Recent publications from the former Biotechnology Centre of Oslo

• Martîn, Ruth Martîn; Portantier, Marina; Chica-Balaguera, Nathalia; Nyquist-Andersen, Mari; Mata, J & Lopez-Aviles, Sandra (2017). A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast. Current Biology. ISSN 0960-9822. 27(2), p. 175–188. doi: 10.1016/j.cub.2016.11.037. Full text in Research Archive Show summary

  Extracellular cues regulate cell fate, and this is mainly achieved through the engagement of specific transcriptional programs. The TORC1 and TORC2 complexes mediate the integration of nutritional cues to cellular behavior, but their interplay is poorly understood. Here, we use fission yeast to investigate how phosphatase activity participates in this interplay during the switch from proliferation to sexual differentiation. We find that loss of PP2A-B55Pab1 enhances the expression of differentiation-specific genes and leads to premature conjugation. pab1 deletion brings about a transcriptional profile similar to TORC1 inactivation, and deletion of pab1 overcomes the repression of differentiation genes in cells overexpressing TORC1. Importantly, we show that this effect is mediated by an increased TORC2-AKT (Gad8) signaling. Under nutrient-rich conditions, PP2A-B55Pab1 dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55Pab1 through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55Pab1 enables a crosstalk between the two TOR complexes that controls cell-fate decisions in response to nutrient availability.

• Dukic, Aleksandra; McClymont, David & Tasken, Kjetil (2017). A Cell-Based High-Throughput Assay for Gap Junction Communication Suitable for Assessing Connexin 43-Ezrin Interaction Disruptors Using IncuCyte ZOOM. Journal of Biomolecular Screening. ISSN 1087-0571. 22(1), p. 77–85. doi: 10.1177/1087057116669120. Full text in Research Archive Show summary

  Connexin 43 (Cx43), the predominant gap junction (GJ) protein, directly interacts with the A-kinase-anchoring protein (AKAP) Ezrin in human cytotrophoblasts and a rat liver epithelial cells (IAR20). The Cx43-Ezrin–protein kinase (PKA) complex facilitates Cx43 phosphorylation by PKA, which triggers GJ opening in cytotrophoblasts and IAR20 cells and may be a general mechanism regulating GJ intercellular communication (GJIC). Considering the importance of Cx43 GJs in health and disease, they are considered potential pharmaceutical targets. The Cx43-Ezrin interaction is a protein-protein interaction that opens possibilities for targeting with peptides and small molecules. For this reason, we developed a high-throughput cell-based assay in which GJIC can be assessed and new compounds characterized. We used two pools of IAR20 cells, calcein loaded and unloaded, that were mixed and allowed to attach. Next, GJIC was monitored over time using automated imaging via the IncuCyte imager. The assay was validated using known GJ inhibitors and anchoring peptide disruptors, and we further tested new peptides that interfered with the Cx43-Ezrin binding region and reduced GJIC. Although an AlphaScreen assay can be used to screen for Cx43-Ezrin interaction inhibitors, the cell-based assay described is an ideal secondary screen for promising small-molecule hits to help identify the most potent compounds. © 2017 SAGE Publications

• Moltu, Kristine; Henjum, Karen; Oberprieler, Nikolaus; Bjørnbeth, Bjørn Atle & Tasken, Kjetil (2017). Proximal signaling responses in peripheral T cells from colorectal cancer patients are affected by high concentrations of circulating prostaglandin E2. Human Immunology. ISSN 0198-8859. 78(2), p. 129–137. doi: 10.1016/j.humimm.2016.10.007. Full text in Research Archive Show summary

