DSpace 9

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DSpace is the world leading open source repository platform that enables organisations to:

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Now showing 1 - 9 of 9

Recent Submissions

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    Effects of alcohol on the transcriptome, methylome, and metabolome of in vitro gastrulating human embryonic cells
    (Company of Biologists Ltd, 2025-05-22) Wallén, Essi; Rämö, Karita Katariina; Vehviläinen, Pekka Juhani Jussi; Sokka, Juho Joonas; Lehtonen, Marko; Otonkoski, Timo; Trokovic, Ras; Auvinen, Pauliina S; Kärkkäinen, Olli; Kaminen-Ahola, Nina; Medicum; Department of Medical and Clinical Genetics; Environmental Epigenetics Laboratory; Medicum; STEMM - Stem Cells and Metabolism Research Program; Helsinki One Health (HOH); Centre of Excellence in Stem Cell Metabolism; HUS Children and Adolescents; Clinicum; Research Programs Unit; Timo Pyry Juhani Otonkoski / Principal Investigator; Children's Hospital
    Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neurodevelopmental disorders and birth defects. To explore the effects of PAE on gastrulation, we used an in vitro model with subchronic moderate (20 mM) and severe (70 mM) ethanol exposures during the differentiation of human embryonic stem cells into germ layer cells. We analysed genome-wide gene expression (mRNA sequencing), DNA methylation (EPIC Illumina microarrays), and metabolome (non-targeted LC-MS) of the endodermal, mesodermal, and ectodermal cells. The largest number of ethanol-induced alterations were observed in endodermal cells, whereas the most prominent changes were in ectodermal cells. Methionine metabolism and genes of the major signaling pathways involved in gastrulation and body patterning were affected by ethanol in all germ layers. Many of the altered genes, including BMP4, FGF8, SIX3, and LHX2, have previously been associated with PAE and phenotypes of FASD, like defects in heart and corpus callosum development as well as holoprosencephaly. Our findings support the early origin of alcohol-induced developmental disorders and strengthen the role of methionine cycle in the etiology of FASD.
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    Acquired and genetic drivers of C3 and C5 convertase dysregulation in C3 glomerulopathy and immunoglobulin-associated MPGN
    (Oxford University Press, 2024-12) Roquigny, Julia; Meuleman, Marie-Sophie; El Sissy, Carine; Martins, Paula Vieira; Meri, Seppo; Duval, Anna; Le Quintrec, Moglie; Fakhouri, Fadi; Chauvet, Sophie; Fremeaux-Bacchi, Veronique; TRIMM - Translational Immunology Research Program; University of Helsinki; Department of Bacteriology and Immunology; HUSLAB; Seppo Meri / Principal Investigator; Research Programs Unit; HUS Chemistry and Microbiology
    Dysregulation of the alternative pathway of complement plays a central role in the pathophysiology of C3 glomerulopathy (C3G). Various autoimmune and genetic factors targeting the alternative pathway have been associated with both C3G and primary immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN), suggesting shared pathophysiological mechanisms. This review highlights the wide range of disease drivers identified that mainly target components or protein complexes of the alternative pathway, both in C3G and Ig-MPGN. Nephritic factors, which constitute a heterogeneous group of autoantibodies targeting the C3 or the C5 convertase, are the most common abnormalities. Monoclonal gammopathies are frequent in aging adults. They may promote complement activation and have in some cases also been found to target alternative pathway regulatory proteins. Additionally, some patients with C3G and Ig-MPGN carry rare variants in genes encoding complement activating or regulating proteins of the alternative pathway. This review provides an informative overview of pathogenetic mechanisms associated with each abnormality, acting at different steps in the complement cascade. The diversity of targets involved in the C3G pathophysiology suggests the potential benefit of therapeutical approaches tailored to the underlying disease drivers, with a pivotal impact upstream or at the level of the C3 or C5 convertase activity.
