Siste publikasjoner

• Sengupta, Poushali; Khadka, Rabindra; Maharjan, Sabita; Eliassen, Frank; Pandey, Shashi Raj & Zhang, Yan [Vis alle 8 forfattere av denne artikkelen] (2026). Explainability of Complex AI Models with Correlation Impact Ratio. IEEE Transactions on Artificial Intelligence (TAI). s. 14–14. doi: 10.1109/tai.2026.3732283. Fulltekst i vitenarkiv
• Dyhr, Emma; Pinedo, Lucía Cañete de; Frederiksen, Nicki; Bojer, Martin Saxtorph; Ingmer, Hanne & Sæbø, Ingvill Pedersen [Vis alle 11 forfattere av denne artikkelen] (2026). Antibacterial peptidomimetics via fragment display on small-molecule scaffolds. RSC Medicinal Chemistry. ISSN 2632-8682. 17(4), s. 1989–2001. doi: 10.1039/d5md00916b. Fulltekst i vitenarkiv
• Hubers, Lisa Anne; Skjetne, Alexander Myhr; Luna, Luisa; Lefol, Yohan Pierre; Lund, Solveig Osnes & Wågbø, Ane Marit [Vis alle 15 forfattere av denne artikkelen] (2026). Functional impact of Nth like DNA glycosylase 1 on mitochondrial dynamics. Nucleic Acids Research (NAR). ISSN 0305-1048. 54(17). doi: 10.1093/nar/gkag876. Fulltekst i vitenarkiv Vis sammendrag

  Nth like DNA glycosylase 1 (NTHL1), a key base excision repair enzyme, has long been considered essential for nuclear and mitochondrial genome integrity. Combining in vitro biochemical assays, in cellulo molecular biology, and bioinformatic analyses, we investigated how NTHL1 loss affects mitochondrial DNA (mtDNA) stability and mitochondrial function. Contrary to the conventional view that mtDNA damage is solely detrimental, we find that NTHL1 loss confers a beneficial, mitochondria-initiated phenotype in human cells. Despite accumulating mtDNA lesions, NTHL1 loss unexpectedly increases mtDNA copy number, elevates oxidative phosphorylation protein levels, and enhances mitochondrial respiration. NTHL1−/− cells also show increased mitochondrial mass and higher levels of the biogenesis regulator PGC1α and the fusion protein OPA1, indicating an adaptive response that boosts mitochondrial function and capacity. Consequently, NTHL1−/− cells exhibit resistance to mitochondrial stress, accompanied by increased eIF2α phosphorylation and reduced MYC levels, converging on a broader transcriptional adaptive program. This phenotype depends on mitochondrial NTHL1 and reactive oxygen species (ROS) signaling, since treatment with ROS scavengers or mitochondria-specific reintroduction of NTHL1 rescues it. Together, these findings position NTHL1 as a key modulator of mtDNA stability and mitochondrial function, revealing that loss of this DNA repair enzyme shifts cellular metabolism toward a stress-adaptive state and enhances resilience to oxidative stress.

• Dyhr, Emma; Sæbø, Ingvill Pedersen; Riisnæs, Ida Mathilde Marstein; Bjørås, Magnar; Helgesen, Emily & Booth, James Alexander [Vis alle 7 forfattere av denne artikkelen] (2026). Antimicrobial Peptides Based on the TisB Toxin: Toward Enhanced Activity and Synergy with Antibiotics. ACS Omega. 11(26), s. 38837–38847. doi: 10.1021/acsomega.6c02137. Fulltekst i vitenarkiv
• Myhre, Vegard; Kaarbø, Mari; Yang, Mingyi; Fevang, Børre; Sousa, Mirta Mittelstedt Leal de & Reims, Henrik Mikael [Vis alle 11 forfattere av denne artikkelen] (2026). Altered duodenal N6-methyladenosine levels in common variable immunodeficiency associate with duodenal microbiota. Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1875823. Fulltekst i vitenarkiv
• Søraas, Arne Vasli Lund; Engvig, Andreas; Alnæs, Dag; Karim, Lana Nagmadin; Danilova, Elena & Istre, Mette Stausland [Vis alle 17 forfattere av denne artikkelen] (2026). Interstitial fluid rejuvenation through young-donor plasma exchange in cognitively impaired patients: a pilot safety and feasibility study. GeroScience. ISSN 2509-2715. doi: 10.1007/s11357-026-02435-0. Fulltekst i vitenarkiv Vis sammendrag

  Heterochronic parabiosis improves physiological and cognitive function in aging rodents; these benefits appear to be derived from the removal of aged blood plasma components and the addition of younger ones. In humans, removing plasma from older individuals with Alzheimer’s disease (AD) and replacing it with saline and albumin delayed cognitive deterioration in a large clinical trial. However, mimicking heterochronic parabiosis in humans by removing large volumes of a patient’s blood plasma and replacing it with plasma from young and healthy donors has not been tested. Here, we have performed a pilot study to characterize the feasibility and safety of such a procedure, replacing between 16 and 26 L of patient blood plasma with young (ages 18–24) donor blood plasma for twelve patients who recently received a diagnosis of mild cognitive impairment with biomarker evidence of AD. The dose and time interval between plasma exchanges was tailored to maximize equilibration of donor plasma components into the interstitial fluid, with the aim of achieving what we term interstitial rejuvenation. We explored three permutations of a plasma exchange protocol with different treatment intensities and doses, each performed on three to five patients. We present data on safety, feasibility, patient burden, resource use of the treatments, preliminary measurements of clinical variables, and short-term cognitive trajectories in the patients. The procedures were feasible, and the adverse events observed were consistent with known risks of plasma exchange, supporting further investigation of treatment efficacy in a larger controlled trial. This safety and feasibility study was first registered 22 December 2023 at ClinicalTrials.gov and given the identifier NCT06234436.

• Mikkelsen, Thea Falkenberg; Vera-Rodriguez, Maria; Fedorcsák, Zsofia; Greggains, Gareth; Fedorcsak, Peter Zoltan & Hald, Kirsten (2026). Reduced endometrial LIF expression in women with uterine fibroids and its restoration following myomectomy. European Journal of Obstetrics, Gynecology, and Reproductive Biology. ISSN 0301-2115. 326, s. 115340–115340. doi: 10.1016/j.ejogrb.2026.115340. Fulltekst i vitenarkiv
• Suaste, Veronica; Presterud, Rebecca; Wennerström, Anna Berit; Wang, Heling; Zhang, Jianying & Lund, Solveig Osnes [Vis alle 16 forfattere av denne artikkelen] (2026). Transcriptional Profiling Shows Dampening of Interferon Gene Signatures by NAD Augmentation in Ataxia-Telangiectasia. International Journal of Molecular Sciences. ISSN 1661-6596. 27(13). doi: 10.3390/ijms27135652. Fulltekst i vitenarkiv Vis sammendrag

  Ataxia-Telangiectasia (A-T) is a multisystem disorder caused by loss of A-T mutated (ATM) protein activity, characterized clinically by immunodeficiency and cerebellar ataxia. ATM is a master regulator of DNA damage responses and loss of ATM function is accompanied by persistent activation of PARP1 leading to depletion of intracellular NAD+ and dysfunction of a series of cellular signalling pathways dependent on NAD+, providing a mechanistic rationale for NAD+ augmentation therapy. We performed a clinical trial of NAD+ augmentation with nicotinamide riboside (NR) over 24 months in A-T patients where we observed improved coordination and eye movements in A-T patients. Here, by using peripheral blood mononuclear cells, we performed longitudinal transcriptome profiling to define molecular signatures of A-T and to assess pathway-level responses to NR supplementation. A-T patients exhibited reproducible transcriptomic alterations involving immune, vascular, and inflammatory pathways. NAD+ augmentation was associated with suppression of interferon response genes and modulation of networks correlated with neurological improvement. These findings establish systemic molecular signatures of A-T and identify potential blood-based biomarkers that reflect disease processes and therapeutic response, supporting the use of NAD+ augmentation as a disease-modifying strategy in A-T by dampening interferon signalling.

• Belhaj, Imen; Åmellem, Ingrid; Tartanoglu, Can H.; Weidemann, Hanne Margrete; Vallenari, Evan Michael & Yang, Mingyi [Vis alle 10 forfattere av denne artikkelen] (2026). Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer’s and wild-type mice. Scientific Reports. 16(1). doi: 10.1038/s41598-026-48154-6. Fulltekst i vitenarkiv Vis sammendrag

  Lactate, a well-known metabolite and signalling molecule, holds therapeutic potential for neurodegenerative diseases. Here, we investigated the effects of chronic lactate treatment on cognition and molecular biomarkers in the 5XFAD mouse model of Alzheimer’s disease (AD) and in wild-type (WT) controls using behavioural testing alongside proteomic and transcriptomic analyses. Mice received lactate or vehicle injections 4 days per week for 11 weeks, with behavioural testing before and after the treatment period. Lactate improved working memory in late-treated AD mice, without eliciting anxiety-like behaviour. At the molecular level, lactate reduced Il1b expression, and in a sex-dependent manner, normalised NEFL, and enhanced synaptic integrity proteins (OPCML, PPFIA2, STXBP3, SYT1, VGLUT2, VSNL1) in AD mice, while also augmenting mitochondrial regulators (ATP5G2, GRPEL1, SLC25A23) across genotypes. Notably, lactate upregulated low-abundance ionotropic glutamate receptor mRNAs (Grik3, Grin2c, Grid2ip) in female AD mice, indicating enhanced glutamatergic signalling. In WT mice, lactate increased expression of neurotrophic factors (Bdnf, Igf1, Vegfa), anti-inflammatory cytokines (Il4 and Il13), and the neuronal lactate transporter Mct2, suggesting promoted neuronal resilience. Together, these findings indicate that lactate treatment can mitigate cognitive decline and enhance molecular pathways of resilience in AD, warranting larger, age-stratified studies to validate its therapeutic potential and elucidate underlying mechanisms.

• Crisan, Andrea Pop; Ciocan, Cristina; Pirlog, Radu; Necula, Alexandru; Hajjar, Darius Adin Al & Pruteanu, Lavinia Lorena [Vis alle 11 forfattere av denne artikkelen] (2026). Molecular Signatures and Network Alterations Underlying GBM Progression and Recurrence. Medicina. ISSN 1010-660X. 62(2). doi: 10.3390/medicina62020336. Fulltekst i vitenarkiv
• Yadav, Ajay; Richartz, Nina; Bhagwat, Sampada; Burman, Marta Maria; Munthe-Kaas, Monica Cheng & Skålhegg, Bjørn Steen [Vis alle 9 forfattere av denne artikkelen] (2026). Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice. Journal of Biological Chemistry. ISSN 0021-9258. 302(3). doi: 10.1016/j.jbc.2026.111143. Fulltekst i vitenarkiv Vis sammendrag

  Most children with acute lymphoblastic leukemia (ALL) achieve long-term survival due to intensive multimodal chemotherapy. However, the use of cytotoxic DNA-damaging agents is frequently associated with severe long-term side effects, prompting continued efforts to improve treatment strategies. This study explores the potential of starving the leukemic cells to enhance the efficacy of DNA-damaging therapy in ALL. Previous work demonstrated that cAMP signaling attenuates DNA damage-induced apoptosis in ALL cells, both in vitro and in a xenograft model. The current findings show that glucose and serum deprivation reverse the effect of cAMP, converting it from a survival factor to a promoter of DNA damage-induced apoptosis in ALL-derived cell lines and patient-derived leukemic cells in vitro. The starvation-induced sensitization was independent of p53 but was shown to require increased levels of reactive oxygen species (ROS). In turn, the elevated ROS levels enhanced the activation of the mitogen-activated protein kinase p38 (p38 MAPK). The resulting augmented cell death was inhibited both by the ROS scavenger N-acetyl cysteine and the p38 MAPK inhibitor SB 202190. The translational potential of increasing the efficacy of DNA damaging agents in starving ALL cells was supported by in vivo data showing that intermittent fasting, combined with subtherapeutic doses of irradiation, significantly inhibits the leukemia progression in a xenograft model of severe combined immunodeficiency mice.