  Patients with colorectal cancer (CRC) have been shown to have elevated levels of circulating prostaglandin E2 (PGE2) which promotes cancer progression and suppresses T cell immune responses. In this study we evaluated whether signaling responses in T lymphocytes obtained from peripheral blood of CRC patients were affected by the sustained exposure to increased levels of PGE2. The phosphorylation status of an extended panel of proteins involved in downstream signaling cascades in T cells was profiled at a single cell level both in naïve and antigen-experienced cells after triggering T cell-, prostaglandin- and interleukin-2 receptors. Peripheral T cells from patients with elevated PGE2 levels displayed aberrant T cell signaling responses downstream of the T cell receptor (assessed by reduced phosphorylation of CD3ζ and SLP76), and after triggering the IL-2 receptor (assessed by reduced phosphorylation of STAT5) when compared to T cells from CRC patients with lower levels of PGE2 and T cells from healthy blood donors. This signaling study of circulating T cells from CRC patients indicates that increased systemic PGE2 levels affect proximal T cell responses and confirms phospho-specific flow cytometry to be a valuable tool for revealing signaling signatures in immunological disorders.

• Landsverk, Ole J. B.; Snir, Omri; Casado, Raquel Bartolome; Richter, Lisa Maria; Mold, Jeff E. & Réu, Pedro [Show all 18 contributors for this article] (2017). Antibody-secreting plasma cells persist for decades in human intestine. Journal of Experimental Medicine (JEM). ISSN 0022-1007. 214(2), p. 309–317. doi: 10.1084/jem.20161590. Full text in Research Archive Show summary

  Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19+ PC subset was dynamically exchanged, whereas of two CD19− PC subsets, CD45+ PCs exhibited little and CD45− PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45− PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19− PC subsets support selection and maintenance of protective PCs for life in human intestine.

• Gunasekaran, Stalin Chellappa; Hugenschmidt, Harald; Hagness, Morten; Subramani, Saranya; Melum, Espen & Line, Pål Dag [Show all 10 contributors for this article] (2017). CD8+ T cells that coexpress ROR?t and T-bet are functionally impaired and expand in patients with distal bile duct cancer. Journal of Immunology. ISSN 0022-1767. 198(4), p. 1729–1739. doi: 10.4049/jimmunol.1600061. Full text in Research Archive
• Dorfman, Mauricio D; Krull, Jordan E; Scarlett, Jarrad M; Guyenet, Stephan J; Sajan, Mini P. & Damian, Vincent [Show all 12 contributors for this article] (2017). Deletion of Protein Kinase C λ in POMC Neurons Predisposes to Diet-Induced Obesity. Diabetes. ISSN 0012-1797. 66(4), p. 920–934. doi: 10.2337/db16-0482. Full text in Research Archive
• Ghatak, Sushmita; Niland, Stephan; Schulz, Jan-Niklas; Wang, Fang; Eble, Johannes A. & Leitges, Michael [Show all 10 contributors for this article] (2016). Role of Integrins α1β1 and α2β1 in Wound and Tumor Angiogenesis in Mice. American Journal of Pathology. ISSN 0002-9440. 186(11), p. 3011–3027. doi: 10.1016/j.ajpath.2016.06.021. Full text in Research Archive
• Raj, Deepak Balaji Thimiri Govinda & Khan, Niamat Ali (2016). Designer nanoparticle: Nanobiotechnology tool for cell biology. Nano Convergence. 3(1). doi: 10.1186/s40580-016-0082-x. Full text in Research Archive
• Alfonso, Stephanie I.; Callender, Julia A.; Hooli, Basavaraj; Antal, Corina E.; Mullin, Kristina & Sherman, Mathew A. [Show all 11 contributors for this article] (2016). Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer's disease. Science Signaling. ISSN 1945-0877. 9(427). doi: 10.1126/scisignal.aaf6209. Full text in Research Archive
• Gerner, Lisa; Munack, Steffi; Temmerman, Koen; Lawrence-Dörner, Ann-Marie; Besir, Huseyin & Wilmanns, Matthias [Show all 10 contributors for this article] (2016). Data for the co-expression and purification of human recombinant CaMKK2 in complex with calmodulin in Escherichia coli. Data in Brief. 8, p. 733–740. doi: 10.1016/j.dib.2016.06.033. Full text in Research Archive
• Falk, Samantha J.; Lee, Jaehyoun; Sekulic, Nikolina; Sennett, Michael A.; Lee, Tae-Hee & Black, Ben E. (2016). CENP-C directs a structural transition of CENP-A nucleosomes mainly through sliding of DNA gyres. Nature Structural & Molecular Biology. ISSN 1545-9993. 23(3), p. 204–208. doi: 10.1038/nsmb.3175. Full text in Research Archive
• Gunasekaran, Stalin Chellappa; Hugenschmidt, Harald; Hagness, Morten; Line, Pål Dag; Labori, Knut Jørgen & Wiedswang, Gro [Show all 8 contributors for this article] (2016). Regulatory T cells that co-express RORγt and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer. Oncoimmunology. ISSN 2162-4011. 5(4). doi: 10.1080/2162402X.2015.1102828. Full text in Research Archive
• Wehbi, Vanessa Leila & Tasken, Kjetil (2016). Molecular mechanisms for cAMP-mediated immunoregulation in T cells - role of anchored protein kinase a signaling units. Frontiers in Immunology. 7:222. doi: 10.3389/fimmu.2016.00222. Full text in Research Archive
• Schultz, Johannes Kurt; Yaqub, Sheraz & Øresland, Tom (2016). Management of diverticular disease in scandinavia. Journal of Clinical Gastroenterology. ISSN 0192-0790. 50, p. S50–S52. doi: 10.1097/MCG.0000000000000642. Full text in Research Archive
• Gunasekaran, Stalin Chellappa; Lieske, Nora Valeska; Hagness, Morten; Line, Pål Dag; Tasken, Kjetil & Aandahl, Einar Martin (2016). Human regulatory T cells control TCR signaling and susceptibility to suppression in CD4+ T cells. Journal of Leukocyte Biology. ISSN 0741-5400. 100(1), p. 5–16. doi: 10.1189/jlb.2HI0815-334R. Full text in Research Archive
• Sulen, Andre; Gullaksen, Stein-Erik; Bader, Lucius; McClymont, David; Skavland, Jørn & Gavasso, Sonia [Show all 7 contributors for this article] (2016). Signaling effects of sodium hydrosulfide in healthy donor peripheral blood mononuclear cells. Pharmacological Research. ISSN 1043-6618. 113, p. 216–227. doi: 10.1016/j.phrs.2016.08.018. Full text in Research Archive Show summary

