| 1. |
- Kaasinen, E, et al.
(författare)
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Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
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Tidskriftsartikel (refereegranskat)abstract
- Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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| 11. |
- Mahlamaki, EH, et al.
(författare)
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Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 35:4, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- Genetic changes involved in the development and progression of pancreatic cancer are still partly unknown, despite the progress in recent years. In this study, comparative genomic hybridization analysis in 31 pancreatic cancer cell lines showed that chromosome arms 8q, 11q, 17q, and 20q are frequently gained in this tumor type. Copy number analysis of selected genes from these chromosome arms by fluorescence in situ hybridization showed amplification of the MYC oncogene in 54% of the cell lines, whereas CCNDI was amplified in 28%. In the 17q arm, the ERB82 oncogene was amplified in 20% of the cell lines, TBX2 in 50%, and BIRC5 in 58%, indicating increased involvement toward the q telonnere of chromosome 17. In the 20q arm, the amplification frequencies varied from 32% to 83%, with the CTSZ gene at 20q 13 being most frequently affected. These results illustrate that amplification of genes from the 8q, 11q, 17q, and 20q chromosome arms is common in pancreatic cancer.
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| 12. |
- Tanner, M M, et al.
(författare)
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Genetic aberrations in hypodiploid breast cancer: frequent loss of chromosome 4 and amplification of cyclin D1 oncogene
- 1998
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Ingår i: American Journal of Pathology. - 1525-2191. ; 153:1, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of somatic genetic aberrations in breast cancer has remained poorly understood. The most common chromosomal abnormality is hyperdiploidy, which is thought to arise via a transient hypodiploid state. However, hypodiploidy persists in 1 to 2% of breast tumors, which are characterized by a poor prognosis. We studied the genetic aberrations in 15 flow cytometrically hypodiploid breast cancers by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). Surprisingly, numerous copy number gains were detected in addition to the copy number losses. The number of gains per tumor was 4.3 +/- 3.2 and that of losses was 4.5 +/- 3.3 (mean +/- SD), which is similar to that previously observed in hyperdiploid breast cancers. Gains at chromosomes or chromosomal regions at 11q13, 1q, 19, and 16p and losses of 2q, 4, 6q, 9p, 13, and 18 were most commonly observed. Compared with unselected breast carcinomas, hypodiploid tumors showed certain differences. Loss of chromosome 4 (53%) and gain of 11q13 (60%) were significantly more common in hypodiploid tumors. The gain at 11q13 was found by FISH to harbor amplification of the Cyclin D1 oncogene, which is therefore three to four times more common in hypodiploid than in unselected breast cancers (15 to 20%). Structural chromosomal aberrations (such as Cyclin D1 amplification) were present both in diploid and hypodiploid tumor cell populations, as assessed by FISH and CGH after flow cytometric sorting. Together these results indicate that hypodiploid tumors form a distinct genetic entity of invasive breast cancer, although they probably share a common genetic evolution pathway where structural chromosomal aberrations precede gross DNA ploidy changes.
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| 13. |
- Tirkkonen, M, et al.
(författare)
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Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations
- 1997
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Ingår i: Cancer Research. - 0008-5472. ; 57:7, s. 7-1222
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers from 21 BRCA1 mutation carriers, 15 BRCA2 mutation carriers, and 55 unselected controls. The total number of genetic changes was almost two times higher in tumors from both BRCA1 and BRCA2 mutation carriers than in the control group. In BRCA1 tumors, losses of 5q (86%), 4q (81%), 4p (64%), 2q (40%), and 12q (40%) were significantly more common than in the control group (7-13%). BRCA2 tumors were characterized by a higher frequency of 13q (73%) and 6q (60%) losses and gains of 17q22-q24 (87%) and 20q13 (60%) as compared to the prevalence of these changes in the control group (12-18%). In conclusion, accumulation of somatic genetic changes during tumor progression may follow a unique pathway in individuals genetically predisposed to cancer, especially by the BRCA1 gene. Activation or loss of genes in the affected chromosomal regions may be selected for during tumor progression in cells lacking functional BRCA1 or BRCA2. Identification of such genes could provide targets for therapeutic intervention and early diagnosis.
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| 16. |
- Clark, R., et al.
(författare)
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Developing a robust self evaluation framework for active learning : The first stage of an ERASMUS+ project (QAEMarketPlace4HEI)
- 2015
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Ingår i: Proceedings of the 43rd SEFI Annual Conference 2015 - Diversity in Engineering Education: An Opportunity to Face the New Trends of Engineering, SEFI 2015. - : European Society for Engineering Education (SEFI). - 9782873520120
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Konferensbidrag (refereegranskat)abstract
- In ensuring the quality of learning and teaching in Higher Education, self-evaluation is an important component of the process. An example would be the approach taken within the CDIO community whereby self-evaluation against the CDIO standards is part of the quality assurance process. Eight European universities (Reykjavik University, Iceland; Turku University of Applied Sciences, Finland; Aarhus University, Denmark; Helsinki Metropolia University of Applied Sciences, Finland; Umeå University, Sweden; Telecom Bretagne, France; Aston University, United Kingdom; Queens University Belfast, United Kingdom) are engaged in an EU funded Erasmus + project that is exploring the quality assurance process associated with active learning.
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| 17. |
- Dunlop, Malcolm G, et al.
(författare)
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Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
- 2012
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
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| 18. |
- Georgitsi, Marianthi, et al.
(författare)
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Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia.