• Lier, Silje; Markusson, Sara Bachmann; Kocijančič, Anja; Narum, Martine; Lund, Solveig Osnes & Böllering, Bianka [Vis alle 30 forfattere av denne artikkelen] (2026). CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma. EMBO Molecular Medicine. ISSN 1757-4676. 18, s. 1592–1624. doi: 10.1038/s44321-026-00393-w. Fulltekst i vitenarkiv Vis sammendrag

  Glioblastomas are the most prevalent and aggressive malignant brain tumors, characterized by hypertranscription and dependence on neurodevelopmental transcription factors. The transcriptional cycle is regulated by phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) by transcriptional cyclin-dependent kinases (tCDKs), including CDK7, CDK9, CDK12, and CDK13. Here we find that glioblastoma stem cells (GSCs) are selectively sensitive to CDK12/CDK13 inhibition, whereas CDK7 and CDK9 inhibition cause non-specific cytotoxicity. This selective targeting halts GSC and organoid proliferation, curtails GSC invasion and suppresses tumor growth in a xenograft mouse model. In GSCs, CDK12/CDK13 inhibition leads to a rapid and genome-wide loss of serine-2 phosphorylation (pSer2) of the RNAPII CTD, abolishing transcriptional elongation and a transcriptional program sustained by key neurodevelopmental transcription factors. CDK12/CDK13 inhibition unexpectedly arrests DNA replication and replication fork progression in a manner distinct from the effect of inhibiting other tCDKs. This dramatic arrest precedes DNA damage response activation and cell cycle arrest, directly linking RNAPII elongation to replication fork dynamics and revealing a previously unrecognized dependence of DNA replication on CDK12/CDK13-RNAPII regulation.

• Lagartos, Maria Jose Donate; Doncel, Beatriz Escobar; Zhang, Shi-qi; Pan, Junping; González, Noemí Villaseca & Anisimov, Aleksander [Vis alle 22 forfattere av denne artikkelen] (2026). Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD+. Brain. ISSN 0006-8950. 149(4), s. 1208–1223. doi: 10.1093/brain/awaf261. Fulltekst i vitenarkiv Vis sammendrag

  Downregulation and inactivation of the Repressor Element 1-Silencing Transcription factor (REST) is shown in Alzheimer’s disease (AD) and likely contributes to its progression, but the exact molecular mechanism linking REST reduction to AD remains unclear. We examined changes in REST expression in the entorhinal cortex and hippocampus across different Braak stages of tauopathy. We show that alterations in REST expression and sub-cellular localization are partially responsible for AD pathology, as REST overexpression improves cognition, reduces amyloid-β and phosphorylated Tau deposition, and restores mitochondrial and synaptic homeostasis. Mechanistically, the NAD+/SIRT1 axis modulates REST expression through chromatin remodelling in the promoter region of REST, leading to changes in the expression of REST target genes involved in mitophagy and synaptic function. These findings reveal a new mechanism of action for NAD+ and highlight REST as a promising therapeutic target for AD therapy.

• Alsøe, Lene; Brackmann, Stephan Andreas; Liu, Yan; Wennerström, Anna Berit; Esbensen, Qin Ying & Kalyanasundaram, Sumana [Vis alle 10 forfattere av denne artikkelen] (2026). The Role of Nuclear APOBEC Enzymes in Neoplastic Progression of Ulcerative Colitis. Clinical and Experimental Gastroenterology. 19. doi: 10.2147/CEG.S588161. Fulltekst i vitenarkiv Vis sammendrag

  Aberrant expression of the cytidine DNA deaminase AID in enterocytes within inflamed mucosa in ulcerative colitis (UC) patients has been proposed to be involved in progression of UC to colitis-associated colorectal cancer (CA-CRC). Here, we followed the expression of AID and other nuclear cytidine DNA deaminases of the APOBEC family through several stages of progression of UC in a CA-CRC case (UC progressor) and in a cohort of UC progressors and non-progressors. In inflamed and high-grade dysplastic mucosa, AICDA and APOBEC1 mRNAs, but not APOBEC3-family enzyme mRNAs, were overexpressed compared to non-inflamed tissue. Immunohistochemical staining did not show expression of AID or APOBEC3 enzymes in the enterocytes, neither in specimens from the CA-CRC case nor in biopsies from the progressor and non-progressor cohort. APOBEC1 was highly expressed in the enterocytes throughout the colorectum from the CA-CRC case and in most biopsies examined from the progressor and non-progressor cohort. The expression was not correlated with the histology of the mucosa or the progression status of the patients. In the CA-CRC case, we identified AID- and APOBEC3-associated mutation signatures in inflamed, high-grade dysplasia and cancer genomes. In conclusion, our findings suggest that AID or other nuclear APOBECs are unlikely to drive the progression of UC to CA-CRC late during course of UC. However, we cannot exclude the possibility that bursts of AID and nuclear APOBEC3 activity may contribute to formation of genome instability in early phases of disease development.

• Fossmark, Reidar; Hjorth-Hansen, Henrik; Lirussi, Lisa; Lüders, Torben; Visnovska, Martina & Liu, Yan [Vis alle 9 forfattere av denne artikkelen] (2026). Telomere Length in Celiac Disease in a Population-Based Cohort: A HUNT Study. Clinical and Translational Gastroenterology. 17(6). doi: 10.14309/ctg.0000000000001020. Fulltekst i vitenarkiv Vis sammendrag

  INTRODUCTION: Celiac disease (CeD) occurs in genetically predisposed individuals who are exposed to dietary gluten proteins. Genome-wide association studies have found CeD to be associated with a genetic predisposition to shorter telomere length. It was therefore of interest to measure leukocyte telomere length in a large cohort of patients with CeD. METHODS: This study was population-based and included a defined cohort of patients with CeD in the Trøndelag Health Study. Leukocyte telomere length was measured by quantitative polymerase chain reaction (PCR) in patients and controls 1:2 matched for age, sex, alcohol, and tobacco use. RESULTS: The study population consisted of 58.7% women, with mean age 43 (SD 14.5) years, where half were never smokers, and the majority consumed little or no alcohol. Telomer length in 1,077 patients with CeD did not differ significantly from 2,147 matched controls, 10.39 kb (SD 2.21) vs 10.52 kb (SD 2.25), P = 0.088. In a mixed linear model, we found higher age and alcohol consumption, but not tobacco use or sex, to be associated with shorter telomere length. The telomere length did not differ between patients with newly diagnosed and known CeD. DISCUSSION: This large population-based study provides evidence that CeD is not associated with clinically meaningful telomere shortening.

• Følling, Ivar; Selle, Maria Lie; Nilsen, Hogne Røed; Wennerström, Anna Berit; Nilsen, Hilde & Eide, Tor Jacob (2026). Distribution of glucagon-like peptide 1 receptor and insulin in phaeochromocytomas. Endocrine Connections. 15(1). doi: 10.1530/ec-25-0338. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Most phaeochromocytomas produce insulin, and some produce glucagon-like peptide 1 receptor (GLP-1R). In pancreatic β-cells, stimulation of GLP-1R causes insulin release. A few phaeochromocytoma patients experience hypoglycaemic attacks. Therefore, we studied the distribution of GLP-1R-containing and insulin-containing phaeochromocytoma cells and their relation. Methods In 20 phaeochromocytomas, we performed sequential double staining with anti-insulin and anti-GLP-1R antibodies and, in selected cases, staining with anti-insulin alone. We quantified tumour cells with positive staining and compared their distribution to that of randomly distributed cells using simulations. We obtained GLP-1R transcript data from 182 such tumours from The Cancer Genome Atlas (TCGA) Research Network. Results GLP-1R-containing cells were found in six of the 20 tumours, and insulin-containing cells were found in fifteen. Moreover, in the TCGA cohort, almost half of the tumours produce GLP-1R transcripts, and patients with the highest number of transcripts show longer disease-free survival. In the tumours, we found that cells expressing insulin were present in the cytoplasm and GLP-1R in the membrane, with a frequency of 2.59 and 1.34%, respectively. These cells showed clustering, and one tumour showed a large clonal expansion. Interestingly, we found deposits of insulin, which we suggest naming insulin bodies in two tumours. Very few cells contained both proteins. Conclusion Most phaeochromocytomas contain tumour cells producing insulin. About half produce GLP-1R. The producing cells show clustering, and clonal expansion occurs. Insulin release might cause hypoglycaemia. Increased GLP-1R levels might induce less aggressive tumours.

• Zhu, Hengyi; Eide, Dag Markus; Maremonti, Erica; Nilsen, Hilde & Brede, Dag Anders (2026). Mechanistic insight into the reprotoxic effects of chronic gamma radiation on spermatogenesis in Caenorhabditis elegans. Science of the Total Environment. ISSN 0048-9697. 1016. doi: 10.1016/j.scitotenv.2026.181444. Fulltekst i vitenarkiv Vis sammendrag

  Ionizing radiation is a potent genotoxic agent that may cause detrimental effects on reproductive processes. This study investigated cellular events and transcriptomic alterations underlying reproductive defects caused by chronic gamma (γ) radiation in Caenorhabditis elegans (C. elegans). Continuous exposure (100 mGy/h; total dose: 4.8 Gy) throughout larval development reduced spermatid counts (38.8%) and total brood size (26.4%). It also resulted in delayed and attenuated residual body (RB) formation (22.8%), implicating reduced number of spermatocytes or failed meiosis. Targeted exposure of early L3 to L4 (24-h, total dose 2.4 Gy) after the establishment of the primary spermatocyte population resulted in 26% reduction in brood size, thus implicating damage inflicted during meiosis as detrimental to spermatogenesis. The reprotoxic defects were markedly exacerbated by rad-51 RNAi or polq-1 deletion, confirming the crucial roles for homologous recombination (HR) and polymerase theta-mediated end joining (TMEJ) in mitigating radiation-induced reproductive damage. Phenotypical investigation of the male gonad revealed genotoxic effects including shortened mitotic zone and increased cell-cycle arrest. However, the postmeiotic stage assessed as the quantity of RB-containing phagosomes remained unaffected by ionizing radiation. Transcriptomic profiling of irradiated males showed comprehensive enhanced stress response and mitophagy accompanied by alterations of energy metabolism. Comparative transcriptomic analysis revealed large differences between sexes, where the only shared enrichment term was mitochondrial translation termination. Collectively, our results show that detrimental effects to hermaphrodite spermatogenesis occur during the meiotic phase, which leads to fewer RBs and spermatids, with a corresponding reduction in reproduction.

• Kamyshnyi, Oleksandr; Kamyshna, Iryna; Petakh, Pavlo; Halabitska, Iryna; Bjørås, Magnar & Oksenych, Valentyn [Vis alle 8 forfattere av denne artikkelen] (2025). Towards molecular diagnostics of parental alienation. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 82(1). doi: 10.1007/s00018-025-05895-3. Fulltekst i vitenarkiv Vis sammendrag

  High-conflict parental divorce can result in parental alienation (PA), leading to chronic psychological stress in children that adversely affects their mental and physical health. This stress may manifest as anxiety, depression, eating disorders, immune dysfunction, and cardiovascular, neurological, endocrine, or gastrointestinal issues. The inconsistent legal recognition of PA highlights the need for objective diagnostic tools to inform judicial decisions. We propose a panel of molecular biomarkers, derived from well-established indicators of chronic stress, to address the limited data specific to PA. This panel targets hypothalamic-pituitary-adrenal (HPA) axis activation, neurotransmitter dysregulation, inflammation, oxidative stress, epigenetic modifications, and gut microbiota dysbiosis. Interdisciplinary collaboration among researchers, general practitioners, and legal professionals is crucial to validate and implement this panel, ultimately enhancing child welfare through early intervention.