  Hydrogen sulfide (H2S) is an endogenous gasotransmitter in human physiology and inflammatory disease, however, with limited knowledge of how signal transduction pathways are involved in immune cells. To examine the effects of sulfide on relevant intracellular signaling in human peripheral blood mononuclear cells (PBMCs), we stimulated healthy donor PBMCs with sodium hydrosulfide (NaHS, 1–1000 μM) to mimic H2S stimulation, and analyzed phosphorylation of p38 mitogen activated protein kinase (MAPK) (pT180/pY182), NF-κB p65 (pS529), Akt (pS473) and CREB/ATF1 (pS133/pS63) with flow and mass cytometry. In contrast to transient effects in subsets of lymphocytes, classical monocytes demonstrated sustained phosphorylation of p38, Akt and CREB/ATF1. NaHS induced calcium dependent phosphorylation of p38, Akt and CREB, but not NF-κB, and the phosphorylation of Akt was partly dependent on p38, indicative of p38-Akt crosstalk. Attenuation of these effects by molecules targeting p38 and Hsp90 indicated Hsp90 as a possible target for H2S-induced activation of p38. These results provide a description of a NaHS-induced signal transduction pathway in human primary immune cells that may have relevance for the role of sulfides in inflammation.

• Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Rugor, Julianna; Solano, Maria Emilia & Arck, Petra Clara [Show all 23 contributors for this article] (2016). CD74-downregulation of placental macrophage-trophoblastic interactions in preeclampsia. Circulation Research. ISSN 0009-7330. 119(1), p. 55–68. doi: 10.1161/CIRCRESAHA.116.308304. Full text in Research Archive
• Tonby, Kristian; Wergeland, Ida; Lieske, Nora Valeska; Kvale, Dag; Tasken, Kjetil & Dyrhol-Riise, Anne Ma (2016). The COX- inhibitor indomethacin reduces Th1 effector and T regulatory cells in vitro in Mycobacterium tuberculosis infection. BMC Infectious Diseases. 16:599, p. 1–12. doi: 10.1186/s12879-016-1938-8. Full text in Research Archive Show summary

