84 results on '"Kjell Petersen"'
Search Results
2. Transcriptome-wide analyses of early immune responses in lumpfish leukocytes upon stimulation with poly(I:C)
- Author
-
Shreesha S. Rao, Harald S. Lunde, David W. P. Dolan, Amanda K. Fond, Kjell Petersen, and Gyri T. Haugland
- Subjects
poly(I:C) ,lumpfish ,transcriptome ,DEG ,omics ,RIG-I signaling pathway ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundBoth bacterial and viral diseases are a major threat to farmed fish. As the antiviral immune mechanisms in lumpfish (Cyclopterus lumpus L.) are poorly understood, lumpfish leukocytes were stimulated with poly(I:C), a synthetic analog of double stranded RNA, which mimic viral infections, and RNA sequencing was performed.MethodsTo address this gap, we stimulated lumpfish leukocytes with poly(I:C) for 6 and 24 hours and did RNA sequencing with three parallels per timepoint. Genome guided mapping was performed to define differentially expressed genes (DEGs).ResultsImmune genes were identified, and transcriptome-wide analyses of early immune responses showed that 376 and 2372 transcripts were significantly differentially expressed 6 and 24 hours post exposure (hpe) to poly(I:C), respectively. The most enriched GO terms when time had been accounted for, were immune system processes (GO:0002376) and immune response (GO:0006955). Analysis of DEGs showed that among the most highly upregulated genes were TLRs and genes belonging to the RIG-I signaling pathway, including LGP2, STING and MX, as well as IRF3 and IL12A. RIG-I was not identified, but in silico analyses showed that genes encoding proteins involved in pathogen recognition, cell signaling, and cytokines of the TLR and RIG-I signaling pathway are mostly conserved in lumpfish when compared to mammals and other teleost species.ConclusionsOur analyses unravel the innate immune pathways playing a major role in antiviral defense in lumpfish. The information gathered can be used in comparative studies and lay the groundwork for future functional analyses of immune and pathogenicity mechanisms. Such knowledge is also necessary for the development of immunoprophylactic measures for lumpfish, which is extensively cultivated for use as cleaner fish in the aquaculture for removal of sea lice from Atlantic salmon (Salmo salar L.).
- Published
- 2023
- Full Text
- View/download PDF
3. Common gene expression signatures in Parkinson’s disease are driven by changes in cell composition
- Author
-
Gonzalo S. Nido, Fiona Dick, Lilah Toker, Kjell Petersen, Guido Alves, Ole-Bjørn Tysnes, Inge Jonassen, Kristoffer Haugarvoll, and Charalampos Tzoulis
- Subjects
RNA sequencing ,Neurodegeneration ,Parkinsonism ,Mitochondria ,Gene expression ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract The etiology of Parkinson’s disease is largely unknown. Genome-wide transcriptomic studies in bulk brain tissue have identified several molecular signatures associated with the disease. While these studies have the potential to shed light into the pathogenesis of Parkinson’s disease, they are also limited by two major confounders: RNA post-mortem degradation and heterogeneous cell type composition of bulk tissue samples. We performed RNA sequencing following ribosomal RNA depletion in the prefrontal cortex of 49 individuals from two independent case-control cohorts. Using cell type specific markers, we estimated the cell type composition for each sample and included this in our analysis models to compensate for the variation in cell type proportions. Ribosomal RNA depletion followed by capture by random primers resulted in substantially more even transcript coverage, compared to poly(A) capture, in post-mortem tissue. Moreover, we show that cell type composition is a major confounder of differential gene expression analysis in the Parkinson’s disease brain. Accounting for cell type proportions attenuated numerous transcriptomic signatures that have been previously associated with Parkinson’s disease, including vesicle trafficking, synaptic transmission, immune and mitochondrial function. Conversely, pathways related to endoplasmic reticulum, lipid oxidation and unfolded protein response were strengthened and surface as the top differential gene expression signatures in the Parkinson’s disease prefrontal cortex. Our results indicate that differential gene expression signatures in Parkinson’s disease bulk brain tissue are significantly confounded by underlying differences in cell type composition. Modeling cell type heterogeneity is crucial in order to unveil transcriptomic signatures that represent regulatory changes in the Parkinson’s disease brain and are, therefore, more likely to be associated with underlying disease mechanisms.
- Published
- 2020
- Full Text
- View/download PDF
4. Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis
- Author
-
Terje Sundstrøm, Lars Prestegarden, Francisco Azuaje, Synnøve Nymark Aasen, Gro Vatne Røsland, Jobin K. Varughese, Marzieh Bahador, Simon Bernatz, Yannick Braun, Patrick N. Harter, Kai Ove Skaftnesmo, Elizabeth S. Ingham, Lisa M. Mahakian, Sarah Tam, Clifford G. Tepper, Kjell Petersen, Katherine W. Ferrara, Karl Johan Tronstad, Morten Lund-Johansen, Rudi Beschorner, Rolf Bjerkvig, and Frits Thorsen
- Subjects
Cancer ,Melanoma ,Brain metastasis ,BRAF V600E ,β-Sitosterol ,Treatment ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Melanoma patients carry a high risk of developing brain metastases, and improvements in survival are still measured in weeks or months. Durable disease control within the brain is impeded by poor drug penetration across the blood-brain barrier, as well as intrinsic and acquired drug resistance. Augmented mitochondrial respiration is a key resistance mechanism in BRAF-mutant melanomas but, as we show in this study, this dependence on mitochondrial respiration may also be exploited therapeutically. We first used high-throughput pharmacogenomic profiling to identify potentially repurposable compounds against BRAF-mutant melanoma brain metastases. One of the compounds identified was β-sitosterol, a well-tolerated and brain-penetrable phytosterol. Here we show that β-sitosterol attenuates melanoma cell growth in vitro and also inhibits brain metastasis formation in vivo. Functional analyses indicated that the therapeutic potential of β-sitosterol was linked to mitochondrial interference. Mechanistically, β-sitosterol effectively reduced mitochondrial respiratory capacity, mediated by an inhibition of mitochondrial complex I. The net result of this action was increased oxidative stress that led to apoptosis. This effect was only seen in tumor cells, and not in normal cells. Large-scale analyses of human melanoma brain metastases indicated a significant role of mitochondrial complex I compared to brain metastases from other cancers. Finally, we observed completely abrogated BRAF inhibitor resistance when vemurafenib was combined with either β-sitosterol or a functional knockdown of mitochondrial complex I. In conclusion, based on its favorable tolerability, excellent brain bioavailability, and capacity to inhibit mitochondrial respiration, β-sitosterol represents a promising adjuvant to BRAF inhibitor therapy in patients with, or at risk for, melanoma brain metastases.
- Published
- 2019
- Full Text
- View/download PDF
5. Norwegian e-Infrastructure for Life Sciences (NeLS) [version 1; referees: 2 approved]
- Author
-
Kidane M. Tekle, Sveinung Gundersen, Kjetil Klepper, Lars Ailo Bongo, Inge Alexander Raknes, Xiaxi Li, Wei Zhang, Christian Andreetta, Teshome Dagne Mulugeta, Matúš Kalaš, Morten B. Rye, Erik Hjerde, Jeevan Karloss Antony Samy, Ghislain Fornous, Abdulrahman Azab, Dag Inge Våge, Eivind Hovig, Nils Peder Willassen, Finn Drabløs, Ståle Nygård, Kjell Petersen, and Inge Jonassen
- Subjects
Medicine ,Science - Abstract
The Norwegian e-Infrastructure for Life Sciences (NeLS) has been developed by ELIXIR Norway to provide its users with a system enabling data storage, sharing, and analysis in a project-oriented fashion. The system is available through easy-to-use web interfaces, including the Galaxy workbench for data analysis and workflow execution. Users confident with a command-line interface and programming may also access it through Secure Shell (SSH) and application programming interfaces (APIs). NeLS has been in production since 2015, with training and support provided by the help desk of ELIXIR Norway. Through collaboration with NorSeq, the national consortium for high-throughput sequencing, an integrated service is offered so that sequencing data generated in a research project is provided to the involved researchers through NeLS. Sensitive data, such as individual genomic sequencing data, are handled using the TSD (Services for Sensitive Data) platform provided by Sigma2 and the University of Oslo. NeLS integrates national e-infrastructure storage and computing resources, and is also integrated with the SEEK platform in order to store large data files produced by experiments described in SEEK. In this article, we outline the architecture of NeLS and discuss possible directions for further development.
- Published
- 2018
- Full Text
- View/download PDF
6. Identification of highly connected and differentially expressed gene subnetworks in metastasizing endometrial cancer.
- Author
-
Kanthida Kusonmano, Mari K Halle, Elisabeth Wik, Erling A Hoivik, Camilla Krakstad, Karen K Mauland, Ingvild L Tangen, Anna Berg, Henrica M J Werner, Jone Trovik, Anne M Øyan, Karl-Henning Kalland, Inge Jonassen, Helga B Salvesen, and Kjell Petersen
- Subjects
Medicine ,Science - Abstract
We have identified nine highly connected and differentially expressed gene subnetworks between aggressive primary tumors and metastatic lesions in endometrial carcinomas. We implemented a novel pipeline combining gene set and network approaches, which here allows integration of protein-protein interactions and gene expression data. The resulting subnetworks are significantly associated with disease progression across tumor stages from complex atypical hyperplasia, primary tumors to metastatic lesions. The nine subnetworks include genes related to metastasizing features such as epithelial-mesenchymal transition (EMT), hypoxia and cell proliferation. TCF4 and TWIST2 were found as central genes in the subnetwork related to EMT. Two of the identified subnetworks display statistically significant association to patient survival, which were further supported by an independent validation in the data from The Cancer Genome Atlas data collection. The first subnetwork contains genes related to cell proliferation and cell cycle, while the second contains genes involved in hypoxia such as HIF1A and EGLN3. Our findings provide a promising context to elucidate the biological mechanisms of metastasis, suggest potential prognostic markers and further identify therapeutic targets. The pipeline R source code is freely available, including permutation tests to assess statistical significance of the identified subnetworks.
- Published
- 2018
- Full Text
- View/download PDF
7. Switch in FOXA1 status associates with endometrial cancer progression.
- Author
-
Ingvild Løberg Tangen, Camilla Krakstad, Mari K Halle, Henrica M J Werner, Anne M Oyan, Kanthida Kusonmano, Kjell Petersen, Karl Henning Kalland, Lars A Akslen, Jone Trovik, Antoni Hurtado, and Helga B Salvesen
- Subjects
Medicine ,Science - Abstract
BACKGROUND: The transcription factor Forkhead box A1 (FOXA1) is suggested to be important in hormone dependent cancers, although with little data for endometrial cancer. We investigated expression levels of FOXA1 in primary and metastatic endometrial cancer in relation to clinical phenotype, and transcriptional alterations related to FOXA1 status. METHODS: Protein expression of FOXA1 was explored by immunohistochemistry in 529 primary and 199 metastatic endometrial carcinoma lesions. mRNA levels from corresponding 158 fresh frozen primary and 42 metastatic lesions were analyzed using Agilent Microarrays (44k) in parallel. RESULTS: Low FOXA1 protein expression in primary tumors significantly correlated with low FOXA1 mRNA, high age, non-endometrioid histology, high grade, loss of ERα and PR and poor survival (all p-values
- Published
- 2014
- Full Text
- View/download PDF
8. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model.