• Ravlo, Erlend; Ianevski, Aleksandr; Wolska, Waleria; Schjølberg, Jørn-Ove; Quilez, Maria Camara & Nordli, Ine Emilie Olsen [Vis alle 23 forfattere av denne artikkelen] (2025). Combination of vemurafenib, pleconaril, and AG7404 attenuates enterovirus replication in vitro and in vivo. NAR Molecular Medicine. 3(1). doi: 10.1093/narmme/ugaf046. Fulltekst i vitenarkiv Vis sammendrag

  Enteroviruses infect multiple human tissues and cause diseases including meningitis, the common cold, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, type 1 diabetes, hand, foot, and mouth disease. Despite this burden, no antiviral therapy has been approved to date. Progress has been limited by the structural and topical diversity of enteroviruses because many variants are intrinsically insensitive to candidate agents and sensitive strains develop resistance rapidly. Here, we report that the approved anticancer drug vemurafenib inhibited replication of some tested enteroviruses in cell cultures. Passage of echovirus EV1 and coxsackievirus CVB5 for six cycles in cell culture yielded vemurafenib-resistant virus variants harboring mainly missense mutations in the viral 3A and VP1 proteins, underscoring the need for combination therapy. We therefore evaluated cocktails, combining vemurafenib with the VP1 inhibitor pleconaril and the 3C protease inhibitor AG7404. In cell culture, the cocktails suppressed replication of all seven tested enteroviruses. The combination was also effective in human pancreatic, retinal, and brain organoids. In infected mice, the triple regimen reduced viral titers in the pancreas. These findings support multi-stage targeting of the enterovirus life cycle as a promising path toward broadly active therapeutic cocktails.

• Kaarbø, Mari; Yang, Mingyi; Meyer-Myklestad, Malin Holm; Sundaram, Arvind; Sousa, Mirta & Sharma, Animesh [Vis alle 13 forfattere av denne artikkelen] (2025). Transcriptomic and proteomic profiling reveal immune and metabolic dysregulation in the colonic mucosa of people living with HIV with incomplete immune recovery. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1635523. Fulltekst i vitenarkiv Vis sammendrag

  Background People living with HIV are called immunological non-responders (INR) when their CD4+ T cell count is not restored to immunocompetent levels, despite successful viral suppression. INR have increased risk of progression to AIDS, non-AIDS related morbidity, and death. Impaired mucosal barrier function is a prevailing hypothesis for why INR among people with HIV (PWH) have persistently low CD4+ T cell counts. Objective To understand the molecular mechanisms behind incomplete immune recovery in INR, we analyzed gene regulation and protein expression in gut tissues from INR, immunological responders (IR) and healthy controls (HC). Methods The transcriptome was assessed by RNA-sequencing (RNA-seq) and the proteome was examined using shotgun proteomic mass spectrometry in mucosal biopsies from the sigmoid colon and terminal ileum. Results In INR compared to IR, we identified 3326 differentially expressed genes (DEGs) in the colon while no DEGs were observed in the ileum. Gene ontology (GO) analyses revealed that the DEGs in colon of INR, compared to IR, predominantly involved pathways related to immune response, metabolism, and cellular processes. Notably, GO analysis highlighted downregulation of genes associated with B cell-mediated immunity and adaptive responses in INR. Deconvolution analysis indicated that these transcriptomic changes were not solely due to shifts in immune cell composition. Proteomic analysis supported these findings, showing more differential protein composition between INR and IR in colon than ileum. These proteins are associated with the regulation of adaptive immune signaling and essential cellular processes, including cell signaling, tissue repair, and growth, all of which are characteristic features of inflammatory bowel disease (IBD). Conclusion Our findings suggest that incomplete immune recovery during anti-retroviral therapy in PWH is associated with specific dysregulations in the molecular environment of the sigmoid colon, which may share mechanisms with IBD. The identified macromolecules may serve as potential targets for adjuvant treatment to improve the prognosis for INR.

• Starheim, Eirin Johannessen; Manaf, Adeel; Hashim, Adnan; Andersen, Niklas Nonboe; Ravlo, Erlend & Wang, Wei [Vis alle 12 forfattere av denne artikkelen] (2025). Rapid DNA and RNA isolation from few or single cells using low-cost NAxtra magnetic nanoparticles. Scientific Reports. 15(1). doi: 10.1038/s41598-025-05770-y. Fulltekst i vitenarkiv
• Berg, Sigrid Ravn; Brambilla, Alessandro; Hagen, Lars; Sharma, Animesh; Vågbø, Cathrine Broberg & Liabakk, Nina-Beate [Vis alle 11 forfattere av denne artikkelen] (2025). Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells. International Journal of Molecular Sciences. ISSN 1661-6596. 26(18). doi: 10.3390/ijms26189075. Fulltekst i vitenarkiv Vis sammendrag

  Isocitrate dehydrogenase 1 (IDH1) mutations are key drivers of glioma biology, influencing tumor aggressiveness and treatment response. To elucidate their molecular impact, we performed proteome analysis on patient-derived (PD) and U87MG glioma cell models with either mutant or wild-type IDH1. We quantified over 6000 protein groups per model, identifying 1594 differentially expressed proteins in PD-AS (IDH1MUT) vs. PD-GB (IDH1WT) and 904 in U87MUT vs. U87WT. Both IDH1MUT models exhibited enhanced MHC antigen presentation and interferon signaling, indicative of an altered immune microenvironment. However, metabolic alterations were model-dependent: PD-AS cells shifted toward glycolysis and purine salvage, while U87MUT cells retained oxidative phosphorylation, potentially due to D2-hydroxyglutarate (2OHG)-mediated HIF1A stabilization. We also observed a predominance of downregulated DNA repair proteins in IDH1MUT models, particularly those involved in homologous recombination. In contrast, RB1 and ASMTL were strongly upregulated in both IDH1MUT models, implicating them in DNA repair and cellular stress responses. We also found distinct expression patterns of proteins regulating histone methylation in IDH1MUT cells, favoring increased methylation of H3K4, H3K9, and H3K36. A key driver of this may be the upregulation of SETD2 in PD-AS, an H3K4 and H3K36 trimethyltransferase linked to the recruitment of HIF1A as well as DNA mismatch repair proteins. This study uncovers candidate biomarkers and pathways relevant to glioma progression and therapeutic targeting, but also underscores the complexity of predicting glioma pathogenesis and treatment responses based on IDH1 mutation status. While proteome profiling provides valuable insights, a comprehensive understanding of IDH1MUT gliomas will likely require integrative multi-omics approaches, including DNA/RNA methylation profiling, histone and protein post-translational modification analyses, and targeted DNA damage and repair assays.

• Skuland, Trine; Fosslie, Madeleine Lystad; Khodeer, Sherif; Alemu, Endalkachew Ashenafi; Johansen, Jens Vilstrup & Indahl, Marie [Vis alle 12 forfattere av denne artikkelen] (2025). Broad H3K4me3 domains support oocyte genome silencing and maturation but are dispensable for repression in early embryos. Development. ISSN 0950-1991. 152(21), s. 1–15. doi: 10.1242/dev.204638. Fulltekst i vitenarkiv Vis sammendrag

  Epigenetic reprogramming and embryonic genome activation (EGA) are crucial events during early development. Establishment of distinctive broad histone H3 lysine 4 trimethylation (H3K4me3) domains in the oocyte is necessary for genome silencing, and their removal in the 2-cell embryo is crucial for EGA and development in mice. However, the stage-specific requirement for broad H3K4me3 domains is unclear. Here, we show that inducing broad H3K4me3 removal in mouse oocytes can relieve genome silencing, impair oocyte maturation timing, and may cause transcriptional reactivation in resulting parthenogenetic 1-cell embryos. We further demonstrate that broad H3K4me3 demethylation precedes EGA but, surprisingly, premature depletion in zygotes or early 2-cell embryos does not alter the transcriptional program. Our findings suggest that broad H3K4me3 domains are required for oocyte genome silencing, timely maturation and post-fertilisation silencing, but onward pre-EGA transcriptional repression is not dependent on the original mark. This work contributes to the understanding of events and mechanisms involved in genome silencing and activation in early development, providing insight into potential modes of failure that may contribute to infertility.

• Angheluta, Luiza; Lång, Anna Ulrika; Lång, Emma & Bøe, Stig Ove (2025). Full-Integer Topological Defects in Polar Active Matter: From Collective Migration to Tissue Patterning. Annual Review of Condensed Matter Physics. doi: 10.1146/annurev-conmatphys-031620-105420. Fulltekst i vitenarkiv Vis sammendrag

  Polar active matter—including animal herds, aggregates of motile cells, and active colloids—often forms coordinated migration patterns, such as flocking. This orderly motion can be disrupted by full-integer topological defects representing localized disturbances in which directional alignment is lost. Such polar defects can serve as key organizing centers across scales, sustaining collective behavior such as swirling motion and other large-scale coherent states. Although significant progress has been made in understanding active matter principles in recent years, a quantitative understanding of how topological defects influence active polar matter is still needed. We present a brief overview of recent experimental observations in synthetic active colloids and various biological systems. We describe how polar defects mediate dynamical transitions and contribute to the spontaneous emergence of large-scale coherent states. We also discuss theoretical advances in the physical modeling of coupled processes involving polar defects and collective behavior in active polar matter.

• Berrocal, Marion Silvana Fernández; Døskeland, Dagny Sanden; Saasen, Vidar Langseth; Bugaj, Anna Maria; Kunath, Nicolas & Heggedal, Mina [Vis alle 12 forfattere av denne artikkelen] (2025). NEIL3 shapes hippocampal network dynamics and fear memory through modulation of PV+ interneurons. Progress in Neurobiology. ISSN 0301-0082. 253. doi: 10.1016/j.pneurobio.2025.102832. Fulltekst i vitenarkiv Vis sammendrag

  The dynamic balance between excitatory and inhibitory (E/I) signaling is critical for hippocampal network function and memory processing. Here, we uncover a novel role for the DNA glycosylase Endonuclease VIII-like 3 (NEIL3) in maintaining this E/I balance through its impact on parvalbumin-positive (PV⁺) GABAergic interneurons. NEIL3 deficiency leads to a selective reduction in PV⁺ interneurons and impaired perineuronal net (PNN) integrity, likely contributing to further PV⁺ neuron dysfunction. These changes result in altered hippocampal oscillatory dynamics, including increased beta and low gamma power, and reduced high gamma and ripple activity. These network alterations are accompanied by distinct effects on fear memory, as demonstrated using contextual and trace fear conditioning paradigms. NEIL3-deficient mice exhibited enhanced extinction of contextual fear memory but impaired extinction of trace fear memory. These findings suggest that the integrity of inhibitory networks plays differential roles in the spatial versus temporal aspects of fear memory extinction. Transcriptomic analysis further reveals dysregulation of genes involved in glutamatergic and GABAergic signaling. Among these, Gabra2 showed a marked downregulation, potentially driven by changes in promoter DNA methylation. This work identifies NEIL3 as an important regulator of the hippocampal inhibitory network, linking PV+ interneuron integrity and oscillatory coordination to distinct memory outcomes, and offers potential mechanistic insight into processes that may contribute to cognitive deficits in disorders characterized by E/I imbalance.