  Background: Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of Mycobacterium tuberculosis (Mtb). Methods: Blood samples were obtained from patients with latent TB (n = 9) and active TB (n = 33) before initiation of anti-TB chemotherapy. COX-2 expression in monocytes and ESAT-6 and Ag85 specific T cell cytokine responses (TNF-α, IFN-γ, IL-2), proliferation (carboxyfluorescein succinimidyl ester staining) and regulation (FOXP3+ T regulatory cells) were analysed by flow cytometry and the in vitro effects of the COX-1/2 inhibitor indomethacin were measured. Results: We demonstrate that indomethacin significantly down-regulates the fraction of Mtb specific FOXP3+ T regulatory cells (ESAT-6; p = 0.004 and Ag85; p < 0.001) with a concomitant reduction of Mtb specific cytokine responses and T cell proliferation in active TB. Although active TB tend to have higher levels, there are no significant differences in COX-2 expression between unstimulated monocytes from patients with active TB compared to latent infection. Monocytes in both TB groups respond with a significant upregulation of COX-2 after in vitro stimulation. Conclusions: Taken together, our in vitro data indicate a modulation of the Th1 effector and T regulatory cells in Mtb infection in response to the COX-1/2 inhibitor indomethacin. The potential role as adjunctive host-directed therapy in TB disease should be further evaluated in both animal studies and in human clinical trials.

• Kim, Yun K; Yadava, Ramesh S; Mandal, Mahua; Mahadevan, Karunasai; Yu, Qing & Leitges, Michael [Show all 7 contributors for this article] (2016). Disease phenotypes in a mouse model of RNA toxicity are independent of protein kinase Cα and Protein Kinase Cβ. PLOS ONE. 11(9). doi: 10.1371/journal.pone.0163325. Full text in Research Archive
• Taylor, Michael; Gözen, Irep; Patel, Samir; Jesorka, Aldo & Bertoldi, Katia (2016). Peridynamic Modeling of Ruptures in Biomembranes. PLOS ONE. doi: 10.1371/journal.pone.0165947. Full text in Research Archive
• Bjerregaard-Andersen, Kaare; Østensen, Ellen; Scott, John D.; Tasken, Kjetil & Morth, Jens Preben (2016). Malonate in the nucleotide-binding site traps human AKAP18γ/δ in a novel conformational state. Acta Crystallographica. Section F : Structural Biology and Crystallization Communications. 72, p. 591–597. doi: 10.1107/S2053230X16010189. Full text in Research Archive Show summary

  A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18γ/δ are found in complex with sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca2+ release and re-uptake. For this reason, AKAP18γ/δ presents an interesting drug target with therapeutic potential in cardiovascular disease. The crystal structure of the central domain of human AKAP18γ has been determined at the atomic resolution of 1.25 Å. This first structure of human AKAP18γ is trapped in a novel conformation by a malonate molecule bridging the important R-loop with the 2H phosphoesterase motif. Although the physiological substrate of AKAP18γ is currently unknown, a potential proton wire deep in the central binding crevice has been indentified, leading to bulk solvent below the R-loop. Malonate complexed with AKAP18γ at atomic resolution provides an excellent starting point for structure-guided drug design.