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    Does IPSS-R downstaging before transplantation improve the prognosis of patients with myelodysplastic neoplasms?
    (Elsevier B.V., 2024-07-25) Scheid, Christof; Eikema, Diderik-Jan; van Gelder, Michel; Salmenniemi, Urpu; Maertens, Johan; Passweg, Jakob; Blaise, Didier; Byrne, Jennifer L.; Kröger, Nicolaus; Sockel, Katja; Chevallier, Patrice; Bourhis, Jean Henri; Cornelissen, Jan J.; Sengeloev, Henrik; Finke, Jürgen; Snowden, John A.; Gedde-Dahl, Tobias; Cornillon, Jérôme; Schanz, Urs; Patel, Amit; Koster, Linda; de Wreede, Liesbeth C.; Hayden, Patrick; Raj, Kavita; Drozd-Sokolowska, Joanna; Gurnari, Carmelo; Onida, Francesco; McLornan, Donal P.; Robin, Marie; Yakoub-Agha, Ibrahim; Clinicum; HUS Comprehensive Cancer Center; Department of Oncology
    In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients.
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    Profiles of Approaches to Writing and Their Links to Self-Efficacy and LLM Acceptance in L2 Academic Writing
    (2025-07-20) Sun, Fei; Mendoza, Laura; Wang, Junju; Li, Hongbin
    Approaches to writing play an important role in both the writing processes and outcomes. However, little is known about whether L2 writers adopt different combinations of approaches in academic writing contexts and what factors predict such combinations. Hence, this study aimed to identify different profiles of approaches to writing in an L2 academic context and examine how they are predicted by writing self-efficacy and large language model (LLM) acceptance. To this end, a total of 578 Chinese graduate students were recruited to participate in the study. Latent profile analysis revealed three distinct writing profiles: unorganized (Profile 1), dissonant (Profile 2), and deep and organized (Profile 3), with the majority of students categorized under the dissonant profile. Additionally, multinomial logistic regression analysis revealed that writing self-efficacy positively predicted profile membership, with the strongest effect observed for Profile 3, followed by Profile 2 and then Profile 1. LLM acceptance also positively predicted profile membership, with the strongest effect for Profile 2, followed by Profile 3 and then Profile 1.
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    Highly selective uranium separation using sulfonic acid‑functionalized hierarchically porous zirconium phosphate: Modelling and mechanism study
    (Elsevier, 2025) Zhang, Shouxin; Li, Xiaodong; Huang, Xinhui; Szlachta, Małgorzata; Bao, Hongli; Xu, Junhua; Geologian tutkimuskeskus; Geological Survey of Finland
    The growing challenges of nuclear pollution necessitate the development of advanced sorption materials with high efficiency and improved selectivity. In this work, a hierarchical porous zirconium phosphate sorbent (H-ZrP) was synthesized via a facile self-assembly strategy, and its sulfonic acid-functionalized derivative (H-ZrP-SO3H) was developed for selective U(VI) removal. Comprehensive characterization demonstrates that H-ZrP possesses a unique hierarchical pore architecture, high specific surface area, and excellent thermal stability. Batch experiments reveal that both materials exhibit exceptional U(VI) sorption capacities: 372.4 mg g−1 for H-ZrP and 290.5 mg g−1 for H-ZrP-SO3H. Kinetic and isotherm analyses confirm chemisorption-dominated monolayer sorption, well-described by pseudo-second-order (R2 > 0.99) and Langmuir models (R2 > 0.98). H-ZrP-SO3H achieves higher selectivity in V/U systems despite reduced porosity due to optimized surface charge interactions. H-ZrP and H-ZrP-SO3H demonstrate outstanding reusability, retaining > 99 % removal efficiency after five sorption–desorption cycles with preserved structural integrity. Surface complexation modelling reveals that the sorption process is dominated by a multi-stage sorption mechanism: electrostatic attraction and surface complexation via oxygenated groups. In summary, this work presents highly efficient functionalized phosphate-based sorbents to regulate interfacial charge dynamics for enhanced U(VI) sorption.