• Arczewska, Katarzyna D; Sys, Dorota; Nilsen, Hilde L & Piekiełko-Witkowska, Agnieszka (2025). DNA Damage and Repair in Thyroid Physiology and Disease. Endocrine reviews. ISSN 0163-769X. 47(1), s. 121–157. doi: 10.1210/endrev/bnaf035. Fulltekst i vitenarkiv Vis sammendrag

  The thyroid is exposed to DNA damage induced by normal physiological processes (eg, oxidative stress resulting from thyroid hormone synthesis or mitochondrial respiration) or through environmental insults (eg, environmental pollutants, ionizing radiation exposure). Robust antioxidative stress defense and DNA repair mechanisms protect thyrocyte genome integrity, but defective or dysregulated DNA repair pathways have been implicated in thyroid pathology, including autoimmune thyroid disease and thyroid malignancy. In thyroid cancer, disturbed antioxidative stress defense, Mismatch Repair, Non-Homologous End-Joining, or DNA damage response pathways contribute to both the onset and progression of the disease. The insight into mechanisms governing thyrocyte genome integrity may help to gain better understanding of the pathology and suggest novel therapeutic regimens, urgently needed in treatment-refractory disease. In the current review, we provide comprehensive description of the exogenous and endogenous factors, as well as DNA repair mechanisms influencing thyrocyte genome integrity. Moreover, we pinpoint major research avenues that should be pursued in future research. This information will be valuable in directing new discoveries to better understand thyroid disease pathomechanisms, as well as aid development of novel diagnostic and therapeutic tools.

• Bø, Ragnhild; Jonassen, Rune; Harmer, Catherine; Øverli, Øyvind; Nilsen, Hilde & Esbensen, Qin Ying [Vis alle 13 forfattere av denne artikkelen] (2025). 5-HTTLPR does not moderate the effect of attention bias modification for depression: a randomized sham-controlled trial. Translational Psychiatry. 15, s. 1–6. doi: 10.1038/s41398-025-03581-3. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The 5-HTTLPR polymorphism in the serotonin transporter gene SLC6A4 has previously been dubbed a plasticity marker. Within the 5-HTTLPR polymorphism, a SNP (rs25531) in the L-allele in the promoter region, affects the transcription efficacy of the SCL6A4 , leading to functionally important differences related to serotonin transporter availability in the synapses. 5-HTTLPR has been implicated in magnitude of negative attentional bias, a causal risk factor for depression, and the modifiability of attentional biases both in positive and negative directions. Hence, this genotype may moderate the outcomes of attention bias modification (ABM) targeted at reducing depressive symptoms. We conducted a registered randomized sham-controlled trial of ABM in a sample of 301 participants with a history of Major Depressive Disorder (MDD) who had residual symptoms. They were randomized and underwent 14 days of two daily session of either ABM or sham at home. Of these, 264 provided genetic samples for determining the functionally important variant of the gene SLC6A4 . We investigated if the SNP ( rs25531 ) moderated the effect of ABM on symptoms of depression (HDRS, BDI-II) and anxiety (BAI), and attention bias post-intervention. None of the outcomes were moderated by the allelic variation in the promoter region of 5-HTTLPR . Limitations include low level of depressive symptoms, lack of data on ethnicity, current and prenatal level of stress, and early traumatic experiences. The 5-HTTLPR polymorphism did not moderate the effect of ABM on the symptom scales, nor attentional bias. Combination or interactions with other genes may be required for prescribing personalized interventions.

• Rudolfova, Natalie; Skjetne, Alexander Myhr; Montaldo, Nicola Pietro; Visnes, Torkild; Nilsen, Hilde & Michel, Maurice (2025). What is in a name? Rethinking SMUG1 in genome maintenance. NAR Cancer. 7(4), s. 1–12. doi: 10.1093/narcan/zcaf050. Fulltekst i vitenarkiv Vis sammendrag

  Small base lesions in DNA are primarily repaired through the base excision repair pathway, which is initiated by DNA glycosylases. This review focuses on single-strand selective monofunctional uracil–DNA glycosylase (SMUG1), an enzyme whose name incompletely captures its broader biological roles. SMUG1 excises a wide range of substrates beyond uracil, shows a preference for double-stranded DNA, and has been reported to be a bifunctional DNA glycosylase with a weak lyase activity. Moreover, SMUG1 plays roles extending beyond DNA repair, including functions in RNA quality control and RNA biogenesis. Recently, genetic interactions have been described between SMUG1 and proteins that safeguard stressed replication forks, implicating a function for SMUG1 in cancer cell biology. Understanding SMUG1’s full repertoire is key to uncovering its role in genome maintenance and unlocking its potential as a therapeutic target. Here, we review the biochemical properties reported for SMUG1 and its distinct functions from other uracil–DNA glycosylases in vivo. We also highlight the emerging role of SMUG1 in cancer cells and its potential as a therapeutic target, emphasizing the need to define the genetic and molecular contexts in which its modulation may be beneficial.

• Fosslie, Madeleine Lystad; Ilaslan, Erkut; Skuland, Trine; Choudalakis, Michel; Søegaard, Mirra Louise Cicilie & Halliwell, Jason Alexander [Vis alle 23 forfattere av denne artikkelen] (2025). Major waves of H2A.Z incorporation during mouse oogenesis and preimplantation embryo development. Nature Communications. 17(1). doi: 10.1038/s41467-025-66919-x. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Epigenomes of mammalian oocytes and embryos undergo major transitions essential for successful development. Here, we provide genome-wide maps of histone variant H2A.Z during twelve stages of mouse oogenesis and preimplantation embryo development and relate it to histone marks and genomic features. This revealed that major waves of H2A.Z incorporation occur early in growing oocytes, forming distinct patterns of maternal, embryonic, and persistent H2A.Z enrichment. Late maternal enrichment is inherited by the zygote and precedes reduced formation of lamina associated domains and early replication in the maternal genome of 2-cell embryos. Persistent H2A.Z enrichment is strongly associated with CpG islands and H3K4me3 near transcription start sites of active genes, but thousands of maternal and embryonic H2A.Z incorporation sites exist elsewhere, frequently at transposable elements. The persisting H2A.Z enrichments across related developmental stages enable preservation of epigenetic information despite major concurrent changes in H3K4me3, H3K27me3, and DNA methylation. Altogether, this advances our understanding of how histone variants contribute to epigenetic reprogramming during mammalian oogenesis and early development.

• Kissova, Miroslava; Segarra, Judit Martinez; Iveland, Tobias Solli; Vestvik, Marthe; Ravlo, Erlend & Wang, Wei [Vis alle 17 forfattere av denne artikkelen] (2025). RNaseH2 inhibition potentiates temozolomide response in patient derived glioblastoma cells. Scientific Reports. 15, s. 1–12. doi: 10.1038/s41598-025-25298-5. Fulltekst i vitenarkiv Vis sammendrag

  Glioblastoma (GBM) is the most common and lethal form of primary brain tumor, characterized by poor prognosis and limited treatment options, with a median survival of only 12 to 15 months post-diagnosis. Despite standard therapeutic protocols involving temozolomide (TMZ) and radiotherapy, effective treatment is challenging, underscoring the need to explore alternative therapeutic strategies. One promising approach is the inhibition of DNA damage response (DDR) pathways. RNaseH2, a key enzyme involved in ribonucleotide excision repair (RER), plays a critical role in maintaining genomic stability by removing ribonucleotides misincorporated into DNA. Thus, inhibition of RNaseH2 may enhance tumor mutational burden (TMB) and potentially transform immunogenically “cold” tumors into immunogenically “hot” tumors. In this study, a high-throughput screening (HTS) assay resulted in the identification of 52 potential RNaseH2 inhibitors from a library of 71227 compounds. We selected six of these inhibitors for further investigation, evaluating their effects both alone and in combination with TMZ in commercially available U87 MG wild-type and IDH1 mutant (IDH1 WT and MUT) glioma cells and patient-derived cells established from glioma organoids (GBO-PDC). This study highlights the therapeutic potential of RNaseH2 inhibition in combination with TMZ for GBM therapy, validated in patient-derived model, offering a promising avenue for treating this highly aggressive and yet uncurable cancer.

• Alsøe, Lene; Brackmann, Stephan Andreas; Lefol, Yohan Pierre; Wennerström, Anna Berit; Liu, Yan & Riques, Rosa Ana [Vis alle 8 forfattere av denne artikkelen] (2025). Colonic Mucosal Gene Expression Profile in Patients with Neoplastic Progression in Longstanding Ulcerative Colitis. Clinical and Experimental Gastroenterology. 18, s. 215–232. doi: 10.2147/ceg.s528854. Fulltekst i vitenarkiv
• Anwer, Danish; Montaldo, Nicola Pietro; Novoa-del-Toro, Elva Maria; Domanska, Diana; Nilsen, Hilde Loge & Polster, Annikka Virginia (2025). Longitudinal assessment of DNA repair signature trajectory in prodromal versus established Parkinson’s disease. NPJ Parkinson's Disease. 11(1). doi: 10.1038/s41531-025-01194-7. Fulltekst i vitenarkiv Vis sammendrag

  Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. DNA repair dysfunction and integrated stress response (ISR) dysregulation have been suggested to be relevant in PD pathophysiology, but their role during the prodromal phase, before motor symptoms manifest, remains unclear. In this study, we analyzed longitudinal blood transcriptomic data from the Parkinson’s Progression Markers Initiative (PPMI) to investigate how DNA repair and ISR gene expression differ across healthy individuals, prodromal PD patients, and individuals with established PD. Using logistic regression classifiers, a type of supervised machine learning model, we found that DNA repair and ISR gene expression effectively distinguished prodromal PD from healthy individuals, with classification accuracy increasing over time and peaking at later prodromal stages. In contrast, these pathways failed to differentiate established PD from healthy controls, suggesting that DNA repair and ISR dysregulation play a more distinct role early in disease progression. Gene expression variability was high in prodromal PD at baseline but reduced over time, indicating a convergence in gene expression patterns as the disease advances. Notably, 50% of DNA repair genes and 74% of ISR genes exhibited nonlinear expression patterns, with an initial increase followed by a decline. This suggests a transient adaptive response that fades out as PD progresses. Feature importance analysis identified key genes, including ERCC6, PRIMPOL, NEIL2, and NTHL1, as important predictors of prodromal PD. These findings suggest that DNA repair and ISR dysregulation contribute to early-stage PD pathology and may serve as biomarkers for early disease detection and possible treatment avenues during the prodromal phase. This study highlights the role of DNA repair and ISR pathways in the prodromal phase of PD, demonstrating their potential as early molecular indicators of disease onset. Future research should validate these findings in larger cohorts and explore their relevance for early diagnostics and intervention strategies.

• Schroer, Lisa; Weirich, Sara; Hammerstad, Marta; Hersleth, Hans-Petter; Grønsberg, Ida Andrietta & Hagen, Lars [Vis alle 11 forfattere av denne artikkelen] (2025). Orthologues of the human protein histidine methyltransferase METTL9 display distinct substrate specificities. Journal of Biological Chemistry. ISSN 0021-9258. 301(7). doi: 10.1016/j.jbc.2025.110318. Fulltekst i vitenarkiv Vis sammendrag

  The human (Homo sapiens; Hs) methyltransferase (MTase) METTL9 is the first enzyme shown to generate 1-methylhistidine (π-methylhistidine) in proteins. METTL9 preferentially methylates an alternating histidine (HxH) motif, where “x” is a small, uncharged amino acid, and multiple substrates have been identified. Putative METTL9 orthologues are found in most eukaryotes, and we have here investigated the activity of such enzymes from several species, representing all five eukaryotic supergroups. The majority of the tested enzymes demonstrated in vitro MTase activity on the prototype HsMETTL9 substrates ARMC6 and DNAJB12. We also detected protein methylation activity of the Caenorhabditis elegans METTL9 which had previously been suggested to be a DNA MTase. However, METTL9 from the fruit fly (Drosophila melanogaster; Dm) and the picoplankton Ostreococcus tauri (Ot) displayed distinct substrate specificities, differing from each other and from that of HsMETTL9. These differences were observed when recombinant proteins and short peptides were used as METTL9 substrates. To further analyze substrate specificity, we used peptide arrays to systematically replace the “x” residue and the residues flanking the HxH motif in a substrate peptide. This revealed varying degrees of tolerance among the METTL9 orthologues (Hs > Dm > Ot) for substitutions at these positions. Our results show that the METTL9 orthologues, although requiring an HxH target site, have evolved different substrate specificities, likely due to differing biologically relevant substrates in the respective organisms. Furthermore, we solved the X-ray structure of OtMETTL9, revealing several differences from the previously published HsMETTL9 structures that may explain its distinct substrate specificity.