• Zhang, Tianzhou; Braun, Ursula Barbara & Leitges, Michael (2016). PKD3 deficiency causes alterations in microtubule dynamics during the cell cycle. Cell Cycle. ISSN 1538-4101. 15(14), p. 1844–1854. doi: 10.1080/15384101.2016.1188237. Full text in Research Archive
• Stiksrud, Birgitte; Lorvik, Kristina Berg; Kvale, Dag; Mollnes, Tom Eirik; Ueland, Per Magne & Trøseid, Marius [Show all 8 contributors for this article] (2016). Plasma IP-10 is increased in immunological nonresponders and associated with activated regulatory T cells and persisting low CD4 counts. Journal of Acquired Immune Deficiency Syndromes. ISSN 1525-4135. 73(2), p. 138–148. doi: 10.1097/QAI.0000000000001080. Full text in Research Archive
• Liou, Geou-Yarh; Döppler, Heike; DelGiorno, Kathleen E; Zhang, Lizhi; Leitges, Michael & Crawford, Howard C. [Show all 8 contributors for this article] (2016). Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions. Cell reports. 14(10), p. 2325–2336. doi: 10.1016/j.celrep.2016.02.029. Full text in Research Archive
• Liu, Lisa L.; Landskron, Johannes; Ask, Eivind Heggernes; Enqvist, Monika; Sohlberg, Ebba & Traherne, James A. [Show all 18 contributors for this article] (2016). Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans. Cell reports. 15(3), p. 1088–1099. doi: 10.1016/j.celrep.2016.04.005. Full text in Research Archive
• Nakanishi, Yuki; Reina-Campos, Miguel; Nakanishi, Naoko; Llado, Victoria; Elmen, Lisa & Peterson, Scott [Show all 14 contributors for this article] (2016). Control of Paneth cell fate, intestinal inflammation and tumorigenesis by PKCλ/ι. Cell reports. 16. doi: 10.1016/j.celrep.2016.08.054. Full text in Research Archive
• Shabrova, Elena; Hoyos, Beatrice; Vinogradov, Valerie; Kim, Youn-Kyung; Wassef, Lesley & Leitges, Michael [Show all 8 contributors for this article] (2016). Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity. The FASEB Journal. ISSN 0892-6638. p. 1339–1355. doi: 10.1096/fj.15-281543. Full text in Research Archive
• Haller, Martina; Khalid, Sana; Kremser, Leopold; Fresser, Friedrich; Furlan, Tobias & Hermann, Martin [Show all 13 contributors for this article] (2016). Novel Insights into the PKCβ-dependent Regulation of the Oxidoreductase p66Shc. Journal of Biological Chemistry. ISSN 0021-9258. 291(45), p. 23557–23568. doi: 10.1074/jbc.m116.752766. Full text in Research Archive
• Sajan, Mini; Hansen, Barbara; Ivey, RA 3rd; Sajan, Joshua; Ari, Csilla & Song, Shijie [Show all 10 contributors for this article] (2016). Brain insulin signaling is increased in insulin-resistant states and decreases in FOXOs and PGC-1a and increases in Aβ&lt;sub&gt;1-40/42&lt;/sub&gt; and phospho-tau may abet Alzheimer development. Diabetes. ISSN 0012-1797. 65(7), p. 1892–1903. doi: 10.2337/db15-1428. Full text in Research Archive
• Arntzen, Magnus Øverlie; Boddie, Paul; Frick, Rahel; Koehler, Christian & Thiede, Bernd (2015). Consolidation of proteomics data in the Cancer proteomics database. Proteomics. ISSN 1615-9853. 15(22), p. 3765–3771. doi: 10.1002/pmic.201500144. Full text in Research Archive
• Bousquet, Paula; Sandvik, Joe Alexander; Arntzen, Magnus Øverlie; Edin, Nina Frederike J; Christoffersen, Stine & Krengel, Ute [Show all 8 contributors for this article] (2015). Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells. International Journal of Proteomics. ISSN 2090-2174. doi: 10.1155/2015/678527. Full text in Research Archive
• Luo, ZhengYuan; Güven, Sinan; Gözen, Irep; Chen, Pu; Tasoglu, Savas & Anchan, Raymond M [Show all 8 contributors for this article] (2015). Deformation of a single mouse oocyte in a constricted microfluidic channel. Microfluidics and Nanofluidics. ISSN 1613-4982. 19, p. 883–890. doi: 10.1007/s10404-015-1614-0. Full text in Research Archive
• Gözen, Irep & Jesorka, Aldo (2015). Lipid nanotube networks: Biomimetic Cell-to-Cell Communication and Soft-Matter Technology. Nanofabrication. 2, p. 27–31. doi: 10.1515/nanofab-2015-0003. Full text in Research Archive
• Landin, Maria Augusta Dos S Silva; Nygård, Ståle; Shabestari, Maziar; Babaie, Eshrat; Reseland, Janne Elin & Osmundsen, Harald (2015). Mapping the global mRNA transcritome during development of the murine first molar. Frontiers in Genetics. 6(47). doi: 10.3389/fgene.2015.00047. Full text in Research Archive Show summary

