solution for capturing the full genomic complexity of MM. Here we show that high-quality lrWGS data can be generated from low numbers of cells subjected to fluorescence-activated cell sorting (FACS) without DNA purification. Using this protocol, we analyzed MM cells after FACS from 37 patients with MM using lrWGS. We found high concordance between lrWGS and fluorescence in situ hybridization (FISH) for the detection of recurrent translocations and CNVs. Outside of the regions investigated by FISH, we identified .150 additional SVs and CNVs across the cohort. Analysis of the lrWGS data allowed for resolution of the structure of diverse SVs affecting the MYC and t(11;14) loci, causing the duplication of genes and gene regulatory elements. In addition, we identified private SVs causing the dysregulation of genes recurrently involved in translocations with the IGH locus and show that these can alter the molecular classification of MM. Overall, we conclude that lrWGS allows for the detection of aberrations critical for MM prognostics and provides a feasible route for providing comprehensive genetics. Implementing lrWGS could provide more accurate clinical prognostics, facilitate genomic medicine initiatives, and greatly improve the stratification of patients included in clinical trials.
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