Characterization of oncogenic role of ROR1 and PTK7 in B-ALL

Background and aims: Pseudokinases are members of the protein kinase superfamily that have mutations in their canonical motifs required for proper catalytic activity. Many pseudokinases are involved in human diseases, therefore it is important to understand their signaling mechanisms and regulation. Among pseudokinases family, receptor tyrosine kinase-like orphan receptors (RORs) and protein tyrosine kinase 7 (PTK7) are Wnt-binding receptors from non-canonical Wnt signaling pathway. These proteins are expressed in several cancers, but their functional role needs more investigation. In this thesis, we investigated the oncogenic role of ROR1 and PTK7 in B-cell acute lymphoblastic leukemia (B-ALL). Methods: In this study, we used B-ALL cells with t(1;19) translocation. We investigated the expression of ROR1 and PTK7 as well as intracellular Wnt signaling pathway using Western Blotting and FACS analysis. We also examined the interaction of Wnt5a ligand with ROR1 and PTK7 using immunoprecipitations. To examine molecular pathway downstream from ROR1 and the relevance of ROR1 and PTK7 in cell survival, we targeted ROR1 with monoclonal antibody and both ROR1 and PTK7 with RNA interference system. Results: Our results demonstrate that both ROR1 an PTK7 are expressed on B-ALL cells with t(1;19) translocation but only ROR1 is important for B-ALL cell survival. We showed that ROR1 interacts with Wnt5a indicating that ROR1 is a mediator of non-canonical Wnt signaling. Also, we demonstrated downregulation of RhoA, STAT3 and NF-?B after ROR1 targeting. Conclusion: ROR1 has an important role maintaining B-ALL t(1;19) cell viability in non-canonical Wnt signaling pathway. ROR1 targeting reduces cell survival indicating it as a possible candidate for targeted therapy

Manually curated and harmonised transcriptomics datasets of psoriasis and atopic dermatitis patients

We present manually curated transcriptomics data of psoriasis and atopic dermatitis patients retrieved from the NCBI Gene Expression Omnibus and EBI ArrayExpress repositories. We collected 39 transcriptomics datasets, deriving from DNA microarrays and RNA-Sequencing technologies, for a total of 1677 samples. We provide quality-checked, homogenised and preprocessed gene expression matrices and their corresponding metadata tables along with the estimated surrogate variables. These data represent a ready-made valuable source of knowledge for translational researchers in the dermatology field.Peer reviewe

Liikenne- ja viestintäministeriön vastuullisuusraportti 2021 : Kuvaus ministeriön toimista vuonna 2021 kestävän kehityksen Agenda 2030 -tavoitteiden saavuttamiseksi

Liikenne- ja viestintäministeriö on laatinut ensimmäistä kertaa vastuullisuusraportin, johon on koottu tietoa siitä, millä toimenpiteillä liikenne- ja viestintäministeriö on edistänyt YK:n kestävän kehityksen Agenda2030-tavoitteiden saavuttamista vuonna 2021. Liikenne- ja viestintäministeriön rooli on erityisesti edistää sosiaalisesti, taloudellisesti ja ympäristön kannalta kestävää liikennejärjestelmää sekä toimivaa ja kattavaa digitaalista infrastruktuuria. Ilmastonmuutoksen hidastamisessa liikenteen, etenkin tieliikenteen päästöjen vähentäminen, on keskeisessä roolissa. Tärkeitä ovat myös esteettömyyttä ja liikenneturvallisuutta edistävät toimet. Valtiokonttori suosittaa kaikkia valtion virastoja laatimaan toiminnastaan vastuullisuusraportin vuosittain. YK:n kestävän kehityksen Agenda2030-tavoitteet ovat Valtiokonttorin ohjeistaman vastuullisuusraportoinnin perusta

Characterization of oncogenic role of ROR1 and PTK7 in B-ALL

Background and aims: Pseudokinases are members of the protein kinase superfamily that have mutations in their canonical motifs required for proper catalytic activity. Many pseudokinases are involved in human diseases, therefore it is important to understand their signaling mechanisms and regulation. Among pseudokinases family, receptor tyrosine kinase-like orphan receptors (RORs) and protein tyrosine kinase 7 (PTK7) are Wnt-binding receptors from non-canonical Wnt signaling pathway. These proteins are expressed in several cancers, but their functional role needs more investigation. In this thesis, we investigated the oncogenic role of ROR1 and PTK7 in B-cell acute lymphoblastic leukemia (B-ALL). Methods: In this study, we used B-ALL cells with t(1;19) translocation. We investigated the expression of ROR1 and PTK7 as well as intracellular Wnt signaling pathway using Western Blotting and FACS analysis. We also examined the interaction of Wnt5a ligand with ROR1 and PTK7 using immunoprecipitations. To examine molecular pathway downstream from ROR1 and the relevance of ROR1 and PTK7 in cell survival, we targeted ROR1 with monoclonal antibody and both ROR1 and PTK7 with RNA interference system. Results: Our results demonstrate that both ROR1 an PTK7 are expressed on B-ALL cells with t(1;19) translocation but only ROR1 is important for B-ALL cell survival. We showed that ROR1 interacts with Wnt5a indicating that ROR1 is a mediator of non-canonical Wnt signaling. Also, we demonstrated downregulation of RhoA, STAT3 and NF-?B after ROR1 targeting. Conclusion: ROR1 has an important role maintaining B-ALL t(1;19) cell viability in non-canonical Wnt signaling pathway. ROR1 targeting reduces cell survival indicating it as a possible candidate for targeted therapy

Supplemental Material - A Human Cell-based Assay to Assess the Induction of Vasculature Formation for Non-genotoxic Carcinogenicity Testing Purposes: A Pilot Study

Supplemental Material for A Human Cell-based Assay to Assess the Induction of Vasculature Formation for Non-genotoxic Carcinogenicity Testing Purposes: A Pilot Study by Veera Hautanen, Tarja Toimela, Martin Paparella, and Tuula Heinonen in Alternatives to Laboratory Animals</p

Esperanto : a GLP-field sEmi-SuPERvised toxicogenomics metadAta curatioN TOol

Biological data repositories are an invaluable source of publicly available research evidence. Unfortunately, the lack of convergence of the scientific community on a common metadata annotation strategy has resulted in large amounts of data with low FAIRness (Findable, Accessible, Interoperable and Reusable). The possibility of generating high-quality insights from their integration relies on data curation, which is typically an error-prone process while also being expensive in terms of time and human labour. Here, we present ESPERANTO, an innovative framework that enables a standardized semi-supervised harmonization and integration of toxicogenomics metadata and increases their FAIRness in a Good Laboratory Practice-compliant fashion. The harmonization across metadata is guaranteed with the definition of an ad hoc vocabulary. The tool interface is designed to support the user in metadata harmonization in a user-friendly manner, regardless of the background and the type of expertise.Availability and implementationESPERANTO and its user manual are freely available for academic purposes at . The input and the results showcased in are available at the same link.Peer reviewe