- Author
-
Kjell Petersen, Uros Rajcevic, Siti Aminah Abdul Rahim, Inge Jonassen, Karl-Henning Kalland, Connie R Jimenez, Rolf Bjerkvig, and Simone P Niclou
- Subjects
Medicine ,Science - Abstract
A key challenge in the data analysis of biological high-throughput experiments is to handle the often low number of samples in the experiments compared to the number of biomolecules that are simultaneously measured. Combining experimental data using independent technologies to illuminate the same biological trends, as well as complementing each other in a larger perspective, is one natural way to overcome this challenge. In this work we investigated if integrating proteomics and transcriptomics data from a brain cancer animal model using gene set based analysis methodology, could enhance the biological interpretation of the data relative to more traditional analysis of the two datasets individually. The brain cancer model used is based on serial passaging of transplanted human brain tumor material (glioblastoma--GBM) through several generations in rats. These serial transplantations lead over time to genotypic and phenotypic changes in the tumors and represent a medically relevant model with a rare access to samples and where consequent analyses of individual datasets have revealed relatively few significant findings on their own. We found that the integrated analysis both performed better in terms of significance measure of its findings compared to individual analyses, as well as providing independent verification of the individual results. Thus a better context for overall biological interpretation of the data can be achieved.
- Published
- 2013
- Full Text
- View/download PDF
9. Somatic maintenance resources in the honeybee worker fat body are distributed to withstand the most life-threatening challenges at each life stage.
- Author
-
Siri-Christine Seehuus, Simon Taylor, Kjell Petersen, and Randi M Aamodt
- Subjects
Medicine ,Science - Abstract
In a global transcriptome analysis of three natural and three manipulated honeybee worker phenotypes at different ages, we have investigated the distribution of investment in somatic maintenance of the fat body. Gene expression is modulated so that the bees are able to resist the most life-threatening challenges at the actual life stage. Different modes of maintenance and repair are regulated, apparently to meet the environmental challenges most detrimental to survival and reproductive potential for the hive. We observed a broad down-regulation of genomic and cellular maintenance in the short-lived foragers and nurse bees compared to the long-lived winter bees. Our results show that survival and reproduction of the entire hive is given priority over the individual bees, hence supporting the idea of the honeybee society as a superorganism. Our results also fit the disposable soma theory of aging.
- Published
- 2013
- Full Text
- View/download PDF
10. High-throughput mutation profiling of primary and metastatic endometrial cancers identifies KRAS, FGFR2 and PIK3CA to be frequently mutated.
- Author
-
Camilla Krakstad, Even Birkeland, Danila Seidel, Kanthida Kusonmano, Kjell Petersen, Siv Mjøs, Erling A Hoivik, Elisabeth Wik, Mari Kyllesø Halle, Anne M Øyan, Karl-Henning Kalland, Henrica Maria Johanna Werner, Jone Trovik, and Helga Salvesen
- Subjects
Medicine ,Science - Abstract
Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with metastatic endometrial carcinoma. In order to improve treatment, underlying molecular characteristics of primary and metastatic disease must be explored.We utilized the mass spectrometric-based mutation detection technology OncoMap to define the types and frequency of point somatic mutations in endometrial cancer. 67 primary tumors, 15 metastases corresponding to 7 of the included primary tumors and 11 endometrial cancer cell lines were screened for point mutations in 28 known oncogenes. We found that 27 (40.3%) of 67 primary tumors harbored one or more mutations with no increase in metastatic lesions. FGFR2, KRAS and PIK3CA were consistently the most frequently mutated genes in primary tumors, metastatic lesions and cell lines.Our results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies.
- Published
- 2012
- Full Text
- View/download PDF
11. Genome-wide profiling of histone h3 lysine 4 and lysine 27 trimethylation reveals an epigenetic signature in prostate carcinogenesis.
- Author
-
Xi-Song Ke, Yi Qu, Kari Rostad, Wen-Cheng Li, Biaoyang Lin, Ole Johan Halvorsen, Svein A Haukaas, Inge Jonassen, Kjell Petersen, Naomi Goldfinger, Varda Rotter, Lars A Akslen, Anne M Oyan, and Karl-Henning Kalland
- Subjects
Medicine ,Science - Abstract
BackgroundIncreasing evidence implicates the critical roles of epigenetic regulation in cancer. Very recent reports indicate that global gene silencing in cancer is associated with specific epigenetic modifications. However, the relationship between epigenetic switches and more dynamic patterns of gene activation and repression has remained largely unknown.Methodology/principal findingsGenome-wide profiling of the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) was performed using chromatin immunoprecipitation coupled with whole genome promoter microarray (ChIP-chip) techniques. Comparison of the ChIP-chip data and microarray gene expression data revealed that loss and/or gain of H3K4me3 and/or H3K27me3 were strongly associated with differential gene expression, including microRNA expression, between prostate cancer and primary cells. The most common switches were gain or loss of H3K27me3 coupled with low effect on gene expression. The least prevalent switches were between H3K4me3 and H3K27me3 coupled with much higher fractions of activated and silenced genes. Promoter patterns of H3K4me3 and H3K27me3 corresponded strongly with coordinated expression changes of regulatory gene modules, such as HOX and microRNA genes, and structural gene modules, such as desmosome and gap junction genes. A number of epigenetically switched oncogenes and tumor suppressor genes were found overexpressed and underexpressed accordingly in prostate cancer cells.Conclusions/significanceThis work offers a dynamic picture of epigenetic switches in carcinogenesis and contributes to an overall understanding of coordinated regulation of gene expression in cancer. Our data indicate an H3K4me3/H3K27me3 epigenetic signature of prostate carcinogenesis.
- Published
- 2009
- Full Text
- View/download PDF
12. Judi Wingard and Merv Wingard Interview, February 17, 2024
- Author
-
Mark Huftstetler; C. Kjell Petersen; Beth Hodder, Wingard, Judith Marie, Wingard, Mervin Elliott, Mark Huftstetler; C. Kjell Petersen; Beth Hodder, Wingard, Judith Marie, and Wingard, Mervin Elliott
- Abstract
Merv and Judi Wingard share their experiences as lookouts at Numa Ridge and Apgar in Glacier National Park in 1968 and 1969. Judi reflects on her idyllic childhood in Washington, filled with nature and supportive neighbors. Merv shares his love for nature and mountain climbing, influenced by his family's logging background and experiences in the mountains. The couple discusses life in a remote wilderness lookout. A constant in their lives was Ron, a seasoned packer for both Numa Ridge and Apgar. He provided food and entertainment with his unique personality. Judi and Merv discuss painting the interior of the lookout with Forest Service green, red, gray, and white, adding a racing stripe on the ceiling and floor. They mention cleaning the cabins, doing cabinetry work, and building a new outhouse at Numa Ridge. They remember the training they received before going to Numa Ridge, including a week of training with married couples. They share details about how they communicated with each other during their time at Apgar Lookout, including using the fire cache as a hub for communication. They recount learning how to use a fire finder and build a fire trail. They remember aerial observers would drop mail and supplies at the lookout, using precision to land near the stairway. They discuss the challenges of living without refrigeration, with limited access to fresh vegetables. Merv and Judi discuss their experiences with grizzly bears and the death of ranger Karol Hagen in a flooded river. Other highlights they mention were working on a film set and building a platform for a helicopter. They said from their experiences as lookouts they learned contentment and enjoying moments beyond the lookout.
- Published
- 2024
13. Betty Violette Interview, February 14, 2024
- Author
-
Mark Hufstetler; C. Kjell Petersen; Beth Hodder, Violette, Betty Ann, Mark Hufstetler; C. Kjell Petersen; Beth Hodder, and Violette, Betty Ann
- Abstract
Betty Violette shares stories of her eleven seasons as a fire lookout in Montana's Flathead National Forest (FNF) and Kootenai National Forest (KNF). Betty grew up in St. Ignatius, Montana, and struggled to find her career path. She discusses wanting to be an artist but working in New York City made her realize that wasn’t for her. She then became a lookout in 1966. Betty describes working at Kenalty Lookout in the KNF, where she hiked to get there. She enjoyed a cat as her companion. She recalls radio communications, weather duties, and successfully reporting a fire. She recounts encountering a moose, a humorous encounter with a badger, and a packrat that left sticks on the catwalk. Through the 1960s and 1970s, she talks of using metal cans for water, using the same water for washing dishes and clothes and bathing. She says she worked long hours with limited breaks and constant monitoring. She recounts a storm hitting one of her towers, causing damage, and a near miss with lightning. Betty talks of enjoying the solitude on lookouts, staying a whole season without returning to town. She talks of being thrilled to work at Baptiste Lookout in the 1970s. She said she believes she was the last lookout at Baptiste and Cyclone and possibly Firefighter Lookouts before they closed [All three FNF lookouts are now open again]. Betty says being a lookout shaped her life because it kept her in an outdoor environment in Montana.
- Published
- 2024
14. Early adopter PoC nodes operational with synthetic data
- Author
-
Kjell Petersen
- Subjects
European Genomic Data Infrastructure ,1+MG ,GDI - Abstract
Document showing the status of the Vanguard (early adopter) Nodes as of June 2023 in the European Genomic Data Infrastructure project.
- Published
- 2023
- Full Text
- View/download PDF
15. Mark Hufstetler Interview, January 30, 2023
- Author
-
Beth Hodder: Kjell Petersen, Hufstetler, Mark, Beth Hodder: Kjell Petersen, and Hufstetler, Mark
- Abstract
In this second interview, Mark focuses on the Flathead National Forest’s volunteer program, which he says is a “unique opportunity for the community” by having volunteers who do all the duties of regular lookouts for ten days to two weeks. He says the volunteers have two days of training to learn weather, the firefinder, radios, and other equipment and duties. Mark tells of the uniqueness of lookouts he has staffed, like Baptiste’s remoteness, and the great interplay of weather. Cyclone Lookout has a view of Glacier National Park that Mark says equals or exceeds what tourists can see in the park. At Porphyry Lookout, he tells of being the only lookout for one hundred miles, but you can drive to the lookout, so there is no solitude. Mark talks about his own unique duties: working with main lookout, Leif Haugen, before lookouts return, helping with volunteer and Forest Service training, response to fires, and updating manuals. He discusses how things change seasonally and says he is gratified by learning self-reliance as a result of his lookout experiences.
- Published
- 2023
16. Supplementary Table 1 from High Phospho-Stathmin(Serine38) Expression Identifies Aggressive Endometrial Cancer and Suggests an Association with PI3K Inhibition
- Author
-
Helga B. Salvesen, Lars A. Akslen, William Ricketts, Karl H. Kalland, Ronald Simon, Anne M. Oyan, Kjell Petersen, Frederik Holst, Ingunn M. Stefansson, Karen Mauland, Kanthida Kusonmano, Camilla Krakstad, Siv Mjos, Erling A. Hoivik, Henrica M.J. Werner, Jone Trovik, Even Birkeland, and Elisabeth Wik
- Abstract
PDF file - 50K, Primary investigation series. Cox's proportional hazard regression model used to estimate the prognostic value of pStathmin(S38) in endometrial carcinomas, in relation to histopathologic variables and Stathmin.
