| 1. |
|
|
| 2. |
- Bedoya-Reina, O. C., et al.
(author)
-
Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome. Childhood neuroblastoma can be separated into high and low risk groups, with prognosis depending on age at diagnosis. Here, the authors show that low and high risk neuroblastoma tumours are composed of different cell types with different malignancy potential.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Christofer Juhlin, C., et al.
(author)
-
Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene
- 2015
-
In: Genes, Chromosomes and Cancer. - : Wiley: 12 months. - 1045-2257 .- 1098-2264. ; 54:9, s. 542-554
-
Journal article (peer-reviewed)abstract
- As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Ask, Maria, et al.
(author)
-
The Innovative Exploration Drilling and Data Acquisition Research School
- 2021
-
In: NSG2021 27th European Meeting of Environmental and Engineering Geophysics. - : European Association of Geoscientists and Engineers.
-
Conference paper (peer-reviewed)abstract
- The Innovative Exploration Drilling and Data Acquisition Research School (I-EDDA-RS) is aimed at educating emerging scientists and engineers in on-site drilling and geoscientific investigation technology for mining. I-EDDA-RS consists if a consortium of scientists and specialists from six universities and research institutes in Germany and Sweden. A central component of the research school is that the courses have hands-on components at drill sites, boreholes and repositories. In addition, a course on entrepreneurial skills required in the exploration industry is also included in I-EDDA-RS. The arrival of the Covid-19 pandemic resulted in altered plans. Instead of offering ten courses with strong field work, practical, and entrepreneurial components during 2020, four courses via distant learning were offered. While this was disappointing in many aspects, two of the courses attracted a larger group of students from a wider part of the world than original envisioned. Outreach via on-line and open webinars is also a route to explore, as a complement to meetings and conferences in real life. The I-EDDA-RS courses in 2021 welcomes students at MSc & PhD level, as well as experienced professionals for lifelong learning (c.f. https://www.iedda.eu/rs). The form and type of teaching is to be determined.
|
|
| 10. |
- Carlsson, Axel C, et al.
(author)
-
Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes : findings from two community based cohorts of elderly
- 2014
-
In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 237:1, s. 236-242
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Giese, R., et al.
(author)
-
Monitoring at the CO2SINK Site : A Concept Integrating Geophysics, Geochemistry and Microbiology
- 2009
-
In: Proceedings of the 9th International Conference on Greenhouse Gas Control Technologies (GHGT-9), 16–20 November 2008, Washington DC, USAGREENHOUSE GAS CONTROL TECHNOLOGIES 9. - : Elsevier BV. ; , s. 2251-2259
-
Conference paper (other academic/artistic)abstract
- At the CO2SINK site (Ketzin, near Berlin, Germany), the pilot study for onshore CO2 storage in saline aquifers includes monitoring of the storage reservoir and the structures above using physical, chemical, and microbial observations. Seismic and geoelectric measurements have delivered the structural framework and monitor CO2 propagation between two observation wells. Borehole temperature data serves to derive information about in-situ formation temperatures and to detect processes related to the injection and movement of CO2 in the subsurface. Pressure measurements aim at ensuring safe operations and characterization of the reservoir. For a complete characterization of the CO2 storage process, the physical observations have to be complemented by chemical and biological probing, as fluid/fluid and fluid/rock interactions and microbial processes play an important role possibly affecting the stability of the reservoir and caprock. A newly developed Gas Membrane Sensor detected the CO2 breakthrough on the first monitoring well. Microbial investigations contributed in optimizing the injection borehole after recognizing organisms reducing its injectivity.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Juhlin, C., et al.