• Malecki, Jedrzej Mieczyslaw; Weirich, Sara; Ramirez, Manuel; Hagen, Lars; Al-Egly, Jakin Saad & Anonsen, Jan Haug [Vis alle 12 forfattere av denne artikkelen] (2025). Identification of substrates and sequence requirements for CARNMT1-mediated histidine methylation of C3H zinc fingers. Journal of Biological Chemistry. ISSN 0021-9258. 301(7). doi: 10.1016/j.jbc.2025.110335. Fulltekst i vitenarkiv Vis sammendrag

  It has recently become clear that protein histidine methylation is widespread and functionally important in many cellular processes, and human CARNMT1 was recently reported as a novel protein histidine methyltransferase (HMT). We describe our independent uncovering of CARNMT1's protein HMT activity and a comprehensive assessment of its methylation targets and substrate specificity. Using a combination of in vitro methylation of cellular extracts and protein mass spectrometry, we identified several CARNMT1 substrates that were fully methylated in cells, all of which were C3H zinc finger (ZnF) proteins. These include the previously identified U2AF1, ZC3H15, and ZC3H18 but also the unreported RBM22, PPP1R10, PRR3, and RNF113A. Using peptide arrays, we investigated CARNMT1-mediated methylation of 145 candidate sequences, encompassing all C3H ZnFs and selected non-ZnFs. We found that only ∼30% of the tested sequences were methylated, with C3H ZnFs constituting the vast majority of the strongly methylated ones, most of which are also methylated in cells. This establishes peptide methylation as a good predictor of in vivo methylation. To investigate the specificity of CARNMT1, we systematically substituted His-proximal residues in four different substrate peptides. This generated four rather different sequence preference profiles, which were still quite restrictive for each peptide, indicating that substrate sequence recognition by CARNMT1 is context-dependent and that sequence-based prediction of additional CARNMT1 substrates may be challenging. We also identified several homologous methylation events in Caenorhabditis elegans and showed that they could be introduced by nematode CARNMT in vitro. Thus, CARNMT1 is an evolutionarily conserved protein HMT with a complex mode of substrate recognition.

• Desgarnier, Marie-Catherine Anne Danielle Drigeard; Monshaugen, Ida; Ougland, Rune & Klungland, Arne (2025). The 6-methyladenine erasers ALKBH5 and FTO influence chemotherapy efficiency in bladder cancer cell lines. Annals of Translational Medicine. ISSN 2305-5839. 13(3). doi: 10.21037/atm-25-7. Fulltekst i vitenarkiv
• Luan, Yan; Zhang, Hanyue; Liu, Yingfei; Zhou, Jing; Li, Wen & Ma, Kaige [Vis alle 14 forfattere av denne artikkelen] (2025). Inverse and dynamic levels of H3K4me3 and H3K27me3 regulate mouse postnatal dental gyrus development. Cell Death and Differentiation. ISSN 1350-9047. 33, s. 219–235. doi: 10.1038/s41418-025-01563-y. Fulltekst i vitenarkiv Vis sammendrag

  The dentate gyrus (DG), a crucial region of the hippocampus responsible for learning, spatial encoding, and memory formation, undergoes its main development and maturation after birth. Despite its importance, the regulatory mechanisms underlying postnatal DG development remain poorly understood. Thi …

• Zhang, Jianying; Wang, Heling; Lautrup, Sofie Hindkjær; Nilsen, Hilde; Treebak, Jonas T. & Watne, Leiv Otto [Vis alle 28 forfattere av denne artikkelen] (2025). Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging. 5(9), s. 1704–1731. doi: 10.1038/s43587-025-00947-6. Fulltekst i vitenarkiv Vis sammendrag

  Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

• Bordin, Diana Lilian; Lefol, Yohan Pierre; Lagartos, Maria Jose Donate; Montaldo, Nicola Pietro; Rolseth, Veslemøy & Tekin, Nuriye Basdag [Vis alle 18 forfattere av denne artikkelen] (2025). SMUG1 DNA glycosylase modulates reward behaviour through regulation of olfactory receptor gene expression. Nucleic Acids Research (NAR). ISSN 0305-1048. 53(14). doi: 10.1093/nar/gkaf722. Fulltekst i vitenarkiv
• Dufour, Damien; Zhao, Xu; Chaleil, Florian; Nothnagel, Patrizia Maria Christiane; Bjørås, Magnar & Lefrançois-Martinez, Anne-Marie [Vis alle 8 forfattere av denne artikkelen] (2025). Pharmacological inhibition of SUMOylation with TAK-981 mimics genetic HypoSUMOylation in murine perigonadal white adipose tissue. Adipocyte. ISSN 2162-3945. 14(1). doi: 10.1080/21623945.2025.2474107. Fulltekst i vitenarkiv Vis sammendrag

  Post-translational modification by the small ubiquitin-like modifier (SUMO) is essential for cellular differentiation and homeostasis. Here, we investigate the role of SUMOylation in adipose tissue development using TAK-981, a pharmacological inhibitor of SUMOylation. Administration of TAK-981 to mice resulted in significant defect in weight gain and adipocyte atrophy in perigonadal white adipose tissue (gWAT) depots. Gene expression analyses revealed a marked downregulation of adipogenic genes, including Pparg, Cebpa, and Fasn. Our data thus indicate that TAK-981 treatment impaired adipogenesis in gWAT, consistent with prior findings that SUMOylation supports transcriptional regulation of adipogenesis and lipid metabolism. We also found significant infiltration of immune cells and efferocytosis in gWAT. Our results thus indicate that SUMOylation inhibition using a small molecule phenocopies genetic hypoSUMOylation models, highlighting its critical role in maintaining adipocyte functionality and immune environment. These findings provide evidence that SUMOylation is essential for fat accumulation in vivo. Furthermore, given that TAK-981 is currently under clinical evaluation for the treatment of solid tumors, our results underscore the importance of considering the potential unintended effects of SUMOylation inhibition on adipose tissue in patients.

• Dragland, Jenny Sofie; Liu, Gege; Nilsen, Hilde; Böttcher, Yvonne & Wang, Junbai (2025). EpiMapper: A new tool for analyzing high-throughput sequencing from CUT&Tag. Computers in Biology and Medicine. ISSN 0010-4825. 186. doi: 10.1016/j.compbiomed.2025.109692. Fulltekst i vitenarkiv Vis sammendrag

  Since the invention of next-generation sequencing, new methods have been developed to understand the regulation of gene expression through epigenetic markers. Among these, CUT&Tag (Cleavage Under Targets and Tagmentation) analysis has emerged as an efficient epigenomic profiling technique with low input requirements, high sensitivity, and low background signals. Although wet-lab techniques are available, data analysis remains challenging for scientists without expert-level computational skills. Therefore, we developed EpiMapper, a new Python package that simplifies the data analysis of CUT&Tag sequencing and similar techniques, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) or ChIP-seq (chromatin immunoprecipitation [ChIP] assays with sequencing), and allows biomedical scientists to easily interpret the results. This new package includes every necessary step, from quality control to annotation and differential peak analysis. In particular, EpiMapper has improved functionality (e.g., reproducibility assessment) compared to previous analysis protocols and visualization plots and provides new features, such as genome annotation and differential peak analysis. Using three case studies, two on CUT&Tag and one on ATAC-seq data, the EpiMapper Python package successfully reproduced previous results.

• Abentung, Andreas; Sakshaug, Teri; Dumaru, Rabina; Liabakk, Nina-Beate; Yang, Mingyi & Wang, Junbai [Vis alle 8 forfattere av denne artikkelen] (2025). DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 82. doi: 10.1007/s00018-025-05730-9. Fulltekst i vitenarkiv Vis sammendrag

  Base excision repair, initiated by DNA glycosylases, preserves genomic integrity by removing damaged bases. DNA glycosylases Ogg1 and Mutyh were shown to alter the hippocampal transcriptome independently of DNA damage repair. However, the role of DNA glycosylases as transcriptional regulators and their involvement in cognition remain unclear. Here, we combine transcriptomic and epigenomic analyses of the hippocampus in mice deficient in DNA glycosylases. We report that the combined deficiency of Ogg1 and Mutyh impairs spatial long-term memory. Mechanistically, Ogg1 and Mutyh modulate DNA methylation of polycomb repressive complex 2 (PRC2) target genes. PRC2 occupancy and associated histone post-translational modifications depend on Ogg1 and Mutyh in neurons and glia. These epigenetic changes correlate with cell-type specific differences in gene expression of PRC2 targets. Finally, human genetic data link DNA glycosylase-regulated genes to cognitive function, highlighting a novel role for Ogg1 and Mutyh in modulating the epigenome to control transcriptional responses relevant for brain-related diseases.

• Lobie, Tekle Airgecho; Krog, Charlotte Solum; Skarstad, Kirsten; Bjørås, Magnar & Booth, James Alexander (2025). Escherichia coli type I toxin TisB exclusively controls proton depolarization following antibiotic induced DNA damage. Scientific Reports. 15(1). doi: 10.1038/s41598-025-96136-x. Fulltekst i vitenarkiv Vis sammendrag

  Bacterial toxin-antitoxin (TA) systems are genetic loci where the antitoxin gene product helps to control the expression or activity of the toxin gene product. Type I TA systems typically produce hydrophobic peptides that often localize to the inner membrane of bacteria. These amphipathic peptides can then potentially affect ion flows across the inner membrane. Here, we show that several type I toxins from Escherichia coli can affect depolarization, whereas tisB exclusively controls the depolarization of the proton gradient. tisB has been linked to persister cell formation following treatment with the antibiotic ciprofloxacin and tisB-istR has been implicated in the control of proton depolarization following treatment with ofloxacin. These results suggest that tisB could initiate the formation of persister cells by fully dissipating the proton gradient and that most of the electrical gradient greatly limiting ATP production following antibiotic-induced DNA damage.

• Montaldo, Nicola Pietro; Nilsen, Hilde & Bordin, Diana Lilian (2025). Targeting base excision repair in precision oncology. DNA Repair. ISSN 1568-7864. 149. doi: 10.1016/j.dnarep.2025.103844. Fulltekst i vitenarkiv Vis sammendrag

  Targeting the DNA damage response (DDR) is a key strategy in cancer therapy, leveraging tumour-specific weaknesses in DNA repair pathways to enhance treatment efficacy. Traditional treatments, such as chemotherapy and radiation, use a broad, damage-inducing approach, whereas precision oncology aims to tailor therapies to specific genetic mutations or vulnerabilities. The clinical success of PARP inhibitors has renewed the interest in targeting DNA repair as a therapeutic strategy. Expanding the precision oncology toolbox by targeting the base excision repair (BER) pathway presents a promising avenue for cancer therapy, particularly in tumours that rely heavily on this pathway due to deficiencies in other DNA repair mechanisms. This review discusses how targeting BER could improve treatment outcomes, particularly in DDR-defective cancers. With ongoing advancements in biomarker discovery and drug development, BER-targeted therapies hold significant potential for refining precision oncology approaches.

