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Coming dissertations at Uppsala university

  • Identification and Functional Significance of Aberrant Long Non-coding RNAs in Acute Myeloid Leukemia : Biological and Prognostic Implications Author: Anne H. Neddermeyer Link: Publication date: 2022-05-20 14:10

    Acute myeloid leukemia (AML) is the most frequently diagnosed type of acute leukemia in adults. It commonly affects people aged 60 or older, as incidence increases with age, and it is characterized by the accumulation of immature hematopoietic progenitor cells in the bone marrow. Despite recent treatment advances and improvements for certain subtypes, as acute promyelocyte leukemia (APL), AML remains difficult to cure. While many patients reach remission after induction treatment, relapses are common and 5-year overall survival remains dismal. Long non-coding RNAs (lncRNAs) are involved in various regulatory cellular functions and, like coding genes, they are frequently dysregulated in cancer. 

    In this thesis, the aim was to elucidate the functional implications of lncRNAs in the biology and treatment response of AML and normal hematopoiesis in order to improve understanding of AML pathology. In Paper I, whole-transcriptome sequencing identified the novel lncRNA MALNC. Clinical correlation analyses and CRISPR-knockout cell models were used to functionally explore its implications in AML. It was identified that enhanced MALNC expression is specifically associated with the AML-subtypes APL and AML with co-mutant NPM1/IDH2R140. Further, it was shown that MALNC is implicated in key factors of leukemogenesis, like differentiation and proliferation, and that MALNC expression associates with better overall survival in AML patients. Moreover, knockout of the MALNC gene sensitized AML cells to arsenic trioxide (ATO), all-trans retinoic acid (ATRA)-ATO combination and venetoclax treatment. In Paper II, three high-throughput functional CRISPR interference screens were performed to identify lncRNAs implicated in proliferation, differentiation or venetoclax response. Several novel lncRNAs were identified to potentially play a positive or negative role in these processes and furthermore were found to implicate AML prognosis. In Paper III, the lncRNA NEAT1 was studied in respect to its role in normal hematopoiesis and AML using CAGE- and RADICL-sequencing. It could be illustrated that NEAT1 expression positively correlates with cell maturity during normal hematopoiesis, in particular monocytes, and associates with core-binding factor AML inv(16) and t(8;21). Further, RADICL-sequencing identified that lncRNA NEAT1 binds to the genomic loci of key hematopoietic transcription factor RUNX2. In contrast to solid cancers, it was demonstrated, that higher NEAT1 expression correlated with better outcome in AML, independent of known risk factors. 

    In summary, these studies have outlined the scope of functional implications of lncRNAs in normal and dysregulated hematopoiesis and have highlighted their potential roles as biomarkers for prognosis and drug sensitivity. These findings support the efforts to understand how lncRNAs could serve as novel biomarkers for personalized treatment.

  • Reaching for Excellence? : Does training improve motor abilities and cause cascading effects in the visual attention and social perception domain? Author: Linda van den Berg Link: Publication date: 2022-05-20 11:52

    claimed in the last 20 years. Being able to reach for objects provides infants with an interactive interface with their environment. After reach onset, objects can be explored closer to the face and manipulated. Social perception abilities and visual attention have both been found to relate to motor development. We can observe successful reaching and grasping between the ages of 4 and 6 months of age. Research has proposed that these abilities can be observed sooner if infants take part in a reaching training. The sticky mittens training has been put forward as a training that can help infants reach before they would normally start reaching. Moreover, the training has been suggested to increase social perception and visual attention. 

    Therefore, the aim of this thesis is to examine whether this training affects infant abilities in these three domains (motor, social perception, and visual attention) at the age of 3 months and 10 months. In this thesis, three studies are presented. Study I described the sticky mittens field and gave an overview of what we currently know about the training’s effects. Study II examined whether the sticky mittens training affects the emergence of reaching and grasping using the original task from the sticky mittens literature and a new task. Study III examined whether the sticky mittens training affected social perception and visual attention abilities.

    The main results in Study I were that the sticky mittens effects are inconsistent in the motor domain and visual attention domain. However, the effects seemed robust in the social perception domain. In Study II, the main results were that the training was unable to improve reaching and grasping, as indicated by the lack of reaching and grasping in the original and new tasks. In Study III, it was found that the training did not affect social perception and visual attention. In conclusion, the training did not work in the current sample. However, there is not enough evidence to conclude that the training is either effective or ineffective.

  • Drawing Science : Visual Content Formation in Young Students’ Multimodal Science Compositions Author: Elin Westlund Link: Publication date: 2022-05-20 10:34

    This thesis explores visual formation of science content in young students’ multimodal text-image compositions. In doing so, it also contributes a metalanguage for visual meaning-making about science content in the early school years. Using social semiotic theory, the images and image-text relations of 93 multimodal compositions made by eight-year-old students as part of their science education were analysed. The results show that young students’ visual formation of science content in their text-image compositions is diverse and often complex. The thesis introduces seven types of content representation: theory, natural experience, event, art, person, attitude-evoking, and cultural heritage. These are usually combined with some of the other types. An in-depth analysis of these combinations suggests that the representations do not carry the same weight in creating a coherent multimodal science composition – they either function as the main representation or as a modifier. Mapping students’ representations in relation to teaching also indicates the impact teaching has on students’ visual formation of science content. Furthermore, a broadened analysis provided insights into three types of functions that aesthetics have for visual formation of science content. Each of these fulfils a set of values that makes it more or less aligned with the norms of science. The types correspond to a classic science norm, an extended science norm, and an artistic norm, respectively. Finally, the discussion outlines the implications of the results for teaching and learning. The results are discussed in relation to a broadened focus on content in literacy teaching during the early school years, followed by a discussion on how contributed metalanguage and methodology could function as tools for explicit teaching and assessment, and representations as tools for understanding. In conclusion, the thesis provides a flexible addition to the toolbox for students, teachers and researchers interested in how meaning-making about science content during the early school years works in relation to knowledge and norms.