1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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2. |
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3. |
- Gerstung, M, et al.
(författare)
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The evolutionary history of 2,658 cancers
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 122-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
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4. |
- Caretta, Martina Angela, et al.
(författare)
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Water
- 2022
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Ingår i: Climate Change 2022: Impacts, Adaptation and Vulnerability : Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change - Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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5. |
- Mantzouki, Evanthia, et al.
(författare)
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Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
- 2018
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Ingår i: Toxins. - : MDPI. - 2072-6651. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
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7. |
- Söderberg, Charlotta, et al.
(författare)
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Options for governance,institutional arrangements andprivate and public decision-making across scales and sectors
- 2018
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Ingår i: Biodiversity and ecosystem services in Nordic coastal ecosystems. - Copenhagen : Nordisk Ministerråd. - 9789289356640 - 9789289356657 ; , s. 161-189
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This report describes the status and trends of biodiversity and ecosystem services in the Nordic region, the drivers and pressures affecting them, interactions and effects on people and society, and options for governance. The main report consists of two volumes. Volume 1 The general overview (this report) and Volume 2 The geographical case studies. This study has been inspired by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystems Services (IPBES). It departs from case studies (Volume 2, the geographical case studies) from ten geographical areas in the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) and the autonomous areas of Faroe Islands, Greenland, and Åland. The aim was to describe status and trends of biodiversity and ecosystem services in the Nordic region, including the drivers and pressures affecting these ecosystems, the effects on people and society and options for governance. The Nordic study is structured as closely as possible to the framework for the regional assessments currently being finalized within IPBES. The report highlights environmental differences and similarities in the Nordic coastal areas, like the inhabitants´ relation to nature and the environment as well as similarities in social and policy instruments between the Nordic countries. This study provides background material for decision-making and it is shown that Nordic cooperation is of great importance for sustainable coastal management and should be strengthened in future work.
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8. |
- Bonebrake, Timothy C., et al.
(författare)
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Managing consequences of climate-driven species redistribution requires integration of ecology, conservation and social science
- 2018
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Ingår i: Biological Reviews. - : Wiley-Blackwell Publishing Inc.. - 1464-7931 .- 1469-185X. ; 93:1, s. 284-305
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Forskningsöversikt (refereegranskat)abstract
- Climate change is driving a pervasive global redistribution of the planet's species. Species redistribution poses new questions for the study of ecosystems, conservation science and human societies that require a coordinated and integrated approach. Here we review recent progress, key gaps and strategic directions in this nascent research area, emphasising emerging themes in species redistribution biology, the importance of understanding underlying drivers and the need to anticipate novel outcomes of changes in species ranges. We highlight that species redistribution has manifest implications across multiple temporal and spatial scales and from genes to ecosystems. Understanding range shifts from ecological, physiological, genetic and biogeographical perspectives is essential for informing changing paradigms in conservation science and for designing conservation strategies that incorporate changing population connectivity and advance adaptation to climate change. Species redistributions present challenges for human well-being, environmental management and sustainable development. By synthesising recent approaches, theories and tools, our review establishes an interdisciplinary foundation for the development of future research on species redistribution. Specifically, we demonstrate how ecological, conservation and social research on species redistribution can best be achieved by working across disciplinary boundaries to develop and implement solutions to climate change challenges. Future studies should therefore integrate existing and complementary scientific frameworks while incorporating social science and human-centred approaches. Finally, we emphasise that the best science will not be useful unless more scientists engage with managers, policy makers and the public to develop responsible and socially acceptable options for the global challenges arising from species redistributions.
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9. |
- 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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10. |
- Mattsson, Lars-Åke, 1945, et al.