  The main objective of this study was to map global geneexpression in order to provide information about the populations of mRNA species participating in murine tooth development at 24 h intervals, starting at the eleventh embryonic day (E11.5) up to the seventh post-natal day (P7). The levels of RNA species expressed during murine tooth development were mesured using a total of 58 deoxyoligonucleotide microarrays. Microarray data was validated using real-time RT-PCR. Differentially expressed genes (p<0.05) were subjected to bioinformatic analysis to identify cellular activities significantly associated with these genes. Using ANOVA the microarray data yielded 4362 genes as being differentially expressed from the elleventh embryonic day (E11.5) up to seven days post-natal (P7), 1921 of these being genes without known functions. The remaining 2441 genes were subjected to further statistical analysis using a supervised procedure. Bioinformatic analysis results for each time-point studied suggests that the main molecular functions associated with genes expressed at the early pre-natal stages (E12.5-E18.5) studied were cell cycle progression, cell morphology, lipid metabolism, cellular growth, proliferation, senescence and apoptosis, whereas most genes expressed at post-natal and secretory stages (P0- P7) were significantly associated with regulation of cell migration, biosynthesis, differentiation, oxidative stress, polarization and cell death. Differentially expressed genes (DE) not described earlier during tooth murine tooth development; Inositol 1, 4, 5-triphosphate receptor 3 (Itpr3), metallothionein 1(Mt1), cyclin-dependent kinase 4 (Cdk4), cathepsin D (Ctsd), keratin complex 2, basic, gene 6a (Krt2-6a), cofilin 1, non-muscle (Cfl1), cyclin 2 (Ccnd2), were verified by real-time quantitative RT-PCR and showed good agreement with results obtained from microarray.

• Gözen, Irep & Dommersnes, Paul Gunnar (2014). Pore dynamics in lipid membranes. The European Physical Journal Special Topics (EPJ - Special Topics (EPJ ST)). ISSN 1951-6355. 223, p. 1813–1829. doi: 10.1140/epjst/e2014-02228-5. Full text in Research Archive
• Assal, Rami El; Güven, Sinan; Gürkan, Umut Atakan; Gözen, Irep; Shafiee, Hadi & Dalbeyler, Sedef [Show all 18 contributors for this article] (2014). Bio-Inspired Cryo-Ink Preserves Red Blood Cell Phenotype and Function During Nanoliter Vitrification. Advanced Materials. ISSN 0935-9648. 26, p. 5815–5822. doi: 10.1002/adma.201400941. Full text in Research Archive
• Fang, Evandro Fei; Scheibye-Knudsen, Morten; Brace, Lear E; Kassahun, Henok; Sengupta, Tanima & Nilsen, Hilde [Show all 9 contributors for this article] (2014). Defective Mitophagy in XPA via PARP-1 Hyperactivation and NAD+/SIRT1 Reduction. Cell. ISSN 0092-8674. 157(4). doi: 10.1016/j.cell.2014.03.026. Full text in Research Archive Show summary

  Mitochondrial dysfunction is a common feature in neurodegeneration and aging.We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA-deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD+-SIRT1-PGC-1a axis triggered by hyperactivation of the DNA damage sensor PARP- 1. This phenotype is rescued by PARP-1 inhibition or by supplementation with NAD+ precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a nuclearmitochondrial crosstalk that is critical for the maintenance of mitochondrial health.