• Iveland, Tobias Solli; Hagen, Lars; Sousa, Mirta; Liabakk, Nina-Beate; Aas, Per Arne & Sharma, Animesh [Vis alle 8 forfattere av denne artikkelen] (2025). Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA. Scientific Reports. 15(1). doi: 10.1038/s41598-025-86007-w. Fulltekst i vitenarkiv Vis sammendrag

  The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers. Proteomic alterations were analyzed using label-free shotgun and targeted LC–MS/MS. MS275 enhanced the sensitivity of A549 cells to pemetrexed, but only when administered following prior treatment with pemetrexed. Both HeLa (p53 negative) and A549 (p53 positive) showed robust activation of γH2AX upon treatment with this combination. Importantly, CRISPR/Cas9 knockout of the uracil-DNA glycosylase UNG did not affect γH2AX activation or sensitivity to pemetrexed. Proteomic analysis revealed that MS275 altered the expression of known pemetrexed targets, as well as several proteins involved in pyrimidine metabolism and DNA repair, which could potentiate pemetrexed cytotoxicity. Contrary to the conventional model of antifolate toxicity, which implicates futile cycles of uracil incorporation and excision in DNA, we propose that ribonucleotide incorporation in nuclear and mitochondrial DNA significantly contributes to the cytotoxicity of antifolates like pemetrexed, and likely also of fluorinated pyrimidine analogs. HDAC inhibition apparently exacerbates cytotoxicity of these agents by inhibiting error-free repair of misincorporated ribonucleotides in DNA. The potential of HDACis to modulate pyrimidine metabolism and DNA damage responses offers novel strategies for improving NSCLC outcomes.

• Yildirim, Zuleyha; Noll, Aurélia; Martin-Hernandez, Kathline; Amé, Jean-Christophe; Hanini, Najat & Messaddeq, Nadia [Vis alle 11 forfattere av denne artikkelen] (2025). Parp3 assists muscle function and skeletal muscle differentiation by selectively adjusting H3K27me3 enrichment. iScience. 28(4). doi: 10.1016/j.isci.2025.112267. Fulltekst i vitenarkiv Vis sammendrag

  Poly(ADP-ribose) polymerase 3 (Parp3) is known for its role in DNA repair, mitotic division, and cancer aggressiveness. Still, its physiological roles have yet to be defined. Here, we combined in vivo studies using Parp3-deficient mice with in cellulo studies to explore the involvement of Parp3 in skeletal muscle function and muscle differentiation. We show that Parp3 contributes to skeletal muscle integrity and promotes myogenic differentiation. Mechanistically, we show that Parp3 promotes the enrichment of the repressive histone mark H3K27me3 onto a panel of selected genes. For some genes, Parp3 also helps the binding of Ezh2, the histone methyltransferase that catalyzes H3K27me3. Moreover, Parp3 ADP-ribosylates Ezh2 in vitro. Altogether, these findings unveil Parp3 as a driver of efficient murine skeletal myogenesis in vitro and muscle function in young adults, and highlight an epigenetic control of gene expression.

• Li, Yanjiao; Wang, Yunhao; Cengiz, Aylin; Jin, Kangxuan; castroviejo, Blanca Corral & Lin, Xiaolin [Vis alle 19 forfattere av denne artikkelen] (2025). The RNA m6A landscape during human oocyte-to-embryo transition. EMBO Journal. ISSN 0261-4189. 44(14), s. 4150–4180. doi: 10.1038/s44318-025-00474-5. Fulltekst i vitenarkiv Vis sammendrag

  RNA N6-methyladenosine (m6A, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic m6A profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA m6A landscape of single human oocytes and early embryos. Comparative analyses with mouse data reveal an intriguing divergence during the window of zygotic genome activation. m6A-modified genes are involved in regulation of gene transcription, while unmodified genes are mainly associated with basic metabolic processes. Maternal decay mRNAs exhibit a propensity for m6A modifications, and these genes are targeted by miRNAs. m6A modified genes that are constantly expressed across all stages demonstrate higher translation efficiency. Moreover, we observe frequent m6A enrichment on stage-specifically expressed retrotransposons, particularly within young subfamilies. m6A inhibitor leads to m6A erasure on massive retrotransposons. In summary, this study provides a resource to broaden our understanding about the regulatory roles of m6A during early human embryo development.

• Ianevski, Aleksandr; Quilez, Maria Camara; Wang, Wei; Suganthan, Rajikala; Hildrestrand, Gunn Annette & Grini, Jonas Viken [Vis alle 9 forfattere av denne artikkelen] (2025). Early transcriptional responses reveal cell type-specific vulnerability and neuroprotective mechanisms in the neonatal ischemic hippocampus. Acta neuropathologica communications. 13(1). doi: 10.1186/s40478-025-02062-4. Fulltekst i vitenarkiv Vis sammendrag

  Neonatal hypoxic-ischemic (H-I) brain injury, a leading cause of neurodevelopmental disabilities, severely affects the metabolically active and neurogenic hippocampus. To investigate its acute effects and identify drug targets for early therapeutic windows, we applied single-nucleus RNA sequencing on postnatal day 8 (P8) mouse hippocampi under sham, hypoxic, and hypoxic-ischemic conditions. We constructed a comprehensive hippocampal cell atlas and developed a machine-learning classifier for precise cell type identification. Our analysis reveals early vulnerabilities in mature neurons and notable resilience in immature DG, GABAergic, and Cajal-Retzius cells following H-I. Gene regulatory network analysis identified key transcription factors associated with neuronal vulnerability, along with upregulated ribosome biogenesis and dysregulated calcium homeostasis pathways. We observed rapid activation of astrocytes and microglia, with Runx1 identified as a potential key transcription factor associated with early microglia immune responses. Endothelial cells displayed complex transcriptional changes and predicted intercellular signaling patterns that may influence vascular repair and recovery. Our study advances the understanding of immediate cellular and transcriptional responses to neonatal H-I injury, providing new insights into hippocampal cell heterogeneity and pathophysiology. The integrated hippocampal atlas, post-H-I atlas, and machine learning classifier are available at https://hippo-seq.org.

• Ravlo, Erlend; Ianevski, Aleksandr; Skipperstøen, Marius Nårstad; Lysvand, Hilde; Schjølberg, Jørn-Ove & Solheim, Ole Skeidsvoll [Vis alle 20 forfattere av denne artikkelen] (2025). JAK inhibitors remove innate immune barriers facilitating viral propagation. NAR Molecular Medicine. 2(2). doi: 10.1093/narmme/ugaf017. Fulltekst i vitenarkiv
• Chen, Xiufei; Cheng, Jingfei; Kong, Linzhen; Shu, Xiao; Xu, Haiqi & Inoue, Masato [Vis alle 13 forfattere av denne artikkelen] (2025). Direct and bisulfite-free 5-methylcytosine and 5-hydroxymethylcytosine sequencing at single-cell resolution with scTAPS and scCAPS + . Genome Biology. ISSN 1465-6906. 26(1). doi: 10.1186/s13059-025-03708-1. Fulltekst i vitenarkiv
• Ravlo, Erlend; Ianevski, Aleksandr; Schjølberg, Jørn-Ove; Solvang, Vanessa; Dumaru, Rabina & Lysvand, Hilde [Vis alle 31 forfattere av denne artikkelen] (2025). Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 82. doi: 10.1007/s00018-025-05581-4. Fulltekst i vitenarkiv Vis sammendrag

  Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally available, safe-in-man pleconaril, AG7404, and mindeudesivir, that at non-toxic concentrations effectively inhibited enterovirus replication in human cell and organoid cultures. Importantly, the cocktail did not alter glucose and insulin levels in the culture medium of pancreatic β-cells and preserved the contraction rhythm of infected heart organoids. These findings highlight a promising drug cocktail for further preclinical studies and clinical trials targeting a broad range of enterovirus-mediated diseases.

• Lefol, Yohan Pierre; Hasle, Geir Amund; Hegre, Siv Anita; Samdal, Helle & Sætrom, Pål (2025). Using pseudotime derivative on single-cell RNA sequencing data to identify genes undergoing cell cycle regulation. Bioinformatics Advances. 5(1). doi: 10.1093/bioadv/vbaf123. Fulltekst i vitenarkiv Vis sammendrag

  Motivation: The cell cycle is a critical part of cellular life, one that has long been studied, both directly, and through its regulatory components. Commonly, cell cycle synchronization or selection experiments are performed in order to study the cell cycle, thus chemically modifying the cells, or selecting them for specific phases. We seek to develop a means to study the cell cycle through the use of single cell RNA sequencing, effectively circumventing the need for such experiments. Results: We utilize a well-established pseudotime method, along with the predicted and real expression of genes to calculate the velocity of individual genes. We then utilize statistics and expected biological behaviour to identify genes with significant shifts in velocity within the pseudotime. Additionally, we show the ability to observe gene regulatory behaviour such as mRNA splicing and degradation rates. As many cell line based research utilize multiple replicates we implement a merger method for technical replicates to adjust for technical variations, creating a more robust analysis. In summary, our study develops a robust approach to map the velocities of individual, biologically, and statistically significant genes throughout the cell cycle’s phases within a cell line experiment

• Berrocal, Marion Silvana Fernández; Reis, Amilcar; Rolseth, Veslemøy; Suganthan, Rajikala; Kusnierczyk, Anna & França, Arthur [Vis alle 15 forfattere av denne artikkelen] (2025). NEIL3 influences adult neurogenesis and behavioral pattern separation via WNT signaling. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 82(1). doi: 10.1007/s00018-025-05629-5. Fulltekst i vitenarkiv Vis sammendrag

  Adult neurogenesis in the hippocampus, involving the generation and integration of new neurons, is essential for behavioral pattern separation, which supports accurate memory recall and cognitive plasticity. Here, we explore the role of the DNA repair protein NEIL3 in adult hippocampal neurogenesis and behavioral pattern separation. NEIL3 is required for efficient proliferation and neuronal differentiation of neonatal NSPCs and adult-born NPCs in the hippocampus following a behavioral pattern separation task. NEIL3-depleted mice exhibited a reduced preference for the novel object location, indicating a deficit in pattern separation. NEIL3-deficient adult-born neurons exhibited a significant reduction in mature-like membrane properties, indicating impaired functional maturation. Interestingly, these impairments were not associated with the decreased genomic integrity but with the altered transcriptional regulation of the Wnt signaling pathway. Given the importance of adult neurogenesis in cognitive function, targeting NEIL3 could offer therapeutic potential for addressing age-related hippocampal dysfunction and cognitive decline.

• Bai, Xiangning; Rayner, Simon; Skuggen, Linda Ellevog; Engseth, Kine; Bjørnstad, Pål Marius & Dalland, Marianne [Vis alle 9 forfattere av denne artikkelen] (2025). A preliminary evaluation of a fast, low-cost, and high-throughput nucleic acid extraction method for bacterial microbiota profiling in low-microbial biomass samples. Scientific Reports. 15(1). doi: 10.1038/s41598-024-84682-9. Fulltekst i vitenarkiv Vis sammendrag

  The respiratory tract is colonized with low-density microbial communities, which have been shown to impact human respiratory health through microbiota–host interactions. However, a lack of fast and cost-effective nucleic acid extraction method for low-microbial biomass samples hinders investigation of respiratory microbiota. Here, we performed a pilot study to assess the suitability of the NAxtra nucleic acid extraction protocol for profiling bacterial microbiota in respiratory samples. A small number of nasopharyngeal aspirate (n = 8), nasal swab (n = 8), and saliva samples (n = 8) were collected, nucleic acids were isolated using the NAxtra protocol, and 16 S rRNA gene sequencing was performed to characterize bacterial microbiota, which were compared to the same sample types from previous studies using other protocols. The bacterial composition in nasal and saliva samples were consistent with previous reports. Saliva microbiota was significantly richer than nasal microbiota and varied less among individual samples than nasal microbiota. Bacterial composition in nasal samples was distinct from nasopharyngeal aspirates, but closer to saliva samples. A sequencing depth of 50,000 reads/sample was sufficient for microbiota profiling in low biomass respiratory samples. Our pilot study indicates the potential of the NAxtra protocol for bacterial microbiota characterization of low-microbial biomass samples and supports a more comprehensive study to fully evaluate the value of the NAxtra protocol in microbiota research and clinical diagnostics of respiratory pathogens.