(författare)
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Efficacy and tolerability of continuous combined hormone replacement therapy in early postmenopausal women
- 2007
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Ingår i: Menopause Int. ; 13:3, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Continuous combined hormone replacement therapy (ccHRT) based on estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) is effective for relief of menopausal symptoms three years or more after the menopause. This study was undertaken to examine the efficacy and tolerability of ccHRT in early postmenopausal women (last menstrual period 1.3 years before study entry). STUDY DESIGN: This was a 52-week, randomized, double-blind, multinational study of ccHRT comprising three different dose combinations of E(2)V/MPA in 459 early postmenopausal non-hysterectomized women experiencing 30 or more moderate to severe hot flushes a week and/or vasomotor symptoms requiring treatment. MAIN OUTCOMES MEASURES: The primary endpoint was change in frequency and severity of moderate to severe hot flushes at 12 weeks. Secondary outcome measures included number of bleeding days and evaluation of tolerability. RESULTS: The frequency of hot flushes was reduced by >/=70% after one month (P<0.001 for all doses at week 2 onwards), with little evidence of statistically different dose effects. Severity of flushing was also attenuated by ccHRT. Mean number of bleeding days fell to <1 per 28-day cycle at 52 weeks. Rates of amenorrhoea approached 80-90% at the end of the study, but were significantly lower at several time points with the highest-dose regimen (2 mg E(2)V + 5 mg MPA) than with the lower-dose options (1 mg E(2)V + 2.5 mg MPA and 1 mg E(2)V + 5 mg MPA; P<0.05). Adverse events declined in frequency over time with all regimens but throughout the study were more numerous with the highest-dose regimen than with lower doses (P= 0.0002). CONCLUSIONS: Continuous combined HRT was effective for the relief of climacteric symptoms in early postmenopausal women and was well tolerated.
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11. |
- Nik-Zainal, Serena, et al.
(författare)
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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12. |
- Onatsu, J., et al.
(författare)
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Serum Neurofilament Light Chain Concentration Correlates with Infarct Volume but Not Prognosis in Acute Ischemic Stroke
- 2019
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 28:8, s. 2242-2249
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: We studied serum neurofilaments diagnostic value in patients with acute ischemic stroke (AIS) or TIA and evaluated any correlation with symptom severity, cerebral infarction volume, aetiology, and clinical outcome. Methods: One hundred and thirty-six patients (101 with AIS, and 35 with TIA) were included. Acute-phase serum neurofilament light chain (sNfL) was analyzed with a novel ultrasensitive single molecule array (Simoa). Cerebral infarction volume was measured from brain computed tomography in the subacute phase (> 2 days). Stroke aetiology was defined by trial of ORG 10172 in acute stroke treatment classification, severity by National Institute of Health stroke scale (NIHSS) and the degree of disability by the Modified Rankin Scale (mRS) after 90 days. Results: sNfL was markedly higher in patients with AIS (89.5 pg/mL [IQR: 44.7-195.3]) than with TIA (25.2 pg/mL [IQR: 14.6-48.0]), P = <. 001), also after adjusting for age, NIHSS, and stroke volume (P=.003). In receiver operating characteristic analysis, sNfL concentration greater than or equal to 49 pg/mL proved to be the best cut-off value to differentiate between patients with stroke and those with TIA (sensitivity of 73% and specificity of 80%). sNfL concentration significantly correlated with cerebral infarction volume (r = .413, P = < .001), this association remained significant after adjusting for established predictors (P=.019). Patients with AIS due to cardioembolism or large artery atherosclerosis had the highest sNfL concentrations. NIHSS on admission (r = .343, P =< .001) and mRS scores after 3 months (r = .306, P = .004) correlated with sNfL concentration, however functional outcome 3 months after stroke was not associated with sNfL after adjusting for potential confounders. Conclusions: Cases with stroke were distinguishable from those with TIA following the determination of sNfL in the blood samples. The presence and amount of axonal damage estimated by sNfL correlated with the final cerebral infarction volume but was not predictive of degree of disability.
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13. |
- Onatsu, J., et al.
(författare)
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Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events
- 2020
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Ingår i: In Vivo. - : Anticancer Research USA Inc.. - 0258-851X .- 1791-7549. ; 34:5, s. 2577-2586
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: We aimed to analyze the diagnostic value of total tau (T- tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. Patients and Methods: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8 +/- 50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. Results: T-tau was higher in patients with stroke (1.0 pg/ml (IQR=0.3-2 2)] than with TIA (05 pg/ml (IQR=0.2- 1 .0), p=0.02] . The levels of S100B were also increased in stroke [0.082 mu g/l (IQR=0.049-0.157)] patients compared to TIA patients (0.045 mu g/l (IQR=0.03 -0.073 ), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 mu g/l (IQR=9.30-16.14)] compared to those with TIA (10.96 mu g/l (IQR=7 .98-15.33), p=0.301 were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). Conclusion: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months.
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14. |
- Pecl, Gretta T., et al.