- Published
- 2023
17. Supplementary Table 3 from High Phospho-Stathmin(Serine38) Expression Identifies Aggressive Endometrial Cancer and Suggests an Association with PI3K Inhibition
- Author
-
Helga B. Salvesen, Lars A. Akslen, William Ricketts, Karl H. Kalland, Ronald Simon, Anne M. Oyan, Kjell Petersen, Frederik Holst, Ingunn M. Stefansson, Karen Mauland, Kanthida Kusonmano, Camilla Krakstad, Siv Mjos, Erling A. Hoivik, Henrica M.J. Werner, Jone Trovik, Even Birkeland, and Elisabeth Wik
- Abstract
PDF file - 84K, Gene Set Enrichment Analysis (www.broadinstitute.org/gsea/msigdb). Gene sets (GO categories, computational gene sets and curated gene sets) within FDR
- Published
- 2023
18. Supplementary Table 2 from High Phospho-Stathmin(Serine38) Expression Identifies Aggressive Endometrial Cancer and Suggests an Association with PI3K Inhibition
- Author
-
Helga B. Salvesen, Lars A. Akslen, William Ricketts, Karl H. Kalland, Ronald Simon, Anne M. Oyan, Kjell Petersen, Frederik Holst, Ingunn M. Stefansson, Karen Mauland, Kanthida Kusonmano, Camilla Krakstad, Siv Mjos, Erling A. Hoivik, Henrica M.J. Werner, Jone Trovik, Even Birkeland, and Elisabeth Wik
- Abstract
PDF file - 50K, Validations series. Cox's proportional hazard regression model used to estimate the prognostic value of pStathmin(S38) in endometrial carcinomas, in relation to histopathologic variables and Stathmin.
- Published
- 2023
19. Supplementary Figure 2 from High Phospho-Stathmin(Serine38) Expression Identifies Aggressive Endometrial Cancer and Suggests an Association with PI3K Inhibition
- Author
-
Helga B. Salvesen, Lars A. Akslen, William Ricketts, Karl H. Kalland, Ronald Simon, Anne M. Oyan, Kjell Petersen, Frederik Holst, Ingunn M. Stefansson, Karen Mauland, Kanthida Kusonmano, Camilla Krakstad, Siv Mjos, Erling A. Hoivik, Henrica M.J. Werner, Jone Trovik, Even Birkeland, and Elisabeth Wik
- Abstract
PDF file - 40K, Unsupervised hierarchical clustering of gene expression data from endometrial carcinoma. The pStathmin(S38) high cases are significantly overrepresented in two of the clusters with aggressive tumors.
- Published
- 2023
20. Data from High Phospho-Stathmin(Serine38) Expression Identifies Aggressive Endometrial Cancer and Suggests an Association with PI3K Inhibition
- Author
-
Helga B. Salvesen, Lars A. Akslen, William Ricketts, Karl H. Kalland, Ronald Simon, Anne M. Oyan, Kjell Petersen, Frederik Holst, Ingunn M. Stefansson, Karen Mauland, Kanthida Kusonmano, Camilla Krakstad, Siv Mjos, Erling A. Hoivik, Henrica M.J. Werner, Jone Trovik, Even Birkeland, and Elisabeth Wik
- Abstract
Purpose: High Stathmin expression has recently been associated with clinical progress in endometrial cancers. Stathmin protein activity is modulated by phosphorylation, and the Serine38 site is one of four Stathmin phospho-sites. The presence and significance of pStathmin(S38) is largely unknown in human cancers, and we here examined the associations between this marker and tumor cell proliferation, clinicopathologic phenotype, and survival impact in endometrial cancer. A relationship with possible treatment targets was explored by integrated analysis of transcriptional alterations.Experimental Design: Primary endometrial cancers from two independent patient series (n = 518/n = 286) were analyzed. Biomarkers were assessed by immunohistochemistry, FISH, flow cytometry, DNA oligonucleotide microarray, single-nucleotide polymorphism array, and Sanger sequencing, and related to clinicopathologic annotations and follow-up information.Results: High pStathmin(S38) level was associated with poor prognosis, independent of other features, and correlated to increased tumor cell proliferation as well as high Stathmin levels. On the basis of transcriptional differences between high/low pStathmin(S38) tumors, phosphoinositide 3-kinase (PI3K)/mTOR/HSP90 were suggested as possible targets in pStathmin(S38)-high cases. High pStathmin(S38) was associated with several PI3K pathway alterations: amplification of the 3q26 region, increased PIK3CA copy number (FISH) and a PI3K activation score (all P < 0.05).Conclusions: High pStathmin(S38) is a novel biomarker of increased tumor cell proliferation and impaired prognosis as reported here for independent cohorts of endometrial cancer and not previously shown in human cancer. Our data support a rationale for further studies exploring effects of drugs inhibiting the PI3K signaling pathway in pStathmin(S38)-high endometrial cancer, including a potential value of pStathmin(S38) in predicting response to PI3K/mTOR/HSP90 inhibitors. Clin Cancer Res; 19(9); 2331–41. ©2013 AACR.
- Published
- 2023
21. Direct data transfer between SOAP web services in orchestration.
- Author
-
Sattanathan Subramanian, Pawel Sztromwasser, Kjell Petersen, and Pål Puntervoll
- Published
- 2012
- Full Text
- View/download PDF
22. Leif Haugen Interview, January 5, 2022
- Author
-
Beth Hodder, Kjell Petersen, Haugen, Leif David, Beth Hodder, Kjell Petersen, and Haugen, Leif David
- Abstract
This interview spans Leif Haugen’s entire lookout career: Mount Morrell, Mt. Henry, Numa Ridge, and Thoma. Along with experiences on the lookouts, Leif discusses knowledge and experience he gained on how to live on a lookout and do a quality job; the Park Service and Forest Service organizations; and his role in creating the volunteer lookout program for the Forest Service. Leif is a lead lookout for the Park Service and Forest Service and heads the volunteer program.
- Published
- 2022
23. Brian Miller Interview, June 20, 2022
- Author
-
Beth Hodder: Kjell Petersen, Miller, Brian, Beth Hodder: Kjell Petersen, and Miller, Brian
- Abstract
Brian shares being born in Indiana but his family moved to Montana when he was four. He tells of living in Potomac, where he also went to school. He says playing outdoors led to a “wild imagination. Brian talks of growing up with his father, Gene Miller, on lookouts starting at age five, spending twelve years over his lifetime on lookouts, with most experiences being on Blue Mountain, Mormon, Sliderock, Morrell, and West Fork Butte Lookouts. Brian recalls his dad telling him that as a youth he entertained visitors with stories, landmarks, peaks, etc. He remembers wildlife sightings, flying paper airplanes, playing with Lincoln Logs, hooking rugs, picking huckleberries for Gene’s pies, and hiking to other lookouts. Brian recalls a strenuous backpack trip with his cousin because of carrying lots of canned food, learning to cook on a woodstove, vandalism on Blue Mountain Lookout, drunks at the lookout at night, and learning to read Forest Service maps and clouds. Brian describes lookout people as resilient and introverted.
- Published
- 2022
24. Brian Miller Interview, July 11, 2022
- Author
-
Beth Hodder: Kjell Petersen, Miller, Brian, Beth Hodder: Kjell Petersen, and Miller, Brian
- Abstract
In Brian Miller’s second interview, he remembers being five years old with his father, Gene Miller, on Mormon Peak Lookout. He recalls his mother and sister visiting when his mother rushed Gene to the hospital for gall bladder surgery. Brian tells of being on Sliderock Lookout next, which had a microwave repeater nearby, affording the lookout with electricity. Sliderock also had a cabin at the base of the lookout, a small rundown cabin next to the lookout, and the original lookout: a tree with rungs nailed to it. Brian says there was an old ghost town on the way up the road. He recalls his uncle’s car losing the oil pan on the way down, and they had to walk for help. He discussed the 1988 fires; walking from Mexico to Canada in 1993 along the Continental Divide; and exploring and renting these lookouts, some while skiing to them with his wife: West Fork Butte, McGuire, Hornet, Mt. Wam, Webb Mountain, and Stahl Peak. Brian talks about Sliderock Lookout being moved by helicopter to Fort Missoula as a museum piece. Brian says his strongest memories of being a lookout are dramatic weather and the people he has met.
- Published
- 2022
25. Mark Hufstetler Interview, November 29, 2022
- Author
-
Beth Hodder: Kjell Petersen, Hufstetler, Mark, Beth Hodder: Kjell Petersen, and Hufstetler, Mark
- Abstract
Mark Hufstetler describes being born in Utah in 1958. He says his father was a career U.S. Forest Service employee, and Mark’s family lived at Forest Service ranger stations within the Challis, Bridger, and Dixie National Forests until his family purchased a homestead in the Uinta Mountains. Mark tells of visiting Twin Peaks and Fly Creek Point Lookouts in 1966, sparking an interest in lookouts. After attending college in Salt Lake City, Mark describes spending six years with Glacier National Park concessions, where he visited many lookouts. Mark discusses getting his master’s degree at Montana State University and then working as a historian in Glacier National Park. He describes working with the Flathead National Forest as a volunteer lookout for 24 days on Cooney, Cyclone, and Baptiste Lookouts. In 2018, Mark staffed Porphyry Peak Lookout with the Lewis and Clark National Forest before returning in 2019 to Baptiste Lookout as a paid staffer. Mark says he has worked there ever since and plans to return in 2023.