• Mera, Aurora Bernal; Cuminetti, Vincent; Serulla, Marc; Florit, Adrian; Konieczny, Joanna & Golnarnik, Golnaz [Vis alle 12 forfattere av denne artikkelen] (2025). Bone marrow sympathetic neuropathy is a hallmark of hematopoietic malignancies and it involves severe ultrastructural damage. Experimental Hematology & Oncology. 14. doi: 10.1186/s40164-025-00614-x. Fulltekst i vitenarkiv Vis sammendrag

  The hematopoietic stem cell (HSC) niche in the bone marrow (BM) supports HSC function, fate and numbers [1]. Sympathetic fibres innervate the BM and are components of the hematopoietic stem and progenitor cell (HSPC) niche [2]. Neuropathy of the HSPC niche is present and essential for disease development in experimental models of JAK2V617F+ myeloproliferative neoplasms (MPN) and MLL-AF9+ acute myeloid leukemia (AML), and it is present in the BM of human MPN and AML patients [3–6]. Neuropathy contributes to mutant HSC expansion and represents an effective therapeutic target to block disease progression in JAK2V617F+ MPN mice [3]. The sympathomimetic agonist mirabegron restored nestin+ cells and reduced reticulin fibrosis in MPN patients [7]. Here, we show that neuropathy of the HSPC niche emerges in two additional experimental models of hematological disease including pre-leukemic myelopoiesis driven by NRASG12D and lymphoma/lymphoblastic leukemia driven by p53 deletion. Neuropathy involves severe ultrastructural damage in NRASG12D+ mice and AML patients as shown by electron microscopy. When further reinforced chemically, neuropathy has a profound impact on the experimental NRASG12D mouse model, promoting myeloid bias, reducing HSPC numbers and inducing changes in the stem cell microenvironment that include reduced numbers of mesenchymal stromal cells (MSC) and increased presence of morphologically abnormal blood vessels in BM. Together, BM neuropathy is a prevalent factor in hematopoietic malignancies that involves important degradation of sympathetic fibres and contributes to disease in a different manner depending on the driver mutation. This should be taken in consideration in the clinic, given that chemotherapy induces neuropathy of the HSC niche [8] and it is the most frequent first line treatment for AML, acute lymphoblastic leukemia and MPN patients.

• Hubers, Lisa Anne; Skjetne, Alexander Myhr; Luna, Luisa; Lefol, Yohan Pierre; Lund, Solveig Osnes & Wågbø, Ane Marit [Vis alle 14 forfattere av denne artikkelen] (2024). Functional Impact of Nth-like DNA glycosylase on Mitochondrial Dynamics. bioRxiv. ISSN 2692-8205. doi: 10.1101/2024.10.10.617535. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT NTH-like DNA glycosylase (NTHL1), a key enzyme in the base excision repair (BER) pathway, has long been considered essential for maintaining both nuclear and mitochondrial genome integrity. In this study, we integrate in vitro biochemical assays, in-cellulo molecular biology experiments, and bioinformatic analyses to investigate the impact of NTHL1 loss on mitochondrial DNA (mtDNA) stability and function. Our findings challenge the conventional view by showing that the loss of NTHL1 confers a positive phenotype. Although NTHL1 deletion in human cells results in a significant accumulation of mtDNA lesions, it is unexpectedly accompanied by a substantial increase in mtDNA copy number (CN), which correlates with elevated oxidative phosphorylation (OXPHOS) protein levels and enhanced mitochondrial respiratory capacity. Additionally, NTHL1-knockout cells exhibit larger mitochondria and increased levels of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and the membrane fusion protein Dynamin-like GTPase OPA1. These changes suggest an adaptive response to stress or altered cellular demands, aimed at enhancing mitochondrial function and capacity. Consequently, NTHL1 -knockout cells showed resistance to 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial stress along with increased phosphorylation of eIF2α. Together, this suggests that the loss of NTHL1 may enhance cellular resilience to oxidative stress by activating protective integrated stress response and mitohormesis pathways thereby contributing to cellular survival under adverse conditions. Collectively, our findings position NTHL1 as a key player in mtDNA stability and mitochondrial function, linking its DNA repair activity to the integrated stress response. Its loss triggers a shift from canonical oxidative phosphorylation to stress-adaptive pathways, ultimately enhancing cellular resistance against oxidative stress through the activation of the mitochondrial hormetic response.

• Obermann, Tobias; Sakshaug, Teri Shearer; Kanagaraj, Vishnu Vignesh; Abentung, Andreas; Sousa, Mirta Mittelstedt Leal de & Hagen, Lars [Vis alle 9 forfattere av denne artikkelen] (2024). Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH. Redox Biology. 79, s. 1–11. doi: 10.1016/j.redox.2024.103461. Fulltekst i vitenarkiv Vis sammendrag

  8-oxo-7,8-dihydroguanine (OG) is one of the most abundant oxidative lesions in the genome and is associated with genome instability. Its mutagenic potential is counteracted by a concerted action of 8-oxoguanine DNA glycosylase (OGG1) and mutY homolog DNA glycosylase (MUTYH). It has been suggested that OG and its repair has epigenetic-like properties and mediates transcription, but genome-wide evidence of this interdependence is lacking. Here, we applied an improved OG-sequencing approach reducing artificial background oxidation and RNA-sequencing to correlate genome-wide distribution of OG with gene transcription in OGG1 and/or MUTYH-deficient cells. Our data identified moderate enrichment of OG in the genome that is mainly dependent on the genomic context and not affected by DNA glycosylase-initiated repair. Interestingly, no association was found between genomic OG deposition and gene expression changes upon loss of OGG1 and MUTYH. Regardless of DNA glycosylase activity, OG in promoter regions correlated with expression of genes related to metabolic processes and damage response pathways indicating that OG functions as a cellular stress sensor to regulate transcription. Our work provides novel insights into the mechanism underlying transcriptional regulation by OG and DNA glycosylases OGG1 and MUTYH and suggests that oxidative DNA damage accumulation and its repair utilize different pathways.

• Falnes, Pål (2024). Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases. Nucleic Acids Research (NAR). ISSN 0305-1048. 52(19), s. 11423–11441. doi: 10.1093/nar/gkae816. Fulltekst i vitenarkiv Vis sammendrag

  Methylation is a common biochemical reaction, and a number of methyltransferase (MTase) enzymes mediate the various methylation events occurring in living cells. Almost all MTases use the methyl donor S-adenosylmethionine (AdoMet), and, in humans, the largest group of AdoMet-dependent MTases are the so-called seven-β-strand (7BS) MTases. Collectively, the 7BS MTases target a wide range of biomolecules, i.e. nucleic acids and proteins, as well as several small metabolites and signaling molecules. They play essential roles in key processes such as gene regulation, protein synthesis and metabolism, as well as neurotransmitter synthesis and clearance. A decade ago, roughly half of the human 7BS MTases had been characterized experimentally, whereas the remaining ones merely represented hypothetical enzymes predicted from bioinformatics analysis, many of which were denoted METTLs (METhylTransferase-Like). Since then, considerable progress has been made, and the function of > 80% of the human 7BS MTases has been uncovered. In this review, I provide an overview of the (estimated) 120 human 7BS MTases, grouping them according to substrate specificities and sequence similarity. I also elaborate on the challenges faced when studying these enzymes and describe recent major advances in the field.

• Romero-Aranda, Cristina; Sáenz-Narciso, Beatriz; Gómez-Orte, Eva; Metola, Ángela; Ezcurra, Begoña & Calvo, Olga [Vis alle 9 forfattere av denne artikkelen] (2024). Integrator complex subunit 6 (INTS-6) mediates DNA damage response in Caenorhabditis elegans. microPublication Biology. s. 1–8. doi: 10.17912/micropub.biology.001345. Fulltekst i vitenarkiv Vis sammendrag

  The Caenorhabditis elegans Integrator complex is a set of at least 13 evolutionarily conserved proteins that binds the C-terminal domain of RNA polymerase II to regulate snRNA 3'-end processing and gene expression. Here we show that the Integrator subunit 6 intervenes in the DNA damage response in C. elegans. We find that upon X-ray radiation, INTS-6 is necessary for RAD-51 foci formation. In addition, CDK-1 Tyr-15 phosphorylation depends on the presence of INTS-6. This work adds a new piece to elucidate the Integrator complex mechanism of action in DNA repair.

Se alle arbeider i NVA

• Cuminetti, Vincent & Arranz, Lorena (2026). Control of acute myeloid leukemia by metabolites. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2026). Exploring the transformation potential of hematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2026). Exploring the transformation potential of human hematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2026). Control of hematopoiesis by Succinate receptor 1 in the stem cell niche. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Knowledge in use: NOK 4,9 million to innovative UiO researchers. [Internet]. /https://www.uio.no/ . doi: https:/www.uio.no/english/about/news-and-events/news/2026/uio-innovation-funds-2026.html. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). ISEH 5th Annual Virtual Career Fair. Fulltekst i vitenarkiv Vis sammendrag

  New Investigators Committee Presents: ISEH 5th Annual Virtual Career Fair Thank you for a successful Career Fair! Are you searching for a new position in the field of hematology? Or are you seeking to recruit talented scientists for your research groups? Join us for the New Investigator Committee virtual career fair! The New Investigator Committee of the International Society for Experimental Hematology (ISEH) is excited to announce our fifth annual FREE virtual career fair. This unique event aims to connect trainees with hiring faculty from around the world. Using a "speed networking" format, hiring faculty will have the chance to engage in one-on-one conversations with individuals currently in the job market. Our goal is to assist trainees in finding valuable training opportunities in hematology labs, while also helping faculty identify talented scientists to join their teams.

• Arranz, Lorena; Carlsten, Mattias & Newman, Rhiannon (2026). Life After YERM: How the Young EHA Research Meeting Shaped Careers. doi: https:/open.spotify.com/episode/0VtPZopANNt1RDlMH3ZaXI. Fulltekst i vitenarkiv
• Arranz, Lorena; Carlsten, Mattias & Newman, Rhiannon (2026). Life After YERM: How the Young EHA Research Meeting Shaped Careers. doi: https:/www.youtube.com/watch?v=VD8eLSrDR1w. Fulltekst i vitenarkiv
• Arranz, Lorena; Cuminetti, Vincent & Doeland, Elin Martine (2026). Vil bekjempe leukemi ved å stoppe stamceller fra å bli til kreftceller. [Internet]. https://www.uio.no/. doi: https:/www.uio.no/forskning/forskningsnytt/artikler/2026/vil-bekjempe-leukemi-stoppe-stamceller-fra-bli-til-kreftceller.html. Fulltekst i vitenarkiv
• Arranz, Lorena; Cuminetti, Vincent & Doeland, Elin Martine (2026). Aim to combat leukaemia by stopping stem cells from becoming cancer cells. [Internet]. /https://www.uio.no/ . doi: https:/www.uio.no/english/research/research-news/articles/2026/aim-to-combat-leukaemia-by-stopping-stem-cells-cancer-cells.html. Fulltekst i vitenarkiv
• Arranz, Lorena & Øksne, Rannveig (2026). 9 millioner til forskning på målrettede blodkreftbehandlinger. [Internet]. https://www.blodkreftforeningen.no/. doi: https:/www.blodkreftforeningen.no/om-oss/nyhetsarkiv/tildeling-neurotarget. Fulltekst i vitenarkiv
• Henriquez, Daniela Cabrera & Arranz, Lorena (2026). Mapping succinate receptor 1 expression and function in the bone marrow niche. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Neuropathy of the stem cell niche in myeloid leukemias – potential for therapeutic targeting. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv Vis sammendrag

  Our research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Our goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies. We will give an overview of our research and present unpublished observations accepted in principle in Nature Communications, where we have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Our work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.