• Jourdain, Isabelle; Brzezińska, Elspeth A. & Toda, Takashi (2013). Fission Yeast Nod1 Is a Component of Cortical Nodes Involved in Cell Size Control and Division Site Placement. PLOS ONE. 8(1). doi: 10.1371/journal.pone.0054142. Full text in Research Archive
• Gözen, Irep; Shaali, Mehrnaz; Ainla, Alar; Örtmen, Bahanur; Põldsalu, Inga & Kustanovich, Kiryl [Show all 10 contributors for this article] (2013). Thermal migration of molecular lipid films as a contactless fabrication strategy for lipid nanotube networks. Lab on a Chip. ISSN 1473-0197. 13, p. 3822–3826. doi: 10.1039/C3LC50391G. Full text in Research Archive
• Ainla, Alar; Gözen, Irep; Hakonen, Bodil & Jesorka, Aldo (2013). Lab on a Biomembrane: Rapid prototyping and manipulation of 2D fluidic lipid bilayer circuits. Scientific Reports. 3. doi: 10.1038/srep02743. Full text in Research Archive
• Gözen, Irep; Örtmen, Bahanur; Põldsalu, Inga; Dommersnes, Paul Gunnar; Orwar, Owe & Jesorka, Aldo (2013). Repair of large area pores in supported double bilayers. Soft Matter. ISSN 1744-683X. 9, p. 2787–2792. doi: 10.1039/C3SM27429B. Full text in Research Archive
• Gözen, Irep; Dommersnes, Paul Gunnar; Orwar, Owe & Jesorka, Aldo (2012). Evidence for membrane flow through pores in stacked phospholipid membranes. Soft Matter. ISSN 1744-683X. 8, p. 6220–6225. doi: 10.1039/C2SM25629K. Full text in Research Archive
• Gözen, Irep & Jesorka, Aldo (2012). Instrumental Methods to Characterize Molecular Phospholipid Films on Solid Supports. Analytical Chemistry. ISSN 0003-2700. 84 (2), p. 822–838. doi: 10.1021/ac203126f. Full text in Research Archive
• Gözen, Irep; Billerit, Celine; Dommersnes, Paul Gunnar; Jesorka, Aldo & Orwar, Owe (2011). Calcium-ion-controlled nanoparticle-induced tubulation in supported flat phospholipid vesicles. Soft Matter. ISSN 1744-683X. 7, p. 9706–9713. doi: 10.1039/C1SM05677H. Full text in Research Archive
• Gözen, Irep; Dommersnes, Paul Gunnar; Czolkos, Ilja; Jesorka, Aldo; Lobovkina, Tatsiana & Orwar, Owe (2010). Fractal avalanche ruptures in biological membranes. Nature Materials. ISSN 1476-1122. 9, p. 908–912. doi: 10.1038/nmat2854. Full text in Research Archive
• Gözen, Irep & Örmeci, Banu (2010). Effect of daylight on regrowth of bacteria in anaerobically digested sludge. Water Science and Technology. ISSN 0273-1223. 62 (2) , p. 364–369. doi: 10.2166/wst.2010.268. Full text in Research Archive
• Lobovkina, Tatsiana; Gözen, Irep; Erkan, Yavuz; Olofsson, Jessica; Weber, Stephen G. & Orwar, Owe (2010). Protrusive growth and periodic contractile motion in surface-adhered vesicles induced by Ca2+-gradients. Soft Matter. ISSN 1744-683X. 6, p. 268–272. doi: 10.1039/B916805M. Full text in Research Archive
• Ainla, Alar; Gözen, Irep; Orwar, Owe & Jesorka, Aldo (2009). A Microfluidic Diluter Based on Pulse Width Flow Modulation. Analytical Chemistry. ISSN 0003-2700. 81 (13), p. 5549–5556. doi: 10.1021/ac9010028. Full text in Research Archive

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• Gözen, Irep; Dommersnes, Paul Gunnar & Jesorka, Aldo (2015). Lipid Self-Spreading on Solid Substrates. IntechOpen. ISBN 9789535122166. 36 p. Full text in Research Archive
• Gözen, Irep (2013). The self–spreading double bilayer/Advances in Lipid Membrane Nanotechnology. Chalmers University of Technology. ISBN 9789173858137. 110 p. Full text in Research Archive

