Relative affinity constants by electrospray ionization and Fourier transform ion cyclotron resonance mass spectrometry: calmodulin binding to peptide analogs of myosin light chain kinase

Synthetic RS20 peptide and a set of its point-mutated peptide analogs have been used to analyze the interactions between calmodulin (CaM) and the CaM-binding sequence of smooth-muscle myosin light chain kinase both in the presence and the absence of Ca2+. Particular peptides, which were expected to have different binding strengths, were chosen to address the effects of electrostatic and bulky mutations on the binding affinity of the RS20 sequence. Relative affinity constants for protein/ligand interactions have been determined using electrospray ionization and Fourier transform ion cyclotron resonance mass spectrometry. The results evidence the importance of electrostatic forces in interactions between CaM and targets, particularly in the presence of Ca2+, and the role of hydrophobic forces in contributing additional stability to the complexes both in the presence and the absence of Ca2+

Teacher competencies in game-based pedagogy

This study examines what kind of competencies teachers need in using game-based pedagogy (GBP). In our conceptual framework, GBP entails four approaches: using educational games or entertainment games, learning by making games, and using gamification in learning. Our data, consisting of teachers’ documentation, thematic interviews and questionnaires, were analysed using qualitative content analysis. Four main competence areas were identified: pedagogical, technological, collaborative and creative. The results are applicable for developing teacher education and in-service training, as teacher competencies in game-based learning will be more integral to teachers’ professional knowledge and skill repertoires.peerReviewe

The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1

Originally identified in Drosophila melanogaster, the Warts(Wts)/Lats protein kinase has been proposed to function with two other Drosophila proteins, Hippo (Hpo) and Salvador (Sav), in the regulation of cell cycle exit and apoptosis. In mammals, two candidate Warts/Lats homologs, termed Lats1 and Lats2, have been described, and the targeted disruption of LATS1 in mice increases tumor formation. Little, however, is known about the function and regulation of human Lats kinases. Here we report that human Mst2, a STE20-family member and purported Hpo ortholog, phosphorylates and activates both Lats1 and Lats2. Deletion analysis revealed that regulation of Lats1 occurs through the C-terminal, catalytic domain. Within this domain, two regulatory phosphorylation sites were identified by mass spectrometry. These sites, S909 in the activation loop and T1079 within a hydrophobic motif, have been highly conserved during evolution. Moreover, a direct interaction was observed between Mst2 and hWW45, a putative ortholog of Drosophila Sav. These results indicate that Mst2-like kinases regulate Lats kinase activities in an evolutionarily conserved regulatory pathway. Although the function of this pathway remains poorly understood in mammals, it is intriguing that, in Drosophila, it has been linked to development and tissue homeostasis

LUKILOKI : virtaa ja välineitä luku- ja kirjoitustaidon ohjaamiseen

“Mukavaa, kun tässä koulutuksessa tutkimus kohtaa arjen”, tiivisti LUKILOKI-koulutuksen osallistuja kokemuksiaan. Valtakunnallisen, 1600 opettajaa tavoittavan LUKILOKI-täydennyskoulutuksen tavoitteena on tarjota opetushenkilöstölle luku- ja kirjoitustaidon ohjaamiseen ja tukemiseen liittyvää tutkimustietoa ja käytännön työkaluja. Koulutuksen keskiössä ovat muun muassa lukumotivaatio, arviointi ja oppimisen tukeminen luki- ja oppimisvaikeuksien sekä S2-opetuksen ja monikielisyyden näkökulmista. Tässä artikkelissa kuvataan hankkeen tavoitteita ja tuotoksia, joita opettajat voivat hyödyntää työnsä tukena.nonPeerReviewe

An interlaboratory comparison on whole water samples

The European Water Framework Directive 2000/60/EC requires monitoring of organic priority pollutants in so called “whole water” samples, i.e. in aqueous non-filtered samples that contain natural colloidal and suspended particulate matter. Colloids and suspended particles in the liquid phase constitute a challenge for sample homogeneity and stability. Within the joint research project ENV08 “Traceable measurements for monitoring critical pollutants under the European Water Framework Directive 2000/60/EC” whole water test materials were developed by spiking defined amounts of aqueous slurries of ultra-finely milled contaminated soil or sediment and aqueous solutions of humic acid into a natural mineral water matrix. This paper presents the results of an European-wide interlaboratory comparison (ILC) using this type of test materials. Target analytes were tributyl tin, polybrominated diphenyl ethers and polycyclic aromatic hydrocarbons in the ng/L concentration range. Results of the ILC indicate that the produced materials are sufficiently homogeneous and stable to serve as samples for e.g. proficiency testing or method validation. To our knowledge, this is the first time that ready to use water materials with a defined amount of suspended particulate and colloidal matter have been applied as test samples in an interlaboratory exercise. These samples meet the requirements of the European Water Framework Directive. Previous proficiency testing schemes mainly employed filtered water samples fortified with a spike of the target analyte in a water-miscible organic solvent.JRC.D.2-Standards for Innovation and sustainable Developmen

Efficacy of conventional-dose cytarabine, idarubicin and thioguanine versus intermediate-dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia : Long-term results of the prospective randomized nationwide AML-2003 study by the Finnish Leukemia Group

Objectives: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy. Methods: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively. Results: A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p <.001). Conclusions: Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future.acceptedVersionPeer reviewe