- Published
- 2022
26. Small-Signal Stability Analysis of GridVille's Microgrid
- Author
-
Synstad, Kjell Petersen, Amin, Mohammad, and Shankar Gupta, Yusuf
- Abstract
Denne oppgaven har som mål å analysere mikronettet til GridVille, en studentorganisasjon som skal bygge et micronett for en landsby i Nepal, for å comme med praktiske forslag til hvordan å forbedre stabiliteten i energisystemet. De praktiske forslagene som blir nevn blir konkretisert ved å undersøke effekten av å endre spenningen, statikk, sammenkoblede linjer og fordeling av last. For å analysere micronettet, ble artikkelen \textit{Reduced-order model and stability analysis of low-voltage DC microgrid} av Sandeep Anand og Baylon G. Fernandes brukt som grunnlag. Modellen i artikkelen ble rekonstruert og en ny modell for GridVille sitt micronett ble utviklet med artikkelen som grunnlag. Linjestrømmene og kildestrømmene har den samme responsen, men tidsaksen er forskjellig mellom artikkelen og den de rekonstruerte modellen. For representasjonen av GridVille, så følger responsen et likt mønster sammenlignet med artikkelen og blir derfor brukt for videre analyse. Resultatene viser at det ikke er store variasjoner i plasseringen til den egenverdien plassert lengst til høyre. Alle scenarioene er godt dempet og har god respons. Den største forskjellen i egenverdier kommer i scenarioet med to ekstra sammenkoblede linjer i micronettet. Da er det en stor forflyttelse av egenverdien som er lengst til høyre mot y-aksen. Scenarioet der egenverdien lengst til høyre er lengst fra y-aksen er når to av energikildene er satt i samme node, og ikke fordelt på to forskjellige. Forslagene for å forbedre mikronettet til GridVille kan bli oppsummert i punktene: 1) Øke spenningen 2) En større energikilde er bedre enn to like store 3) Reduser antall noder. Basert på resultatene, er tendensen at mikronettet er mer stabilt nå det er simplere. For å oppnå dette, så kan batteriet or lastene bli plassert ut på mer enn bare en node, eller energikilder kan bli satt sammen. Det kan hende at den geografiske plasseringen av mikronettet ikke gjør dette mulig siden kanskje ikke solcelleanlegget og vindturbinen produserer maks ved samme plassering, eller at lasten bare kan bli plassert en plass i landsbyen. The objective of this thesis is to use small-signal analysis on the microgrid of GridVille, a student project trying to build a microgrid for a village in Nepal, to come with practical suggestions for improving the stability of the energy system. The practical suggestions that is mentioned are concretised by investigating changing the parameters voltage, droop gain, interconnecting lines and load distribution. To analyse the microgrid, the paper "Reduced-order model and stability analysis of low-voltage DC microgrid" by Sandeep Anand and Baylon G. Fernandes was used as the foundation. The model in the paper is recreated and a new model is developed for GridVille's microgrid with the same procedure as the paper. The line currents and source currents have the same response, expect for a difference in the time scaling for the paper recreation. For GridVille representation, the response follows similar patterns compared to the papers response and is therefore used for further analysis. The results generally show that there are not big variations in position of the rightmost eigenvalue. All the scenarios are stable and well damped. The biggest difference in eigenvalues comes from the scenario where two interconnecting lines are added to the microgrid. There is a significant movement of the rightmost eigenvalue towards the y-axis. The scenario with the rightmost eigenvalue the most to the left is where the scenario where two power sources are placed in one node, and not two different. The suggestions for improving the GridVille's microgrid is summed up in the points: 1) Increasing the voltage 2) One bigger power source is better than two equally big 3)~Reduce the number of nodes. Based on the results, it seems that the system is more stable when the microgrid is simpler. To achieve that, the Battery Energy Storage System (BESS) or loads can be placed on more than one node and power sources can be put together. However, due to the geographical location of the microgrid, this may not be possible if there solar photovoltaic (PV) array and wind turbine do not produce their maximum at the same location or that there only one place that the load can be placed.
- Published
- 2022
27. Gene Miller Interview, February 4, 2021
- Author
-
Beth Hodder, Kjell Petersen, Miller, Gene, Beth Hodder, Kjell Petersen, and Miller, Gene
- Abstract
Gene Miller describes growing up in Montana’s Swan Valley and how that helped him decide to become a U.S. Forest Service lookout. Miller talks about his 38-year tenure as a lookout, including on Priscilla Peak, three lookout towers as a relief staffer, and then 37 years on Blue Mountain. He tells about several fire incidents, including the inside phone melting after a lightning strike and igniting a fire under the lookout. He recalls a diverse range of visitors to the tower including Russian and Chinese delegations, pot smokers, an arsonist who was starting fires along the road, and the Hells Angels.
- Published
- 2021
28. Gene Miller Interview, February 26, 2021
- Author
-
Beth Hodder, Kjell Petersen, Miller, Gene, Beth Hodder, Kjell Petersen, and Miller, Gene
- Abstract
In this second interview, Gene Miller provides more information about growing up in the Swan Valley in the late 1930s and early 1940s. He describes the wildlife that lived in the area including bears and a young coyote who found Gene companionable. Miller tells more stories about his time as a U.S. Forest Service fire lookout, focusing on the wildlife there. He talks about visits from mountain goats and blue grouse, listening to elk bugling, and watching his dog chase pikas. Other wildlife incidents include finding evidence that a mule deer got its antlers caught in the ground wire for the lookout phone, feeding peanuts to Golden Mantled ground squirrels, picking huckleberries alongside a bear, and seeing wolf tracks. He also tells about a time when his dog refused to go home with a packer after Gene was helicoptered to the hospital with appendicitis.
- Published
- 2021
29. Bill Fordyce Interview, December 7, 2021
- Author
-
Beth Hodder, Kjell Petersen, Fordyce, William C., Beth Hodder, Kjell Petersen, and Fordyce, William C.
- Abstract
Bill Fordyce discusses being born in St. Louis and moving as a child to Sheridan, Wyoming where he lived on a dude ranch. He describes his family later moving back to St. Louis, but Bill couldn’t take city life and left after high school for the West. He said a friend in Helena, Montana suggesting he apply for a lookout job and was hired in 2009 for his first lookout job at Bearhat Lookout for the Lewis and Clark National Forest. He discusses being sent to work with no training, his first fire was one tree, and his season ending with the death of his mother. In 2010, back at Bearhat, Bill remembers reporting a mule breaking a woman’s knees. With a storm coming, a helicopter barely got her out. Bill’s most traumatic season was 2011 because he experienced responding to a death. The interview was stopped at this point because of technical difficulties. It was continued as OH 000-020 on December 9, 2021.
- Published
- 2021
30. Gene Miller Interview, March 4, 2021
- Author
-
Beth Hodder, Kjell Petersen, Miller, A. Eugene, Beth Hodder, Kjell Petersen, and Miller, A. Eugene
- Abstract
Gene Miller’s third interview follows his many years of fire experiences, from harrowing lightening strikes around and beneath his lookout that sparked fires to winds rocking the lookout, to large hail storms. He watched first from several lookouts during several years with many large fires, including a powerline fire that hit Patty Canyon, and a smokejumper whose joke to a firefighter resulted in an arson fire that burned Hellgate. He also experienced snowstorms and being evacuated from Diablo Lookout with a truck whose battery had died. He begins with stories from his childhood in the Swan Valley and 40 degree below zero weather.
- Published
- 2021
31. Bill Fordyce Interview, December 9, 2021
- Author
-
Beth Hodder, Kjell Petersen, Fordyce, William C., Beth Hodder, Kjell Petersen, and Fordyce, William C.
- Abstract
Bill recalls helping fly a dead man out in a helicopter near Beartop Lookout, his lookout site. He discusses lightning hitting Beartop and thinking he was deaf and blind for a while. He watches a grizzly bear stalk and elk, and talks of eating food eleven years past its expiration date because a grocery resupply didn’t come. Bill says he found a box in the attic that had held human ashes of a former lookout and letters from girls to another lookout. Bill discusses his next lookout, Scalplock, in Glacier National Park (2014-2016). Bill remembers Henry, the previous lookout, who took his own live after suffering from depression. Bill says Henry talked about “baking a potato,” which was keeping his feet in the oven to stay warm, a tradition Bill continued. In 2015, Bill recalls U.S. Highway 2 being closed because of a fire, and Scalplock was wrapped in fire wrap. While Scalplock was closed, Bill said he was sent to Cyclone Lookout in the North Fork Flathead, and experienced a wind that split a crossbeam on the tower. In 2017, Bill says he was the lookout at Numa Ridge in Glacier National Park. He talks of reporting many fires, including the Adair Ridge and Moose Creek fires, and the Sprague Creek Fire, which burned historic Sperry Chalet. He also said he had a choral group visit on the Fourth of July, singing songs, and kids from a math camp, whose teacher played an Indian flute. Bill says his next lookout job was at the Corral Hill Lookout, Nez Perce National Forest. There, he recalls a Hereford cow scratching on the tower and shaking it, and dry rot on catwalk boards. He talks of difficult topography for watching fires. He says his next job was at the Middle Fork Lookout, Salmon-Challis National Forest, where he had a long drive to a remote lookout, with water three miles away. Bill recalls few visitors but lots of fires with smokejumpers. He talks of a Chinook helicopter at the Jenny fire “making it rain.” He tells of a black bear visit to the catwalk at l:30 a.m
- Published
- 2021
32. Modelling a Hybrid Energy System with Micro Hydropower for a ZEB Fulfilling the FutureBuilt Standard
- Author
-
Synstad, Kjell Petersen, Ekren, Halvor Bratvold, Onsrud, Martin Wirak, Revheim, Pål Preede, Zimmermann, Pauline, and Burheim, Odne Stokke
- Abstract
For å oppnå 2-gradersmålet fra Parisavtalen, må byggenæringen kutte 60 % av sine CO2e-utslipp innen 2050, sammenlignet med nivået i 2012. Globalt står byggenæringen for omtrent 19 % av energirelaterte drivhusgassutslipp og i Norge kommer 40 % av energiforbruket fra bygninger. Nullutslippsbygninger (ZEB) kan være en del av løsningen for å oppnå målene om redusert utslipp. Målet for denne oppgaven er å undersøke forskjellige kombinasjoner av mikrovannkraftanlegg, solcellepanel og batterier for energisystemet på Skavanger skole. Oppgaven har et fokus på høy grad av selvforsynthet fra strømnettet og lave livsløpskostnader, samtidig som FutureBuilt kravet opprettholdes. FutureBuilt er en byggestandard som går over passivhusstandarden ved å kreve at bygget produserer en viss mengde elektrisitet i året. Energisystemet inkluderer et mikrovannkraftanlegg på 28 kW, noe som er uvanlig å benytte sammen med ZEB. Resultatene fra oppgaven kan bidra til økt kunnskap som kan brukes ved liknende prosjekter i fremtiden. Syv forskjellige scenarioer med ulike kombinasjoner av mikrovannkraftanlegg, solcelleareal og batterikapasitet ble laget, og en simuleringsmodell ble utviklet for å teste scenarioene. Simuleringen ble kjørt for alle scenarioene, der det ble sett på energibehov og produksjon fra solcellene, mens vannkraftverket ble regulert basert på gjenstående behov. Det ble også sett på energisystem bestående av kun solkraft og kun vannkraft. Energisystemet ble simulert med med en lav, middels og høy spotpris for å undersøke hvordan forskjellige strømpriser påvirker livsløpskostnadene. Resultater fra simuleringen inkluderer blant annet livsløpkostnader, selvforsynthet med og uten batteri og strømregningen for energisystemet. Dette er også visualisert i grafer for en gitt uke og over et helt år. Scenarioene med de mest gunstige resultatene var scenarioet med 28 kW vannkraft og 150 kWh batterykapasitet (Hydro-A), samt scenarioet med 600 m2 med solceller, 28 kW vannkraft og 75 kWh batterikapasitet (2-B). Disse scenarioene har høy selvforsynthet og relativt lave livsløpskostnader. Scenario Hydro-A har en selvforsynthet på 98.38 %, samt de laveste livsløpkostnadene av samtlige scenarioer. Hydro-A er ansett som det beste scenarioet dersom spotprisene ligger på et middels nivå. Scenario 2-B har en selvforsynthet på 97.94 % og har lavest livsløpkostnader dersom spotprisene er på det høyeste nivået. Scenarioet med høyest selvforsynthet er scenario 1-A. Dette scenarioet har 959 m2 med solceller, 150 kWh batterikapasitet og 28 kW vannkraft og når 99.48 % selvforsynthet, men har høyere livsløpkostnader enn de øvrige scenarioene. Det scenarioet som har dårligst selvforsynthet er scenario Original, som består av kun 959 m2 med solceller. Scenarioet har de høyeste livsløpkostnadene og en selvforsynthet på 32.37 %. To achieve the 2 °C goal set by the Paris Agreement, the global building and construction sector has to cut its CO2e emissions by 60 % in 2050 compared to the 2012 level. This sector accounts for approximately 19 % of energyrelated greenhouse gas emissions and in Norway, 40 % of the total energy usage comes from buildings. One solution that can help alleviate this challenge, is the increased investment in Zero Emission Buildings (ZEB). The objective of this thesis is to investigate different combinations of micro hydropower, solar power and batteries, to find a favourable energy system for Skavanger School. Self sufficiency, lifetime cost and fulfilling the FutureBuilt standard were the main focus areas for this energy system. FutureBuilt is a building standard where in addition to being a ZEB, the building has to produce a certain amount of electricity locally. Since the energy system at this school will include a micro hydropower plant of 28 kW, which is unusual for ZEBs, this thesis could provide results that could be useful for similiar projects in the future. Seven scenarios were created with different combinations of a hydropower plant, solar PV panels and battery capacity. A simulation was run for all scenarios, looking at power demand and solar power production, while regulating the hydropower production to fit the power demand for the school. In addition to this, scenarios with only solar PV panels, and only hydropower were simulated. The costs were calculated with a low, medium and high spot price to see the effect on lifetime costs when varying the electricity prices. Results produced from the simulation includes lifetime cost, self sufficiency with and without battery in addition to electricity bill, among others. In addition to this, several graphs showing weekly and yearly data from the results were created for the different scenarios. The scenarios that gave the most favourable results were the scenarios with a 28 kW hydropower plant and a 150 kWh battery (Hydro-A) in addition to the scenario with 600 m2 of solar PV panels, a 28 kW hydropower plant and a 75 kWh battery (2-B). These scenarios had a high self sufficiency, in addition to relatively low lifetime costs. Hydro-A has a self sufficiency of 98.38 % and has the lowest lifetime costs of all the scenarios assuming medium spot prices. Scenario 2-B has a self sufficiency of 97.94 % and has the lowest lifetime cost if the spot prices are higher. The scenario with 959 m2 of solar PV panels, 150 kWh of battery and hydropower (1-A) reaches a self sufficiency of 99.48 %, but comes with higher lifetime cost. The scenario with the worst performance was the one with only 959 m2 of solar PV panels (scenario Original), with a self sufficiency of 32.73 % and the highest lifetime cost.