(författare)
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Biodiversity redistribution under climate change : Impacts on ecosystems and human well-being
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 355:6332
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Forskningsöversikt (refereegranskat)abstract
- Distributions of Earth's species are changing at accelerating rates, increasingly driven by human-mediated climate change. Such changes are already altering the composition of ecological communities, but beyond conservation of natural systems, how and why does this matter? We review evidence that climate-driven species redistribution at regional to global scales affects ecosystem functioning, human well-being, and the dynamics of climate change itself. Production of natural resources required for food security, patterns of disease transmission, and processes of carbon sequestration are all altered by changes in species distribution. Consideration of these effects of biodiversity redistribution is critical yet lacking in most mitigation and adaptation strategies, including the United Nation's Sustainable Development Goals.
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19. |
- Huhtaniemi, R., et al.
(författare)
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Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts
- 2018
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440. ; 188:12, s. 2890-2901
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Tidskriftsartikel (refereegranskat)abstract
- The role of adrenal androgens as drivers for castration-resistant prostate cancer (CRPC) growth in humans is generally accepted; however, the value of preclinical mouse models of CRPC is debatable, because mouse adrenals do not produce steroids activating the androgen receptor. In this study, we confirmed the expression of enzymes essential for de novo synthesis of androgens in mouse adrenals, with high intratissue concentration of progesterone (P4) and moderate levels of androgens, such as androstenedione, testosterone, and dihydrotestosterone, in the adrenal glands of both intact and orchectomized (ORX) mice. ORX alone had no effect on serum P4 concentration, whereas orchectomized and adrenalectomized (ORX + ADX) resulted in a significant decrease in serum P4 and in a further reduction in the low levels of serum androgens (androstenedione, testosterone, and dihydrotestosterone), measured by mass spectrometry. In line with this, the serum prostate-specific antigen and growth of VCaP xenografts in mice after ORX + ADX were markedly reduced compared with ORX alone, and the growth difference was not abolished by a glucocorticoid treatment. Moreover, ORX + ADX altered the androgen-dependent gene expression in the tumors, similar to that recently shown for the enzalutamide treatment. These data indicate that in contrast to the current view, and similar to humans, mouse adrenals synthesize significant amounts of steroids that contribute to the androgen receptor–dependent growth of CRPC. © 2018 American Society for Investigative Pathology
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20. |
- Huhtaniemi, R., et al.
(författare)
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High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:5
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Tidskriftsartikel (refereegranskat)abstract
- Antiandrogen treatment resistance is a major clinical concern in castration-resistant prostate cancer (CRPC) treatment. Using xenografts of VCaP cells we showed that growth of antiandrogen resistant CRPC tumors were characterized by a higher intratumor dihydrotestosterone (DHT) concentration than that of treatment responsive tumors. Furthermore, the slow tumor growth after adrenalectomy was associated with a low intratumor DHT concentration. Reactivation of androgen signaling in enzalutamide-resistant tumors was further shown by the expression of several androgen-dependent genes. The data indicate that intratumor DHT concentration and expression of several androgen-dependent genes in CRPC lesions is an indication of enzalutamide treatment resistance and an indication of the need for further androgen blockade. The presence of an androgen synthesis, independent of CYP17A1 activity, has been shown to exist in prostate cancer cells, and thus, novel androgen synthesis inhibitors are needed for the treatment of enzalutamide-resistant CRPC tumors that do not respond to abiraterone.
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21. |
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22. |
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24. |
- Alexandrov, Ludmil B, et al.
(författare)
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The repertoire of mutational signatures in human cancer
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.
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25. |
- Andersson, Erik, et al.
(författare)
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Ambio fit for the 2020s
- 2022
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Ingår i: Ambio. - : Springer Nature. - 0044-7447 .- 1654-7209. ; 51:5, s. 1091-1093
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Tidskriftsartikel (refereegranskat)
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26. |
- Arason, Adalgeir, et al.
(författare)
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Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families
- 2010
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:4, s. R50-
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.
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27. |
- Bergström, Anders, et al.
(författare)
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A high-definition view of functional genetic variation from natural yeast genomes.
- 2014
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 31:4, s. 872-88
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Tidskriftsartikel (refereegranskat)abstract
- The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies.
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29. |
- Halttunen, Jorma, et al.