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:8, s. 3321-5
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Germline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two acromegalic patients.OBJECTIVE: Our objective was to evaluate the role of CDKN1B/p27(Kip1) in human tumor predisposition in patients clinically suspected of MEN1 but testing negative for MEN1 germline mutation as well as in familial and sporadic acromegaly/pituitary adenoma patients.DESIGN: Genomic DNA was analyzed for germline mutations in the CDKN1B/p27(Kip1) gene by PCR amplification and direct sequencing.SETTING: The study was conducted at nonprofit academic research and medical centers.PATIENTS: Thirty-six Dutch and one German suspected MEN1 patient, who previously tested negative for germline MEN1 gene mutations, were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary adenoma patients from Europe and the United States were included in the study.MAIN OUTCOME MEASURES: We analyzed germline CDKN1B/p27(Kip1) mutations in individuals with pituitary adenoma and MEN1-like features.RESULTS: A heterozygous 19-bp duplication (c.59_77dup19) leading to a truncated protein product was identified in one Dutch patient with suspected MEN1 phenotype, pituitary adenoma, carcinoid tumor, and hyperparathyroidism (one of 36, 2.8%). No mutations were detected in either familial or sporadic acromegaly/pituitary adenoma patients.CONCLUSIONS: Our results support the previous finding that germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition. However, such mutations appear uncommon in suspected MEN1 cases and rare or nonexistent in familial or sporadic acromegaly/pituitary adenoma patients.
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| 20. |
- Heinonen, HR, et al.
(författare)
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Global metabolomic profiling of uterine leiomyomas
- 2017
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 117:12, s. 1855-1864
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Tidskriftsartikel (refereegranskat)
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| 21. |
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| 22. |
- Kainu, T, et al.
(författare)
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Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus
- 2000
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 97:17, s. 9603-9608
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.
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| 23. |
- Kotilainen, Aarno T., et al.
(författare)
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Echoes from the Past : A Healthy Baltic Sea Requires More Effort
- 2014
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 43:1, s. 60-68
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Tidskriftsartikel (refereegranskat)abstract
- Integrated sediment multiproxy studies and modeling were used to reconstruct past changes in the Baltic Sea ecosystem. Results of natural changes over the past 6000 years in the Baltic Sea ecosystem suggest that forecasted climate warming might enhance environmental problems of the Baltic Sea. Integrated modeling and sediment proxy studies reveal increased sea surface temperatures and expanded seafloor anoxia (in deep basins) during earlier natural warm climate phases, such as the Medieval Climate Anomaly. Under future IPCC scenarios of global warming, there is likely no improvement of bottom water conditions in the Baltic Sea. Thus, the measures already designed to produce a healthier Baltic Sea are insufficient in the long term. The interactions between climate change and anthropogenic impacts on the Baltic Sea should be considered in management, implementation of policy strategies in the Baltic Sea environmental issues, and adaptation to future climate change.
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| 25. |
- Polyakov, S. M., et al.
(författare)
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Nonlinear optical response and structural properties of MBE-grown Fe:ZnS films
- 2018
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Ingår i: Optical Materials Express. - : Optical Society of America. - 2159-3930. ; 8:2, s. 356-367
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Tidskriftsartikel (refereegranskat)abstract
- Fe-doped ZnS films of high optical quality were fabricated using vacuum vapor deposition. Preferential crystalline orientation and phase purity of the host ZnS films were increased by the addition of small amounts of Fe, and the spectral shape of the 2-4 μm absorption peak is maintained up to the highest concentration tested (9 at.%). However, Raman shifts of the Fe:ZnS films indicate the inclusion of disordered material at high Fe concentrations, and below-gap optical Kerr effect measurements show an increase in χ(3) correlated with this data. Nonlinear optical properties of the films were also measured using the Z-scan method at 532 nm, and saturable absorption of the Fe-based intraband levels at 2.94 μm was confirmed.
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| 26. |
- Roslin, Tomas, et al.
(författare)
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A molecular-based identification resource for the arthropods of Finland
- 2022
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 22:2, s. 803-822
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Tidskriftsartikel (refereegranskat)abstract
- To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.
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| 27. |
- Spindlberger, L., et al.
(författare)
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Optical Properties of Vanadium in 4H Silicon Carbide for Quantum Technology
- 2019
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Ingår i: Physical Review Applied. - : AMER PHYSICAL SOC. - 2331-7019. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- We study the optical properties of tetravalent-vanadium impurities in 4H silicon carbide. Light emission from two crystalline sites is observed at wavelengths of 1.28 and 1.33 mu m, with optical lifetimes of 163 and 43 ns, respectively, which remains stable up to 50 and 20 K, respectively. Moreover, spectrally broad photoluminescence is observed up to room temperature. Group-theory and ab initio density-functional supercell calculations enable unequivocal site assignment and shed light on the spectral features of the defects. Specifically, our numerical simulations indicate that the site assignment is reversed with respect to previous assumptions. Our calculations show that vanadium in silicon carbide has highly favorable properties for the generation of single photons in the telecommunication wavelength regime. Combined with the available electronic and nuclear degrees of freedom, vanadium presents all the ingredients required for a highly efficient spin-photon interface.
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| 28. |
- Tolstik, Nikolai, et al.
(författare)
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Spectral-luminescent properties of vapor deposited Cr:ZnS thin films and their application as saturable absorbers for 1.5-mu m erbium lasers
- 2018
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Ingår i: Optical Materials Express. - : Optical Society of America. - 2159-3930. ; 8:3, s. 522-531
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of the extensive spectral-luminescent characterization including concentration quenching analysis of the first laser-quality vapor-deposited Cr:ZnS films, and demonstrate their use as saturable absorbers. Comparison of spectral-luminescent properties with bulk Cr: ZnS indicates their high laser quality, opening the way towards industrial mid-IR thin-disk and waveguide lasers. Successful implementation of the grown films in a Q-switched Er, Yb:GdAB solid-state laser emitting at 1.52 mu m gives clear experimental evidence of the high quality of the films.
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