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• Nissen-Meyer, Lise Sofie Haug & Chaudhry, Farrukh Abbas (2017). Corrigendum: Protein kinase C phosphorylates the system N glutamine transporter SN1 (Slc38a3) and regulates its Membrane trafficking and Degradation [Front Endocrinol, 4, (2013) (138)] doi: 10.3389/fendo.2013.00138. Frontiers in Endocrinology. 8:190, p. 1–2. doi: 10.3389/fendo.2017.00190. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara Louise; Donaldson, Ian M; Haraldsen, Guttorm & Bogen, Bjarne [Show all 7 contributors for this article] (2016). Kreft-spesifikke betennelsesreaksjoner kan beskytte mot kreft. Bestpractice Onkologi/Hematologi. ISSN 2245-0440. February. Full text in Research Archive
• Ribes, Anna Maria Parente; Skånland, Sigrid Strand; Bürgler, Simone; Os, Audun; Wang, Dong & Bogen, Bjarne [Show all 9 contributors for this article] (2016). Spleen tyrosine kinase inhibitors reduce CD40l-induced proliferation of chronic lymphocytic leukemia cells but not normal B cells. Haematologica. ISSN 0390-6078. 101(2), p. e59–e62. doi: 10.3324/haematol.2015.135590. Full text in Research Archive
• Johnsen, Guro Mørk; Sheng, Vincent O.Y.; Tasken, Kjetil; Staff, Anne Cathrine & Malmberg, Karl-Johan (2015). Killer immunoglobulin-like receptors (KIRS) on 3rd trimester decidual natural killer cells. Journal of Reproductive Immunology. ISSN 0165-0378. 111, p. 11–11. doi: 10.1016/j.jri.2015.06.073. Full text in Research Archive
• Razick, Sabry & Donaldson, Ian Matthew (2010). iRefIndex : Interaction Reference Index : International Conference on Intelligent Systems for Molecular Biology (ISMB), Stockholm, Sweden, June 27-July 02, 2009 : Poster E29. Universitetet i Oslo. Full text in Research Archive Show summary

  iRefIndex provides an index of protein interactions available in a number of primary interaction databases. This index allows the user to search for a protein and retrieve a non-redundant list of interactors for that protein. This system uses the Redundant Object Group (ROG) and Redundant Interaction Group (RIG) identifier to group proteins and interactions into redundant groups. This method allows users to integrate their own data with the iRefIndex in a way that ensures proteins with the exact same sequence and NCBI taxonomy identifier will be represented only once. iRefIndex has consolidated 10 different interaction databases using this method and provides a number of methods to access these data. This includes downloading as PSI-MI compliant tab-delimited file and from the iRefScape plugin for (http://www.cytoscape.org/), PSICQUIC web services and the iRefWeb(http://wodaklab.org/iRefWeb/). More details about iRefIndex and links available at: http://irefindex.uio.no/wiki/iRefIndex

• Razick, Sabry & Donaldson, Ian Matthew (2010). Design and prototype of a system to integrate and visualize biological interaction data : International Conference on Intelligent Systems for Molecular Biology (ISMB), Vienna, Austria: (July 21-25, 2007) : Poster. Universitetet i Oslo. Full text in Research Archive Show summary

  Biomolecular interaction data is an increasingly important bioinformatics dataset used to examine biological systems. However, these data are spread across multiple databases and expressed in disparate data structures and formats. A prerequisite for working with these data would be consolidation into a single non-redundant updated repository. An initial design and prototype for consolidating and visualizing interaction data will be presented in this poster with an especial emphasis on providing scalable and reliable web-services as part of the solution. The central point of operation is a data warehouse with numerous parsers retrieving updated information from existing data sources. We have designed parsers for PSI-MI 1.0, PSI-MI 2.5 XML files and tab delimited text files. The parsers for XML files are built using an event-driven pull-parsing API which gives them the ability to handle very large files. A local application interface provides access to this data warehouse for local programmers, java servlets and web services. The usage of various operating systems and programming languages by the intended clients were considered when designing the system. Therefore, platform independent protocols were used. Moreover, multiple implementations of hosting the services were considered with respect to their ability to handle large data sets reliably in a stateful manner. Using these web-services, a tool was developed to retrieve and present interaction data visually. The approach taken was to construct modules as plugins to existing molecular visualization software.

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