(author)
-
Crustal reflectivity near the Archean-Proterozoic boundary in northern Sweden and implications for the tectonic evolution of the area
- 2002
-
In: Geophysical Journal International. - 0956-540X .- 1365-246X. ; 150:1, s. 180-197
-
Journal article (peer-reviewed)abstract
- Sm–Nd isotope ratios of 1.9–1.8 Ga granitoids delineate the Archaean–Proterozoic boundary in northern Sweden, an important feature in the Fennoscandian Shield. The boundary strikes approximately WNW–ESE and is defined as a c. 20 km wide zone with juvenile Palaeoproterozoic rocks to the SSW and Archaean and Proterozoic rocks, derived to a large extent from Archaean sources, to the NNE. It therefore constitutes the strongly reworked margin of the old Archaean craton. Extrapolation of the boundary offshore into the Bothnian Bay and correlation with the marine reflection seismic BABEL Lines 2 and 3/4 indicates that the boundary dips to the south-southwest, consistent with interpretation of the Sm–Nd data. In order to tie the BABEL results with onshore surface geology and obtain detailed images of the uppermost crust a short (30 km of subsurface coverage) pilot profile was acquired in the Luleå area of northern Sweden during August 1999. The profile consisted of a high-resolution shallow component (1 kg shots) and a lower-resolution deep component (12 kg shots). Both components image most of the reflective crust, with the deep component providing a better image below 10 s. Comparison of signal penetration curves with data acquired over the Trans-Scandinavian Igneous Belt (a large batholith) indicate the transparent nature of the crust there to be caused by geological factors, not acquisition parameters. Lower crustal reflectivity patterns on the Luleå test profile are similar to those observed on the BABEL lines, suggesting the same lower crust onshore as offshore. Interpreted Archaean reflective upper crust in the NE extends below more transparent Proterozoic crust in the SW. This transparent crust contains a number of high-amplitude reflectors that may represent shear zones and/or mafic rock within granite intrusions. A marked boundary in the magnetic field in the SW has been interpreted as being the result of a gently west-dipping contact zone between meta-sediments and felsic volcanic rocks, however, the seismic data indicate a near-vertical structure in this area. By correlating the onshore and offshore seismic data we have better defined the location of the Archaean–Proterozoic boundary on the BABEL profiles. Our new interpretation of the crustal structure along the northern part of the BABEL Line 2 shows a more bi-vergent geometry than previous interpretations. Comparison of the re-interpreted crustal structure in northern Sweden with that found in the Middle Urals shows several similarities, in particular the accretion of a series of arcs to a stable craton. Based on this similarity and geological data, we deduce that a continental arc accreted to the southwestern margin of the Archaean craton at c. 1.87 Ga. Shortly thereafter, the Skellefte island arc underthrust the continental arc owing to a collision further to the southwest resulting in the bi-vergent crustal structure observed today.
|
|
| 20. |
|
|
| 21. |
- Juhlin, C, et al.
(author)
-
Loss of parafibromin expression in a subset of parathyroid adenomas
- 2006
-
In: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 13:2, s. 509-523
-
Journal article (peer-reviewed)abstract
- Inactivation of the hyperparathyroidism–jaw tumour syndrome (HPT– JT) gene, HRPT2, was recently established as a genetic mechanism in the development of parathyroid tumours. Its encoded protein parafibromin has tumour-suppressor properties that play an important role in tumour development in the parathyroids, jaws and kidneys. Inactivating HRPT2 mutations are common in HPT– JT and parathyroid carcinomas, and have been described in a few cases of parathyroid adenomas with cystic features. In this study, 46 cases of cystic parathyroid adenomas previously investigated for HRPT2 mutations were characterized with regard to MEN1 gene mutations, cyclin D1 expression and parafibromin expression. In normal tissues and cell lines, parafibromin was ubiquitously expressed. Furthermore, parafibromin was detected as a dominating nuclear and a weaker cytoplasmic signal in transfected cell lines. In the three parathyroid tumours with inactivating HRPT2 mutations parafibromin expression was not detectable, and in one of two cases with aberrantly sized parafibromin the protein was delocalized. Both high and low cyclin D1 levels were found among HRPT2-mutated and -unmutated tumours, suggesting that these events are not mutually exclusive in parathyroid tumour development. The presented data suggest that in the majority of benign parathyroid tumours the expression of parafibromin remains unaltered, while the loss of parafibromin expression is strongly indicative of gene inactivation through mutation of the HRPT2 gene.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