- Published
- 2020
33. Common gene expression signatures in Parkinson’s disease are driven by changes in cell composition
- Author
-
Charalampos Tzoulis, Lilah Toker, Ole-Bjørn Tysnes, Inge Jonassen, Kristoffer Haugarvoll, Kjell Petersen, Fiona Dick, Guido Alves, and Gonzalo S. Nido
- Subjects
Cell type ,Parkinson's disease ,Parkinsonism ,Biology ,lcsh:RC346-429 ,Pathology and Forensic Medicine ,Transcriptome ,Pathogenesis ,Cellular and Molecular Neuroscience ,Lipid oxidation ,Medisinske Fag: 700 [VDP] ,Gene expression ,medicine ,Humans ,Neurodegeneration ,Prefrontal cortex ,lcsh:Neurology. Diseases of the nervous system ,Sequence Analysis, RNA ,Research ,Brain ,RNA ,Parkinson Disease ,RNA sequencing ,Ribosomal RNA ,medicine.disease ,Mitochondria ,Cell biology ,Unfolded protein response ,Neurology (clinical) - Abstract
BackgroundThe etiology of Parkinson’s disease (PD) is largely unknown. Genome-wide transcriptomic studies in bulk brain tissue have identified several molecular signatures associated with the disease. While these studies have the potential to shed light into the pathogenesis of PD, they are also limited by two major confounders: RNA post mortem degradation and heterogeneous cell type composition of bulk tissue samples. We performed RNA sequencing following ribosomal RNA depletion in the prefrontal cortex of 49 individuals from two independent case-control cohorts. Using cell-type specific markers, we estimated the cell-type composition for each sample and included this in our analysis models to compensate for the variation in cell-type proportions.ResultsRibosomal RNA depletion results in substantially more even transcript coverage, compared to poly(A) capture, in post mortem tissue. Moreover, we show that cell-type composition is a major confounder of differential gene expression analysis in the PD brain. Correcting for cell-type proportions attenuates numerous transcriptomic signatures that have been previously associated with PD, including vesicle trafficking, synaptic transmission, immune and mitochondrial function. Conversely, pathways related to endoplasmic reticulum, lipid oxidation and unfolded protein response are strengthened and surface as the top differential gene expression signatures in the PD prefrontal cortex.ConclusionsDifferential gene expression signatures in PD bulk brain tissue are significantly confounded by underlying differences in cell-type composition. Modeling cell-type heterogeneity is crucial in order to unveil transcriptomic signatures that represent regulatory changes in the PD brain and are, therefore, more likely to be associated with underlying disease mechanisms.
- Published
- 2019
34. Norwegian e-Infrastructure for Life Sciences (NeLS)
- Author
-
Christian Andreetta, Kjell Petersen, Eivind Hovig, Erik Hjerde, Kjetil Klepper, Morten Beck Rye, Jeevan Karloss Antony Samy, Finn Drabløs, Teshome Dagne Mulugeta, Dag Inge Våge, Wei Zhang, Matúš Kalaš, Abdulrahman Azab, Nils Peder Willassen, Lars Ailo Bongo, Inge Alexander Raknes, Inge Jonassen, Xiaxi Li, Ståle Nygård, Ghislain Fornous, Kidane M. Tekle, and Sveinung Gundersen
- Subjects
0301 basic medicine ,Service (systems architecture) ,VDP::Teknologi: 500::Informasjons- og kommunikasjonsteknologi: 550::Datateknologi: 551 ,VDP::Technology: 500::Information and communication technology: 550::Computer technology: 551 ,Interface (Java) ,Computer science ,federated authentication ,Information Storage and Retrieval ,Microservices ,General Biochemistry, Genetics and Molecular Biology ,Biological Science Disciplines ,World Wide Web ,integration API ,03 medical and health sciences ,microservices ,Data file ,VDP::Mathematics and natural science: 400::Zoology and botany: 480 ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Data management and sharing ,computer.programming_language ,General Immunology and Microbiology ,Application programming interface ,Information Dissemination ,Norway ,Secure Shell ,compute and storage infrastructure ,High-Throughput Nucleotide Sequencing ,General Medicine ,ELIXIR Norway ,Galaxy ,030104 developmental biology ,Workflow ,Database Management Systems ,Elixir (programming language) ,computer ,VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480 - Abstract
The Norwegian e-Infrastructure for Life Sciences (NeLS) has been developed by ELIXIR Norway to provide its users with a system enabling data storage, sharing, and analysis in a project-oriented fashion. The system is available through easy-to-use web interfaces, including the Galaxy workbench for data analysis and workflow execution. Users confident with a command-line interface and programming may also access it through Secure Shell (SSH) and application programming interfaces (APIs). NeLS has been in production since 2015, with training and support provided by the help desk of ELIXIR Norway. Through collaboration with NorSeq, the national consortium for high-throughput sequencing, an integrated service is offered so that sequencing data generated in a research project is provided to the involved researchers through NeLS. Sensitive data, such as individual genomic sequencing data, are handled using the TSD (Services for Sensitive Data) platform provided by Sigma2 and the University of Oslo. NeLS integrates national e-infrastructure storage and computing resources, and is also integrated with the SEEK platform in order to store large data files produced by experiments described in SEEK. In this article, we outline the architecture of NeLS and discuss possible directions for further development Copyright: © 2018 Tekle KM et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Published
- 2018
35. Transcriptome-wide mapping of signaling pathways and early immune responses in lumpfish leukocytes upon in vitro bacterial exposure
- Author
-
Anita Rønneseth, Charitra K Mishra, Gyri Teien Haugland, Håvard Øritsland Eggestøl, Kjell Petersen, Heidrun I. Wergeland, Harald S. Lunde, David Fredman, Tomasz Furmanek, and Duncan J. Colquhoun
- Subjects
0301 basic medicine ,Vibrio anguillarum ,Cell signaling ,Cyclopterus lumpus ,In silico ,animal diseases ,lcsh:Medicine ,Aquaculture ,Article ,Transcriptome ,03 medical and health sciences ,Fish Diseases ,Immune system ,Immunity ,Leukocytes ,Animals ,lcsh:Science ,Complement Activation ,Genetics ,Multidisciplinary ,biology ,Bacteria ,Base Sequence ,lcsh:R ,04 agricultural and veterinary sciences ,Bacterial Infections ,biology.organism_classification ,Immunity, Innate ,Complement system ,Perciformes ,030104 developmental biology ,Gene Expression Regulation ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,lcsh:Q - Abstract
We performed RNA sequencing, identified components of the immune system and mapped early immune responses of lumpfish (Cyclopterus lumpus) leukocytes following in vitro exposure to the pathogenic bacterium Vibrio anguillarum O1. This is the first characterization of immune molecules in lumpfish at the gene level. In silico analyses revealed that genes encoding proteins involved in pathogen recognition, cell signaling and cytokines in mammals and teleosts are conserved in lumpfish. Unique molecules were also identified. Pathogen recognition components include 13 TLRs, several NLRs and complement factors. Transcriptome-wide analyses of immune responses 6 and 24 hours post bacterial exposure revealed differential expression of 9033 and 15225 genes, respectively. These included TLR5S, IL-1β, IL-8, IL-6, TNFα, IL-17A/F3, IL-17C and several components of the complement system. The data generated will be valuable for comparative studies and make an important basis for further functional analyses of immune and pathogenicity mechanisms. Such knowledge is also important for design of immunoprophylactic measures in lumpfish, a species of fish now farmed intensively for use as cleaner-fish in Atlantic salmon (Salmo salar) aquaculture.