(författare)
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Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs
- 2014
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 49:6, s. 752-758
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Tidskriftsartikel (refereegranskat)abstract
- Background. The definition of a "difficult" cannulation varies considerably in reports of endoscopic retrograde cholangiopancreatography (ERCP). Aims. To define a difficult cannulation, which translates into higher risk of post-ERCP pancreatitis. Patients and methods. Prospective consecutive recording of 907 cannulations in Scandinavian centers done by experienced endoscopists. Inclusion: indication for biliary access in patients with intact papilla. Exclusion: acute non-biliary and chronic pancreatitis at time of procedure. Results. The primary cannulation succeeded in 74.9%, with median values for time 0.88 min (53 s), with two attempts and with zero pancreatic passages or injections. The overall cannulation success was 97.4% and post-ERCP pancreatitis (PEP) rate was 5.3%. The median time for all successful cannulations was 1.55 min (range 0.02-94.2). If the primary cannulation succeeded, the pancreatitis rate was 2.8%; after secondary methods, it rose to 11.5%. Procedures lasting less than 5 min had a PEP rate of 2.6% versus 11.8% in those lasting longer. With one attempt, the PEP rate was 0.6%, with two 3.1%, with three to four 6.1%, and with five and more 11.9%. With one accidental pancreatic guide-wire passage, the risk of the PEP was 3.7%, and with two passages, it was 13.1%. Conclusions. If the increasing rate of PEP is taken as defining factor, the wire-guided cannulation of a native papilla can be considered difficult after 5 min, five attempts, and two pancreatic guide-wire passages when any of those limits is exceeded.
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30. |
- Iheozor-Ejiofor, Rommel, et al.
(författare)
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Neutralizing Antibody Titers in Hospitalized Patients with Acute Puumala Orthohantavirus Infection Do Not Associate with Disease Severity
- 2022
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.
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31. |
- Kordas, K., et al.
(författare)
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Magnetic-field induced efficient alignment of carbon nanotubes in aqueous solutions
- 2007
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 19:4, s. 787-791
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Tidskriftsartikel (refereegranskat)abstract
- Efficient alignment of aqueous carboxyl-functionalized multiwalled carbon nanotubes having remanent iron catalyst particles are carried out in relatively low external magnetic fields (B <= 1017 mT). The nanotubes were grown by catalytic chemical vapor deposition and then functionalized in a multistep oxidation process using nitric acid and potassium permanganate. In the field-induced ordering, the ferromagnetic property of iron nanoparticles entrapped in the inner-tubular cavity of nanotubes is exploited. Considerable dichroism of nanotube solutions (up to 3.02) is measured and deposition of aligned CNT networks from the solutions on silicon substrates is demonstrated.
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32. |
- Moilanen, A. M., et al.
(författare)
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WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims In a recent genome-wide association study, WD-repeat domain 12 (WDR12) was associated with early-onset myocardial infarction (MI). However, the function of WDR12 in the heart is unknown. We characterized cardiac expression of WDR12, used adenovirus-mediated WDR12 gene delivery to examine effects of WDR12 on left ventricular (LV) remodeling, and analyzed relationship between MI associated WDR12 allele and cardiac function in human subjects. LV WDR12 protein levels were increased in patients with dilated cardiomyopathy and rats post-infarction. In normal adult rat hearts, WDR12 gene delivery into the anterior wall of the LV decreased interventricular septum diastolic and systolic thickness and increased the diastolic and systolic diameters of the LV. Moreover, LV ejection fraction (9.1%, P<0.05) and fractional shortening (12.2%, P<0.05) were declined. The adverse effects of WDR12 gene delivery on cardiac function were associated with decreased cellular proliferation, activation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein (HSP) 27 pathway, and increased protein levels of Block of proliferation 1 (BOP1), essential for ribosome biogenesis. Post-infarction WDR12 gene delivery decreased E/A ratio (32%, P<0.05) suggesting worsening of diastolic function. In human subjects, MI associated WDR12 allele was associated significantly with diastolic dysfunction and left atrial size. WDR12 triggers distinct deterioration of cardiac function in adult rat heart and the MI associated WDR12 variant is associated with diastolic dysfunction in human subjects.
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34. |
- Oresic, Matej, 1967-, et al.
(författare)
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Phospholipids and insulin resistance in psychosis : A lipidomics study of twin pairs discordant for schizophrenia
- 2012
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.Methods: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 +/- 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
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- Plyusnin, A, et al.
(författare)
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Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents
- 1997
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Ingår i: Journal of clinical microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 35:5, s. 1090-1096
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Tidskriftsartikel (refereegranskat)abstract
- Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.
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