Yngre elevers lärande om naturen En studie av kommunikation om modeller i institutionella kontexter

Abstract The aim of the study is to draw attention to and examine how young students (approximately 5-13 years) are involved in communication about nature, what approaches to nature are mediated in the social practices of preschool, school, and a science center, and how functional these approaches may be as providing learners with tools for making sense in other situations in everyday life and society. Empirical investigations were carried out by observations, tape recordings and video recordings of interaction in different educational contexts and presented in three studies. The first study is about a group of preschool children (5 years old) and their teacher visiting an exhibition about the water flow at a science center and the teacher communicating with the children about their visit during circle time at the preschool. The second study is about conversations about the water cycle between teachers and young students (8-10 years old) at a primary school, with a prop in the form of a photograph taken in a real rainforest. The third study is about students (12-13 years old) working in pairs in a computer-simulated micro world of ecological processes on an African savanna. Taking a sociocultural perspective, the results indicate that in all the studied contexts, the conversations between the students and teachers were characterized by being indistinct, i.e. not being conducted within a distinct discourse. The students had difficulties following the teachers’ communication strategies. It seemed to be important for the teachers that the students themselves understood what the conversation was about and to arrive at the right answer. Students’ possibility to express their knowledge is closely dependent on the adults’ strategies. The most successful strategy for students is to follow the teacher’s way of speaking. This leads to the fact that some students succeed to talk in such a way that is expected by the teacher in the conversation. When the teacher is absent the students make sense by referring to their previous experience. Without support by the teacher the students thus thematize nature on their own terms. In the investigated activities the models are handled as if being self-illustrative. Models, as such, and how they are related to what they refer to was never explained by the teachers in the studied activities

AML with complex karyotype: extreme genomic complexity revealed by combined long-read sequencing and Hi-C technology

Acute myeloid leukemia with complex karyotype (CK-AML) is associated with poor prognosis, which is only in part explained by underlying TP53 mutations. Especially in the presence of complex chromosomal rearrangements, such as chromothripsis, the outcome of CK-AML is dismal. However, this degree of complexity of genomic rearrangements contributes to the leukemogenic phenotype and treatment resistance of CK-AML remains largely unknown. Applying an integrative workflow for the detection of structural variants (SVs) based on Oxford Nanopore (ONT) genomic DNA long-read sequencing (gDNA-LRS) and high-throughput chromosome confirmation capture (Hi-C) in a well-defined cohort of CK-AML identified regions with an extreme density of SVs. These rearrangements consisted to a large degree of focal amplifications enriched in the proximity of mammalian-wide interspersed repeat (MIR) elements, which often result in oncogenic fusion transcripts, such as USP7::MVD, or the deregulation of oncogenic driver genes as confirmed by RNA-seq and ONT direct cDNA sequencing. We termed this novel phenomenon chromocataclysm. Thus, our integrative SV detection workflow combing gDNA-LRS and Hi-C enables to unravel complex genomic rearrangements at a very high resolution in regions hard to analyze by conventional sequencing technology, thereby providing an important tool to identify novel important drivers underlying cancer with complex karyotypic changes

Genomic heterogeneity in core-binding factor acute myeloid leukemia and its clinical implication

Core-binding factor (CBF) acute myeloid leukemia (AML) encompasses AML with inv(16)(p13.1q22) and AML with t(8;21)(q22;q22.1). Despite sharing a common pathogenic mechanism involving rearrangements of the CBF transcriptional complex, there is growing evidence for considerable genotypic heterogeneity. We comprehensively characterized the mutational landscape of 350 adult CBF-AML [inv(16): n = 160, t(8;21): n = 190] performing targeted sequencing of 230 myeloid cancer-associated genes. Apart from common mutations in signaling genes, mainly NRAS, KIT, and FLT3, both CBF-AML entities demonstrated a remarkably diverse pattern with respect to the underlying cooperating molecular events, in particular in genes encoding for epigenetic modifiers and the cohesin complex. In addition, recurrent mutations in novel collaborating candidate genes such as SRCAP (5% overall) and DNM2 (6% of t(8;21) AML) were identified. Moreover, aberrations altering transcription and differentiation occurred at earlier leukemic stages and preceded mutations impairing proliferation. Lasso-penalized models revealed an inferior prognosis for t(8;21) AML, trisomy 8, as well as FLT3 and KIT exon 17 mutations, whereas NRAS and WT1 mutations conferred superior prognosis. Interestingly, clonal heterogeneity was associated with a favorable prognosis. When entering mutations by functional groups in the model, mutations in genes of the methylation group (ie, DNMT3A, TET2) had a strong negative prognostic impact