• Arranz, Lorena (2026). Potential for therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv Vis sammendrag

  Lorena Arranz's research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Their goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies. Dr Arranz will give an overview of her research and present their group's recent work, where they have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Their work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.

• Holub, Elina; Jochems, Reina; Zeremichael, Teklu Tewoldebrhan; Klungland, Arne & Kommisrud, Elisabeth (2026). Reduced in vitro maturation time of bovine oocytes may increase blastocyst yield. Fulltekst i vitenarkiv
• Muri, Pia; Wågbø, Ane Marit; Degnes, Kristin Fløgstad; Klinkenberg, Geir; Pandey, Deo Prakash & Visnes, Torkild (2026). Phenotypic drug profiling. doi: https:/www.ntnu.no/kalender/detaljer/-/event/e47637ae-b126-38c8-bfbc-b0f84a93dd55. Fulltekst i vitenarkiv
• Cuminetti, Vincent (2025). What to do when your PhD project doesn’t progress (?). Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Neuropathy of the stem cell niche in myeloid leukemias – potential for therapeutic targeting. Fulltekst i vitenarkiv
• Buer, Sofie; Hagen, Bjørn Ole Ingulfsvann; Søraas, Arne Vasli Lund; White, Richard Aubrey; Lerdal, Anners & Nygaard, Anders Benteson [Vis alle 7 forfattere av denne artikkelen] (2025). Working Memory Deficits in the post-acute phase of COVID-19 in a Clinical Trial Population. doi: https:/event.trippus.net/Home/Index/AEAKgIPHKxDGXt9WWufkKpiqnCz6wQruet7nzC50zg3_S3hAj-XGe9T9NTp47uSsFlG4xbd_zhBm/AEAKgIPGaNFh8o7gPpdTB6e-8t5U-Cs-bMNPVzKOFUzFTeufxZ-sT9BfzwNmJiybZYKgn43Mnh4S/eng. Fulltekst i vitenarkiv
• Kleve, Guro; Santa, Chiara Dalla; Kristiansen, Felicia Iselin Svensson; Tegnander, Marita; Buch, Victoria & Hagemann, Cecilie Steen [Vis alle 29 forfattere av denne artikkelen] (2025). Digital home-based multimodal prehabilitation of colorectal cancer patients prior to surgery (the dHOPE study): a non-inferiority clinical trial protocol. doi: 10.3389/fdgth.2025.1609678. Fulltekst i vitenarkiv Vis sammendrag

  Cancer surgery is associated with risk of complications and loss of function. Vulnerability factors, such as advanced age, malnutrition, smoking, comorbidity, frailty, and low socioeconomic status increase the risk. Lifestyle intervention prior to surgery, known as prehabilitation, often include physical activity, nutritional support, psychological coaching, and smoking cessation, increase functional reserves and reduce postoperative complications. Most importantly, it prevents loss of functional capacity and dependence. Methods The dHOPE study is a three-armed, open-labelled, parallel-group randomized controlled trial (RCT) with non-inferiority design to compare a digital home-based prehabilitation program with a hospital-based program or no organized prehabilitation. In addition, the dHOPE study aims to identify measurable parameters reflecting the effect of prehabilitation, thus preparing for future personalization of the prehabilitation programs. Discussion The feasibility of multimodal prehabilitation is threatened by low compliance to hospital-based programs due to burdensome commuting, even in central and metropolitan areas. In sparsely populated countries, this challenge is even more pronounced. To ensure equal healthcare to all citizens regardless of address or economic situation, there is a need to transfer the prehabilitation program to the patients’ homes. Thus, the primary hypothesis of dHOPE is that a digital home-based program is not inferior to a hospital-based program. Moreover, given the patient diversity, prehabilitation must be personalized to meet individual profiles or needs. An exploratory subtask of dHOPE is to confirm the utility of clinical, genetic, and molecular factors in evaluating prehabilitation response ultimately to identify new biomarkers and develop medical software for individual risk stratification and development of personalized prehabilitation programs. Clinical Trial registration https://clinicaltrials.gov/ , identifier (NCT06231576).

• Haarberg, Odin Weberg; Holland, Petter & Nilsen, Hilde (2025). Kan aldringsbiologien gi oss en ny tilnærming til helse og sykdom? 22(3), s. 219–237. doi: 10.5617/michael.12617. Fulltekst i vitenarkiv Vis sammendrag

  Aldring og helse får stadig mer oppmerksomhet. Medier, ikke minst sosiale medier, flommer over av artikler om biohacking (overstyring av biologiske prosesser). Talspersoner for biohacking ser for seg kroppen som en kompleks maskin der de individuelle delene kan erstattes, og kjemien som foregår i cellene som bygger opp denne maskinen, kan optimaliseres ved å overstyre biologiske prosesser for å unngå aldring. Lite av det som foreslås er fundert i solid kunnskap om effekt, men i likhet med mange gode historier har flere av ideene et snev av sannhet i seg. I denne kronikken gir vi en oversikt over mekanismene som fører til aldring. Vi vil også diskutere hvordan disse kan være relevante for forståelsen av sykdom og for hvordan vi kan få flest mulig sunne leveår.

• Arranz, Lorena (2025). Uncovering novel treatments for patients of myeloid leukemias. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Uncovering novel treatments for patients of myeloid leukemias. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2025). Exploring the transformation potential of haematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2025). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia (AML) progression. Fulltekst i vitenarkiv
• Fuertes, Alba Soto & Arranz, Lorena (2025). Development of a method to predict patients of myeloid malignancies with best chances of success for blocking inflammation as therapeutic strategy. Fulltekst i vitenarkiv
• Arranz, Lorena & Lawrence, Leah (2025). Which Studies at EHA 2025 May Change Practice? [Internet]. Oncology News Central. Fulltekst i vitenarkiv Vis sammendrag

  The European Hematology Association 2025 Congress kicks off on June 12 in Milan, Italy, and will provide updates “on the most recent breakthroughs in both clinical and translational hematology,” says Lorena Arranz, PhD, a member of the meeting’s Scientific Program Committee.

• Massiah, Nadine Simone; Tanbo, Tom Gunnar; Rajkumar, Hemamaalini; Vera-Rodriguez, Maria & Fedorcsak, Peter Zoltan (2025). OncoFertBot: quality and safety of a conversational AI assistant for retrieving oncofertility guidelines for clinical decision-making. Human Reproduction. ISSN 0268-1161. 40(Supplement 1). doi: https:/scholar.google.no/scholar?oi=bibs&cluster=861185255337094396&btnI=1&hl=no. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Therapeutic targeting of stem cells and their niches in age-related myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Restoring the control over inflammation as therapy against acute myeloid leukemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv
• Li, Yanjiao (2024). Hva kan vi lære av embryo-utvikling i kampen mot kreft? doi: https:/www.oslo-universitetssykehus.no/om-oss/innsikt/hva-kan-vi-lare-av-embryo-utvikling-i-kampen-mot-kreft/. Fulltekst i vitenarkiv
• Cuminetti, Vincent; Konieczny, Joanna; Mera, Aurora Bernal; Oliver, Marc Ferre; Gomez, Manuel José & Vilaplana-Lopera, Nuria [Vis alle 18 forfattere av denne artikkelen] (2024). Succinate receptor 1 signaling regulates hematopoiesis via S100/a8 and S100/a9 in health and malignancy. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Introduction to Bone Marrow Physiology and Pathophysiology - Opportunities for Imaging. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2024). Succinate receptor 1 signaling regulates hematopoiesis via S100/a8 and S100/a9 in health and malignancy. Fulltekst i vitenarkiv
• Cuminetti, Vincent; Konieczny, Joanna; Boet, Emeline; Mera, Aurora Bernal; Oliver, Marc Ferré & Gomez, Manuel José [Vis alle 20 forfattere av denne artikkelen] (2024). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Restoring the control over inflammation as therapy against myeloid malignancies. Fulltekst i vitenarkiv
• Vikedal, Krister; Skarstad, Kirsten; Bjørås, Magnar; Helgesen, Emily & Booth, James Alexander (2026). DNASupercompaction: A Novel Orchestrated Response to Severe DNA Damage in Bacteria. Universitetet i Oslo. ISSN 9788234807695. Fulltekst i vitenarkiv Vis sammendrag

  Bacteria respond to antibacterial drug exposure by activating stress responses. These responses can promote survival and drive resistance development, thereby compromising antibacterial drug effectiveness. Studying bacterial stress responses is therefore essential for guiding measures that help ensure treatments remain effective. The aim of this thesis was to investigate how bacteria rearrange their chromosome when exposed to severe DNA damage caused by antibacterial drugs. Using Escherichia coli exposed to the antibacterial drug ciprofloxacin as a model system, live-cell microscopy revealed an ordered two-step nucleoid rearrangement that culminates in a dense and persistent midcell compaction. This response, termed DNA supercompaction, was also observed after exposure to other DNA-damaging agents and across bacterial species, including clinical isolates, underscoring its broader biological relevance. The genetic landscape of DNA supercompaction was explored through a genome-wide screening combined with machine learning-assisted analysis of compaction phenotypes. Key DNA repair proteins, RecA, RecBCD, and RecN, emerged as essential orchestrators of the response. Additionally, single-cell fluorescence imaging revealed a dynamic interplay between RecA and RecN at nucleoid-associated positions during DNA supercompaction. Overall, this work identifies DNA supercompaction as an important and conserved component of the bacterial DNA damage response and provides a framework for future studies of this newly recognized layer of bacterial stress adaptation, which may prove relevant for preserving antibacterial drug effectiveness.

• Phan, Veronica Q. T.; Olsen, Jorunn Elisabeth; Mageroy, Melissa & Huynh, Bao Ngan (2024). Mechanisms of defence priming in Norway spruce (Picea abies) seeds using methyl jasmonate and chitosan. Norges miljø- og biovitenskapelige universitet (NMBU). Fulltekst i vitenarkiv Vis sammendrag

  Norway spruce (Picea abies (L.) H. Karst.) is a beneficial conifer species in Europe, especially in forestry. The increasing demand of Norway spruce has led to high production of seedlings in growth facilities. Growth conditions in these facilities contribute to fungal outbreaks, and the continuous use of fungicides to combat fungal infections will eventually develop resistance in the fungi. Applying chemical compounds directly to the seeds to prime inducible defences may be a simpler and safer method to protect the seedlings. In this study, seeds were treated with the chemicals methyl jasmonate (MeJA) and chitosan (Chi) to determine if seed priming is possible in Norway spruce. Furthermore, seeds were also treated with JAR, and a combination of JAR and MeJA or Chi, to investigate the hormone signalling pathways involved in MeJA and Chi induced defence responses. To establish the effects of these chemicals, the germination percentage and phenotypes of 4-week-old seedlings were evaluated. Additionally, 4-week-old seedlings were challenged with mechanical wounding and MeJA to determine if the seed treatments had an influence on defence responses. Gene expression levels of seven defence-related genes (CHI4, CHI2, NRPE1, ROS1, JAR1, LAR3, LOX) were quantified at two time points after challenge. In addition, chitinase enzyme activity was measured. The findings of this study indicates that the chemicals MeJA and Chi can possibly penetrate the seed coats of Norway spruce, making seed priming possible. However, this study did not include all defence responses and most genes did not reveal any priming effect, thus it was difficult to determine the signalling pathways involved in defence responses. Overall, the ontogeny of Norway spruce may play a major role in the activation of various defence mechanisms.

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