- Published
- 2018
36. Identification of highly connected and differentially expressed gene subnetworks in metastasizing endometrial cancer
- Author
-
Helga B. Salvesen, Anna Berg, Inge Jonassen, Elisabeth Wik, Karl-Henning Kalland, Henrica M.J. Werner, Mari K. Halle, Jone Trovik, Camilla Krakstad, Kjell Petersen, Karen Klepsland Mauland, Ingvild L. Tangen, Erling A. Hoivik, Kanthida Kusonmano, and Anne Margrete Øyan
- Subjects
0301 basic medicine ,Gene regulatory network ,Gene Expression ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Metastasis ,Basic Cancer Research ,Medicine and Health Sciences ,Gene Regulatory Networks ,Neoplasm Metastasis ,Hypoxia ,lcsh:Science ,Regulation of gene expression ,Multidisciplinary ,TCF4 ,Cell cycle ,Gene Expression Regulation, Neoplastic ,Oncology ,Physical Sciences ,Female ,Endometrial Carcinoma ,Network Analysis ,Research Article ,Computer and Information Sciences ,Epithelial-Mesenchymal Transition ,Permutation ,Context (language use) ,Computational biology ,Biology ,Carcinomas ,03 medical and health sciences ,Signs and Symptoms ,Uterine Cancer ,Diagnostic Medicine ,Genetics ,medicine ,Humans ,Gene ,Cell Proliferation ,Models, Statistical ,Discrete Mathematics ,Carcinoma ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,Computational Biology ,medicine.disease ,Endometrial Neoplasms ,030104 developmental biology ,HIF1A ,Metastatic Tumors ,Combinatorics ,Lesions ,RNA ,lcsh:Q ,Gynecological Tumors ,Mathematics ,Software - Abstract
We have identified nine highly connected and differentially expressed gene subnetworks between aggressive primary tumors and metastatic lesions in endometrial carcinomas. We implemented a novel pipeline combining gene set and network approaches, which here allows integration of protein-protein interactions and gene expression data. The resulting subnetworks are significantly associated with disease progression across tumor stages from complex atypical hyperplasia, primary tumors to metastatic lesions. The nine subnetworks include genes related to metastasizing features such as epithelial-mesenchymal transition (EMT), hypoxia and cell proliferation. TCF4 and TWIST2 were found as central genes in the subnetwork related to EMT. Two of the identified subnetworks display statistically significant association to patient survival, which were further supported by an independent validation in the data from The Cancer Genome Atlas data collection. The first subnetwork contains genes related to cell proliferation and cell cycle, while the second contains genes involved in hypoxia such as HIF1A and EGLN3. Our findings provide a promising context to elucidate the biological mechanisms of metastasis, suggest potential prognostic markers and further identify therapeutic targets. The pipeline R source code is freely available, including permutation tests to assess statistical significance of the identified subnetworks.
- Published
- 2018
37. Tumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenografts
- Author
-
Anne Margrete Øyan, Ercan Mutlu, Jian Wang, Oleg Tsinkalovsky, Linda Sleire, Xingang Li, Nicolas H.C. Brons, Tao Yan, Mireille Kayitesi Johannessen, Kjell Petersen, Siddharta S. Mitra, Hege Karine Jacobsen, Krishna M. Talasila, Mohummad Aminur Rahman, Hrvoje Miletic, Lina Leiss, Per Øyvind Enger, Karl-Henning Kalland, and Inge Jonassen
- Subjects
0301 basic medicine ,Cell type ,Pathology ,medicine.medical_specialty ,Cancer Research ,Stromal cell ,GFF-NOD/scid mice ,Stem cell markers ,Tumour-associated glial cells ,Mice, SCID ,Biology ,Stem cell marker ,Mice ,03 medical and health sciences ,Gene expression analysis ,SOX2 ,Mice, Inbred NOD ,Cell Line, Tumor ,Glioma ,Biomarkers, Tumor ,medicine ,Genetics ,Animals ,Humans ,Progenitor cell ,Brain Neoplasms ,Xenograft tumours ,Brain ,POU3F2 ,Nestin ,Microarray Analysis ,medicine.disease ,Immunohistochemistry ,Xenograft Model Antitumor Assays ,Cell biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Stem cell ,Transcriptome ,Glioblastoma ,Research Article ,Tumour-host interplay - Abstract
Background Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. Methods We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b+ immune and CD31+ endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors. This cell population was subsequently characterised using gene expression analyses and immunocytochemistry. Furthermore, sphere formation was assessed in vitro and their glioma growth-promoting ability was examined in vivo. Finally, the expression of TAG related markers was validated in human GBMs. Results TAGs were highly enriched for the expression of glial cell proteins including GFAP and myelin basic protein (MBP), and immature markers such as Nestin and O4. A fraction of TAGs displayed sphere formation in stem cell medium. Moreover, TAGs promoted brain tumour growth in vivo when co-implanted with glioma cells, compared to implanting only glioma cells, or glioma cells and unconditioned glial cells from mice without tumours. Genome-wide microarray analysis of TAGs showed an expression profile distinct from glial cells from healthy mice brains. Notably, TAGs upregulated genes associated with immature cell types and self-renewal, including Pou3f2 and Sox2. In addition, TAGs from highly angiogenic tumours showed upregulation of angiogenic factors, including Vegf and Angiopoietin 2. Immunohistochemistry of three GBMs, two patient biopsies and one GBM xenograft, confirmed that the expression of these genes was mainly confined to TAGs in the tumour bed. Furthermore, their expression profiles displayed a significant overlap with gene clusters defining prognostic subclasses of human GBMs. Conclusions Our data demonstrate that glial host cells in brain tumours are functionally distinct from glial cells of healthy mice brains. Furthermore, TAGs display a gene expression profile with enrichment for genes related to stem cells, immature cell types and developmental processes. Future studies are needed to delineate the biological mechanisms regulating the brain tumour-host interplay. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3109-8) contains supplementary material, which is available to authorized users.
- Published
- 2017
38. Hypomethylation of the CTCFL/BORIS promoter and aberrant expression during endometrial cancer progression suggests a role as an Epi-driver gene
- Author
-
Mari K. Halle, Martin Widschwendter, Camilla Krakstad, Henrica M.J. Werner, Kjell Petersen, Helga B. Salvesen, Anna Berg, Elisabeth Wik, Kanthida Kusonmano, Karl-Henning Kalland, Anne Margrete Øyan, Erling A. Hoivik, and Jone Trovik
- Subjects
recurrence ,Biology ,epi-driver gene ,Epigenesis, Genetic ,Metastasis ,Cell Line, Tumor ,medicine ,metastasis ,Humans ,RNA, Messenger ,Epigenetics ,Promoter Regions, Genetic ,Transcription factor ,Aged ,Oncogene ,Methylation ,DNA Methylation ,CTCF ,medicine.disease ,Endometrial Neoplasms ,DNA-Binding Proteins ,Oncology ,CTCFL/BORIS ,Mutation ,DNA methylation ,Disease Progression ,Cancer research ,Cancer/testis antigens ,Female ,Carcinoma, Endometrioid ,Research Paper ,Transcription Factors - Abstract
Cancers arise through accumulating genetic and epigenetic alterations, considered relevant for phenotype and approaches to targeting new therapies. We investigated a unique collection of endometrial cancer precursor samples and clinically annotated primary and metastatic lesions for two evolutionary and functionally related transcription factors, CCCTC-binding factor (zinc finger protein) (CTCF) and its paralogue CTCF-like factor, also denoted Brother of the Regulator of Imprinted Sites (CTCFL/BORIS). CTCF, a chromatin modeling- and transcription factor, is normally expressed in a ubiquitous fashion, while CTCFL/BORIS is restricted to the testis. In cancer, CTCF is thought to be a tumor suppressor, while CTCFL/BORIS has been suggested as an oncogene. CTCF mutations were identified in 13 %, with CTCF hotspot frameshift mutations at p.T204, all observed solely in the endometrioid subtype, but with no association with outcome. Interestingly, CTCFL/BORIS was amongst the top ranked genes differentially expressed between endometrioid and non-endometrioid tumors, and increasing mRNA level of CTCFL/BORIS was highly significantly associated with poor survival. As aberrant CTCFL/BORIS expression might relate to loss of methylation, we explored methylation status in clinical samples from complex atypical hyperplasia, through primary tumors to metastatic lesions, demonstrating a pattern of DNA methylation loss during disease development and progression in line with the increase in CTCFL/BORIS mRNA expression observed. Thus, CTCF and CTCFL/BORIS are found to diverge in the different subtypes of endometrial cancer, with CTCFL/BORIS activation through demethylation from precursors to metastatic lesions. We thus propose, CTCFL/BORIS as an Epi-driver gene in endometrial cancer, suggesting a potential for future vaccine development.
- Published
- 2014
39. Pipelined data‐flow delegated orchestration for data‐intensive eScience workflows
- Author
-
Paweł Sztromwasser, Pål Puntervoll, Sattanathan Subramanian, and Kjell Petersen
- Subjects
Database ,Delegation ,Computer Networks and Communications ,Computer science ,SOAP ,computer.internet_protocol ,business.industry ,Data management ,media_common.quotation_subject ,computer.software_genre ,Data flow diagram ,XML Schema (W3C) ,Workflow ,Orchestration (computing) ,Web service ,business ,Software engineering ,computer ,Information Systems ,media_common - Abstract
PurposeeScience workflows use orchestration for integrating and coordinating distributed and heterogeneous scientific resources, which are increasingly exposed as web services. The rate of growth of scientific data makes eScience workflows data‐intensive, challenging existing workflow solutions. Efficient methods of handling large data in scientific workflows based on web services are needed. The purpse of this paper is to address this issue.Design/methodology/approachIn a previous paper the authors proposed Data‐Flow Delegation (DFD) as a means to optimize orchestrated workflow performance, focusing on SOAP web services. To improve the performance further, they propose pipelined data‐flow delegation (PDFD) for web service‐based eScience workflows in this paper, by leveraging from the domain of parallel programming. Briefly, PDFD allows partitioning of large datasets into independent subsets that can be communicated in a pipelined manner.FindingsThe results show that the PDFD improves the execution time of the workflow considerably and is capable of handling much larger data than the non‐pipelined approach.Practical implicationsExecution of a web service‐based workflow hampered by the size of data can be facilitated or improved by using services supporting Pipelined Data‐Flow Delegation.Originality/valueContributions of this work include the proposed concept of combining pipelining and Data‐Flow Delegation, an XML Schema supporting the PDFD communication between services, and the practical evaluation of the PDFD approach.
- Published
- 2013
40. RareVariantVis: new tool for visualization of causative variants in rare monogenic disorders using whole genome sequencing data
- Author
-
Paweł Sztromwasser, Alexander Hoischen, Tomasz Stokowy, Christian Gilissen, Gunnar Houge, Torunn Fiskerstrand, Rita Holdhus, Inge Jonassen, Kjell Petersen, Kornel Labun, Vidar M. Steen, and Mateusz Garbulowski
- Subjects
0301 basic medicine ,Statistics and Probability ,dbSNP ,Sequence analysis ,Biology ,Biochemistry ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Rare Diseases ,Genetic variation ,Humans ,Exome ,Molecular Biology ,Genetics ,Whole genome sequencing ,030219 obstetrics & reproductive medicine ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Genome, Human ,Inheritance (genetic algorithm) ,Genetic Variation ,Sequence Analysis, DNA ,Computer Science Applications ,Visualization ,Computational Mathematics ,030104 developmental biology ,Computational Theory and Mathematics - Abstract
Motivation: The search for causative genetic variants in rare diseases of presumed monogenic inheritance has been boosted by the implementation of whole exome (WES) and whole genome (WGS) sequencing. In many cases, WGS seems to be superior to WES, but the analysis and visualization of the vast amounts of data is demanding. Results: To aid this challenge, we have developed a new tool—RareVariantVis—for analysis of genome sequence data (including non-coding regions) for both germ line and somatic variants. It visualizes variants along their respective chromosomes, providing information about exact chromosomal position, zygosity and frequency, with point-and-click information regarding dbSNP IDs, gene association and variant inheritance. Rare variants as well as de novo variants can be flagged in different colors. We show the performance of the RareVariantVis tool in the Genome in a Bottle WGS data set. Availability and implementation: https://www.bioconductor.org/packages/3.3/bioc/html/RareVariantVis.html Contact: tomasz.stokowy@k2.uib.no Supplementary information: Supplementary data are available at Bioinformatics online.
- Published
- 2016
41. KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer
- Author
-
Camilla Krakstad, Kjell Petersen, Frederik Holst, Anne Margrete Øyan, Lars A. Akslen, Ronald Simon, Siv Mjøs, Elisabeth Wik, Kanthida Kusonmano, Karl-Henning Kalland, Even Birkeland, Erling A. Hoivik, Helga B. Salvesen, Maria B. Ræder, Henrica M.J. Werner, and Jone Trovik
- Subjects
Adult ,Cancer Research ,Gene Dosage ,amplification ,Biology ,Genetics & Genomics ,medicine.disease_cause ,Polymerase Chain Reaction ,Proto-Oncogene Proteins p21(ras) ,Predictive Value of Tests ,Proto-Oncogene Proteins ,Gene duplication ,KRAS ,medicine ,Carcinoma ,Humans ,Clinical significance ,neoplasms ,KRAS Gene Amplification ,Aged ,Oligonucleotide Array Sequence Analysis ,Endometrial cancer ,Gene Amplification ,Sequence Analysis, DNA ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Endometrial Neoplasms ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Genes, ras ,Phenotype ,Oncology ,Tissue Array Analysis ,Lymphatic Metastasis ,Mutation ,endometrial cancer ,ras Proteins ,Cancer research ,Female ,Neoplasm Grading ,Carcinogenesis - Abstract
Background: Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas. Methods: We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally. Results: Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high International Federation of Gynaecology and Obstetrics stage, non-endometrioid subtype, high grade, aneuploidy, receptor loss and high KRAS mRNA levels, also found to be associated with aggressive phenotype. In contrast, KRAS mutations were present in 14.7% of primary lesions with no increase in metastatic lesions, and did not influence outcome, but was significantly associated with endometrioid subtype, low grade and obesity. Conclusion: These results support that KRAS amplification and KRAS mRNA expression, both increasing from primary to metastatic lesions, are relevant for endometrial carcinoma disease progression.
- Published
- 2012
42. Expression profile of heat shock proteins in acute myeloid leukaemia patients reveals a distinct signature strongly associated with FLT3 mutation status - consequences and potentials for pharmacological intervention
- Author
-
Håkon Reikvam, Kjell Petersen, Kimberley Joanne Hatfield, Bjørn Tore Gjertsen, Randi Hovland, Jørn Skavland, Øystein Bruserud, and Elisabeth Ersvær
- Subjects
Myeloid ,biology ,Angiogenesis ,medicine.medical_treatment ,hemic and immune systems ,Hematology ,Hsp90 ,Hsp90 inhibitor ,Hsp70 ,Cytokine ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Heat shock protein ,medicine ,Cancer research ,biology.protein ,Interleukin 8 - Abstract
Heat shock proteins (HSPs) are molecular chaperones that assist proteins in their folding to native structures. HSPs are regarded as possible therapeutic targets in acute myeloid leukaemia (AML). We used bioinformatical approaches to characterize the HSP profile in AML cells from 75 consecutive patients, in addition to the effect of the HSP90 inhibitor 17-DMAG. Patients harbouring a FLT3-internal tandem duplication (FLT3-ITD) were extensively overrepresented in the cluster with high HSP levels, indicating a strong dependence of HSPs in stabilizing FLT3-ITD encoded oncoproteins. FLT3 ligation further increased the levels of HSP90 and its co-chaperone HSP70. HSP90 inhibition had a stronger pro-apoptotic effect for AML cells with FLT3-ITD than for cells with wild-type FLT3, whereas the anti-proliferative effect of HSP90 inhibition was similar for the two patient subsets. HSP90 inhibition altered the constitutive cytokine release profile in an anti-angiogenic direction independent of FLT3 mutational status: (i) pro-angiogenic CXCL8, MMP-2 and MMP-9 showed a stronger decrease than anti-angiogenic CXCL9-11, (ii) the Tie-2 agonist Ang-1 showed a stronger decrease than the potentially antagonistic Ang-2, and (iii) VEGF and HGF levels were decreased. Finally, HSP90 inhibition counteracted the leukaemia-stimulating effect of endothelial cells. Our studies demonstrate that HSP90 inhibition mediates anti-leukaemic effects through both direct and indirect activity.
- Published
- 2011
43. Hepatic in vitro toxicity assessment of PBDE congeners BDE47, BDE153 and BDE154 in Atlantic salmon (Salmo salar L.)
- Author
-
Liv Søfteland, Terence Wu, Pål A. Olsvik, Anne-Kristin Stavrum, and Kjell Petersen
- Subjects
Fish Proteins ,Male ,endocrine system ,Proteome ,Microarray ,Health, Toxicology and Mutagenesis ,Polybrominated Biphenyls ,Salmo salar ,Protein Array Analysis ,In Vitro Techniques ,Aquatic Science ,Real-Time Polymerase Chain Reaction ,Transcriptome ,Halogenated Diphenyl Ethers ,Animals ,Glucose homeostasis ,Electrophoresis, Gel, Two-Dimensional ,Salmo ,Toxicity Tests, Chronic ,reproductive and urinary physiology ,Flame Retardants ,biology ,Gene Expression Profiling ,biology.organism_classification ,Congener ,Biochemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Environmental chemistry ,Toxicity ,Brominated flame retardant ,Hepatocytes ,Regression Analysis ,Toxicogenomics ,Water Pollutants, Chemical - Abstract
The brominated flame retardant congeners BDE47, BDE153 and BDE154 are among the congeners accumulating to the highest degree in fish. In order to gain knowledge about the toxicological effects of PBDEs in fish, microarray-based transcriptomic and 2D-DIGE/MALDI-TOF/TOF proteomic approaches were used to screen for effects in primary Atlantic salmon hepatocytes exposed to these congeners alone or in combination (PBDE-MIX). A small set of stress related transcripts and proteins were differentially expressed in the PBDE exposed hepatocytes. The PBDE-MIX, and BDE153 to a lesser degree, seems to have induced metabolic disturbances by affecting several pathways related to glucose homeostasis. Further, effects on cell cycle control and proliferation signal pathways in PBDE-MIX-exposed hepatocytes clearly suggest that the PBDE exposure affected cell proliferation processes. CYP1A was 7.41- and 7.37-fold up-regulated in hepatocytes exposed to BDE47 and PBDE-MIX, respectively, and was the only biotransformation pathway affected by the PBDE exposure. The factorial design and PLS regression analyses of the effect of the PBDE-MIX indicated that BDE47 contributed the most to the observed CYP1A response, suggesting that this congener should be incorporated in the toxic equivalent (TEQ) concept in future risk assessment of dioxin-like chemicals. Additionally, a significant up-regulation of the ER-responsive genes VTG and ZP3 was observed in cells exposed to BDE47 and PBDE-MIX. Further analyses suggested that BDE47 and BDE154 have an estrogenic effect in male fish. The data also suggested an antagonistic interaction between BDE153 and BDE154. In conclusion, this study shows that PBDEs can affect several biological systems in Atlantic salmon cells, and demonstrates the need for more studies on the simultaneous exposure to chemical mixtures to identify combined effects of chemicals.
- Published
- 2011
44. Data partitioning enables the use of standard SOAP Web Services in genome-scale workflows
- Author
-
Paweł Sztromwasser, Kjell Petersen, and Pál Puntervoll
- Subjects
Internet ,User-Computer Interface ,Genome ,Databases, Factual ,Databases, Genetic ,Data processing, computer science, computer systems ,Genomics ,General Medicine ,TP248.13-248.65 ,Software ,Biotechnology ,Workflow - Abstract
Summary Biological databases and computational biology tools are provided by research groups around the world, and made accessible on the Web. Combining these resources is a common practice in bioinformatics, but integration of heterogeneous and often distributed tools and datasets can be challenging. To date, this challenge has been commonly addressed in a pragmatic way, by tedious and error-prone scripting. Recently however a more reliable technique has been identified and proposed as the platform that would tie together bioinformatics resources, namely Web Services. In the last decade the Web Services have spread wide in bioinformatics, and earned the title of recommended technology. However, in the era of high-throughput experimentation, a major concern regarding Web Services is their ability to handle large-scale data traffic. We propose a stream-like communication pattern for standard SOAP Web Services, that enables efficient flow of large data traffic between a workflow orchestrator and Web Services. We evaluated the data-partitioning strategy by comparing it with typical communication patterns on an example pipeline for genomic sequence annotation. The results show that data-partitioning lowers resource demands of services and increases their throughput, which in consequence allows to execute in-silico experiments on genome-scale, using standard SOAP Web Services and workflows. As a proof-of-principle we annotated an RNA-seq dataset using a plain BPEL workflow engine.
- Published
- 2011
45. A prospective observational study of the effect of platelet transfusions on levels of platelet-derived cytokines, chemokines and interleukins in acute leukaemia patients with severe chemotherapy-induced cytopenia
- Author
-
Håkon Reikvam, Kjell Petersen, Øystein Bruserud, Tor Hervig, Tore Wentzel-Larsen, and Torunn Oveland Apelseth
- Subjects
Adult ,Blood Platelets ,Male ,Chemokine ,Pancytopenia ,medicine.medical_treatment ,Clinical Biochemistry ,Immunology ,Platelet Transfusion ,Young Adult ,chemistry.chemical_compound ,Humans ,Immunology and Allergy ,Medicine ,Platelet ,Prospective Studies ,Mean platelet volume ,Cytopenia ,Leukemia ,biology ,business.industry ,Interleukins ,Growth factor ,Interleukin ,Middle Aged ,medicine.disease ,Vascular endothelial growth factor ,Platelet transfusion ,chemistry ,Case-Control Studies ,biology.protein ,Female ,Chemokines ,business - Abstract
Platelet concentrates contain soluble mediators derived from both platelets and contaminating leukocytes. During platelet transfusion these mediators are transferred, and transfusion-induced modulation of the cytokine network may then occur, possibly contributing to transfusion reactions, immunomodulation, or affecting residual leukemic cells. In this prospective observational study, we investigate the effect of platelet transfusion on the systemic levels of platelet-derived cytokines, chemokines and interleukins in an unselected group of acute leukaemia patients with severe chemotherapy-induced cytopenia. We investigated 31 platelet transfusions involving pre-storage, white blood cell-reduced, gamma-irradiated or pathogen-inactivated, photochemically-treated platelet concentrates received by 10 unselected patients. Peripheral blood plasma samples were collected before, immediately after, one hour, and 24 hours after the transfusions. Sampling from platelet concentrates was performed immediately before transfusion. A total of 31 soluble mediators were examined. Ten healthy controls matched for age and gender were included. Despite heterogeneity in patients and platelet concentrates, significantly increased plasma concentrations were detected for the platelet-derived mediators, platelet-derived growth factor, β-thromboglobulin, transforming growth factor-β (TGF-β), CCL5, and CXCL4, 1 hour and/or immediately after platelet transfusions. The plasma levels of vascular endothelial growth factor and soluble CD40 ligand were not altered by platelet transfusion. Certain interleukins (IL-1β, IL-2, IL-4, IL-6, IL-9, and IL-12), as well as interferon-γ showed a minor, transient decrease in systemic plasma levels during the first hour following transfusion. Platelet transfusions modulate the systemic cytokine network in acute leukaemia patients with severe, chemotherapy-induced cytopenia.
- Published
- 2011
46. Hyperoxia retards growth and induces apoptosis, changes in vascular density and gene expression in transplanted gliomas in nude rats
- Author
-
Per Øystein Sakariassen, Linda Elin Birkhaug Stuhr, Kjell Petersen, Anne Margrete Øyan, Rolf Bjerkvig, Karl-Henning Kalland, Rolf K. Reed, and Anette Raa
- Subjects
Male ,Cancer Research ,Programmed cell death ,Angiogenesis ,Apoptosis ,Hyperoxia ,Biology ,Random Allocation ,Rats, Nude ,Glioma ,medicine ,Animals ,RNA, Neoplasm ,Hyperbaric Oxygenation ,TUNEL assay ,Neovascularization, Pathologic ,Brain Neoplasms ,Cell growth ,Gene Expression Profiling ,Neoplasms, Experimental ,medicine.disease ,Molecular biology ,Rats ,Gene Expression Regulation, Neoplastic ,Oxygen ,Neurology ,Oncology ,Female ,Neurology (clinical) ,medicine.symptom ,Immunostaining - Abstract
This study describes the biological effects of hyperoxic treatment on BT4C rat glioma xenografts in vivo with special reference to tumor growth, angiogenesis, apoptosis, general morphology and gene expression parameters. One group of tumor bearing animals was exposed to normobaric hyperoxia (1 bar, pO(2) = 1.0) and another group was exposed to hyperbaric hyperoxia (2 bar, pO(2) = 2.0), whereas animals housed under normal atmosphere (1 bar, pO(2) = 0.2) served as controls. All treatments were performed at day 1, 4 and 7 for 90 min. Treatment effects were determined by assessment of tumor growth, vascular morphology (immunostaining for von Willebrand factor), apoptosis by TUNEL staining and cell proliferation by Ki67 staining. Moreover, gene expression profiles were obtained and verified by real time quantitative PCR. Hyperoxic treatment caused a approximately 60% reduction in tumor growth compared to the control group after 9 days (p < 0.01). Light microscopy showed that the tumors exposed to hyperoxia contained large "empty spaces" within the tumor mass. Moreover, hyperoxia induced a significant increase in the fraction of apoptotic cells ( approximately 21%), with no significant change in cell proliferation. After 2 bar treatment, the mean vascular density was reduced in the central parts of the tumors compared to the control and 1 bar group. The vessel diameters were significantly reduced (11-24%) in both parts of the tumor tissue. Evidence of induced cell death and reduced angiogenesis was reflected by gene expression analyses.Increased pO(2)-levels in experimental gliomas, using normobaric and moderate hyperbaric oxygen therapy, caused a significant reduction in tumor growth. This process is characterized by enhanced cell death, reduced vascular density and changes in gene expression corresponding to these effects.
- Published
- 2007
47. BMET-34DRUG REPURPOSING DISCOVERS BETA-SITOSTEROL AS AN EFFECTIVE THERAPEUTIC AGENT AGAINST MELANOMA BRAIN METASTASES IN VIVO
- Author
-
Sarah Tam, Kai Ove Skaftnesmo, Karl Johan Tronstad, Lars Prestegarden, Jobin K. Varughese, Kjell Petersen, Frits Thorsen, Clifford G. Tepper, Terje Sundstrøm, Morten Lund-Johansen, Gro V. Røsland, Francisco Azuaje, Elizabeth S. Ingham, Rolf Bjerkvig, Lisa Even, and Katherine W. Ferrara
- Subjects
MAPK/ERK pathway ,Cancer Research ,business.industry ,Melanoma ,Pharmacology ,Gene signature ,medicine.disease ,Mediator ,Oncology ,In vivo ,Gene expression ,Medicine ,Neurology (clinical) ,business ,Gene ,Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology ,Brain metastasis - Abstract
Despite major therapeutic advances in the management of patients with metastatic melanoma, brain metastases remain an intractable problem. It has proven difficult to identify and target single genes or pathways critical to brain metastasis formation. Here, we explore a more global and preventive treatment approach to melanoma brain metastases within an established xenograft model of human melanoma. Mice were injected intracardially and followed for six weeks with whole-body BLI and brain MRI. Tumor-bearing brains, adrenals, ovaries, and femurs were harvested and enzymatically dissociated before three tumor cell samples from each organ were flow-sorted and subjected to RNA sequencing. We were able to define a 108-gene brain metastasis gene signature, and queried the Connectivity Map database for candidate drugs, i.e. drugs that induce an opposite gene expression profile in various cancer cell lines. We found the cholesterol analogue beta-sitosterol to effectively inhibit brain metastases and improve survival, both in established and preventive therapeutic settings. Beta-sitosterol extensively suppressed the MAPK pathway, and effectively reduced mitochondrial respiration through Complex I inhibition. This novel mechanistic synergy may open new avenues of systemic therapy against metastatic melanoma, as increased mitochondrial respiration is a key mediator of resistance to MAPK-targeted drugs.
- Published
- 2015
48. Distributed and interactive visual analysis of omics data
- Author
-
Frode S. Berven, Kjell Petersen, Inge Jonassen, Harald Barsnes, and Yehia Farag
- Subjects
Web browser ,Proteome ,Computer science ,Download ,Molecular Sequence Data ,Biophysics ,Omics ,Biochemistry ,Omics data ,World Wide Web ,Systems Integration ,User-Computer Interface ,Interactivity ,Interactive visual analysis ,Sequence Analysis, Protein ,Web page ,Data Mining ,Database Management Systems ,Computational analysis ,Amino Acid Sequence ,Databases, Protein ,Social Media ,Software - Abstract
The amount of publicly shared proteomics data has grown exponentially over the last decade as the solutions for sharing and storing the data have improved. However, the use of the data is often limited by the manner of which it is made available. There are two main approaches: download and inspect the proteomics data locally, or interact with the data via one or more web pages. The first is limited by having to download the data and thus requires local computational skills and resources, while the latter most often is limited in terms of interactivity and the analysis options available. A solution is to develop web-based systems supporting distributed and fully interactive visual analysis of proteomics data. The use of a distributed architecture makes it possible to perform the computational analysis at the server, while the results of the analysis can be displayed via a web browser without the need to download the whole dataset. Here the challenges related to developing such systems for omics data will be discussed. Especially how this allows for multiple connected interactive visual displays of omics dataset in a web-based setting, and the benefits this provide for computational analysis of proteomics data.This article is part of a Special Issue entitled: Computational Proteomics.
- Published
- 2015
49. Syndromic X-linked intellectual disability segregating with a missense variant in RLIM
- Author
-
Torunn Fiskerstrand, Rita Holdhus, Han G. Brunner, Elin Tønne, Asbjørg Stray-Pedersen, Kjell Petersen, Alexander Hoischen, Christian Gilissen, Christine Stansberg, Vidar M. Steen, and Trine Prescott
- Subjects
Adult ,Male ,X-linked intellectual disability ,Ubiquitin-Protein Ligases ,Molecular Sequence Data ,Mutation, Missense ,Biology ,Article ,X-inactivation ,symbols.namesake ,Genetics ,medicine ,Humans ,Missense mutation ,Amino Acid Sequence ,Child ,Gene ,Genetics (clinical) ,X chromosome ,Exome sequencing ,Aged ,Sanger sequencing ,Zinc finger ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Base Sequence ,Infant ,Middle Aged ,medicine.disease ,Child, Preschool ,Mental Retardation, X-Linked ,symbols ,Female - Abstract
Contains fulltext : 152770.pdf (Publisher’s version ) (Open Access) We describe a three-generation Norwegian family with a novel X-linked intellectual disability (XLID) syndrome characterized by subtle facial dysmorphism, autism and severe feeding problems. By exome sequencing we detected a rare missense variant (c.1067A>G, p.(Tyr356Cys)) in the RLIM gene, in two affected male second cousins. Sanger sequencing confirmed the presence of the variant in the four affected males (none of whom were siblings) and in three mothers available for testing. The variant was not present in 100 normal Norwegian controls, has not been reported in variant databases and is deleterious according to in silico prediction tools. The clinical phenotype and the variant co-segregate, yielding a LOD score of 3.0 for linkage to the shared region (36.09 Mb), which contains 242 genes. No other shared rare variants on the X chromosome were detected in the two affected exome-sequenced individuals, and all female carriers had an extremely skewed X-chromosome inactivation pattern. RLIM encodes RING zinc finger protein 12 (RNF12), an ubiquitin ligase that is essential for X inactivation in mice and that acts as a co-regulator of a range of transcription factors, particularly those containing a LIM homeodomain. Tyrosine in position 356 in RNF12 is located within a highly conserved domain essential for binding such transcription factors. Expression of RNF12 is widespread during embryogenesis, and is particularly high in the outer layers of the cerebral cortex. Functional studies are needed to prove a definite causal relationship between the variant and the phenotype. Subsequent reports may confirm a role for RLIM variants in patients with XLID.
- Published
- 2015
50. Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects
- Author
-
Inge Jonassen, Kjell Petersen, Roland Jonsson, Anne Isine Bolstad, and Trond Ove R. Hjelmervik
- Subjects
Adult ,Male ,Saliva ,Microarray ,Immunology ,Major histocompatibility complex ,Salivary Glands ,Rheumatology ,Complementary DNA ,Gene expression ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,CXCL13 ,Gene ,Aged ,Aged, 80 and over ,biology ,Gene Expression Profiling ,Middle Aged ,Gene expression profiling ,Sjogren's Syndrome ,Case-Control Studies ,biology.protein ,Female - Abstract
Objective To identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). Methods A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase–polymerase chain reaction techniques. Results We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in ≥90% of primary SS patients and in ≤10% of the controls. Lymphotoxin β, as well as a number of major histocompatibility complex genes, cytokines, and lymphocyte activation factors, manifested its role in the pathogenesis of SS. Numerous type I interferon genes related to virus infection were found among the top 200 genes, with increased expression in primary SS. Interestingly, the expression of carbonic anhydrase II, which is essential in saliva production and secretion, and the apoptosis regulator Bcl-2–like 2 were down-regulated in primary SS patients. Conclusion We have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up-regulated or down-regulated during disease, constituting an excellent platform for forthcoming functional studies.
- Published
- 2005
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.