Browsing by study line "Cross-disciplinary translational medicine"
Now showing items 41-43 of 43
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(2021)Every childbirth is a unique experience for a mother and the whole family. While there is growing evidence that childbirth has long-term implications for a mother’s life, and that a personal childbirth experience is in a major role in determining those implications, personal birth experiences have not yet come to the centre of labour care in Finland. In this qualitative study I investigated the constitutive elements of personal childbirth experiences. The material consisted of 29 birth stories written by 20 mothers, collected as a part of a larger research project Battles over Birth – Finnish Birth Culture in Transition (2020-2023), funded by the Kone Foundation. I divided the stories into positive and negative experiences based on how mothers described the events and their implications. I analysed the role of pain management in all experiences, after which other elements were identified from each story and compared within category and finally between categories. In addition, I analysed the long-term implications of positive and negative experiences for mothers. Systematic content analysis suggested three elements as crucial in determining whether the experience was valued as positive or negative, and these were: 1) pain and pain management, 2) interaction with professionals, and 3) sense of control and self-determination. The birth experience had implications on the mother-infant bond, mental health, trust toward health care professionals, number of subsequent children, general well-being, and confidence in motherhood. The birth experience thus constitutes of several aspects and can have significant long-term implications. By considering mothers’ wishes and treating them respectfully, not only is their constitutional right for self-determination respected, but a safe and comfortable environment can be created for labour. The findings of this study can contribute to developing maternity and childbirth care toward patient-centred care, where personal birth experiences have more value and positive birth experiences can be ensured.
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(2019)Lipid droplets (LDs) are ubiquitous intracellular storage organelles, consisting of a core of energy rich neutral lipids surrounded by a phospholipid monolayer. Research in the past decade has expanded the view on LDs from simple, passive cytosolic inclusions to dynamic organelles which play an important role in many cellular processes. Furthermore, there is mounting evidence for links between LD biology and human pathologies, such as metabolic disorders, non-alcoholic fatty liver disease and cardiovascular diseases. Thus, understanding the basic biology of LD formation is crucial. LD biogenesis is thought to occur in the microdomains of endoplasmic reticulum (ER), due to the accumulation of neutral lipids between the two leaflets of the ER bilayer before budding into the cytosol. Many proteins are involved in this early formation, but no single indispensable protein has been discovered. After assembly, these early LDs grow through lipid deposition from the ER, and with lipid synthesis on the droplet monolayer. During LD growth, LDs are thought to retain connection to the ER. A protein important for LD biogenesis is seipin. This oligomeric ER protein has been found to localize at contact sites between the ER and LDs. Mutations in seipin give rise to three distinct diseases in humans; BSCL2, seipinopathy and Celia’s encephalopathy. The role of seipin in the formation of LDs and the pathogenesis of these diseases is still unknown. Work from numerous model systems has shown seipin to be important for LD biogenesis and adipocyte differentiation. LD formation is a complex process which is still poorly understood, and seipin likely collaborates with other proteins during LD assembly. In this thesis, APEX2-mediated proteome mapping combined with LC-MS/MS, is set up to identify proteins involved in LD biogenesis. In this technology, an engineered ascorbate peroxidase, APEX2, is genetically inserted to the intracellular region of interest where it rapidly biotinylates nearby endogenous proteins upon exposure to biotin-phenol and hydrogen peroxide. Biotinylated proteins can then be enriched by using streptavidin beads and identified with a mass spectrometry. The aim using this technology is to unravel new interaction partners of seipin and proteins important for LD formation, which is a crucial step for understanding LD formation and diseases related to it.
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(2023)Antibiotic-resistant bacteria present a severe threat to global health. The future treatment of common bacterial infections relies on the identification of novel antibiotics and targets in the present. One area of antimicrobial research is the study of bacteriophage (Petrovic Fabijan et al.) mechanisms and the identification of phage-derived antimicrobials. Sequenced phage genomes are largely (>70%) annotated as “hypothetical proteins of unknown function” (HPUFs) and investigation into HPUFs with a toxic effect on host bacteria (toxHPUFs) aims to reveal new antibacterial targets and antimicrobials. Next-generation sequencing and plating-based toxicity screening of Staphylococcus phage Stab21 HPUFs identified nine HPUFs that incurred toxicity to Escherichia coli. In this study, the tightly controlled tetracycline-inducible plasmid pRAB11N was used as a shuttle vector and verified the toxicity of five out of nine HPUFs to E. coli and revealed that no HPUFs caused toxicity to the Stab21 natural target and clinically relevant Staphylococcus aureus. These results suggest that screening for toxHPUFs should be carried out in closely related bacterial species or the phages’ natural host. The five toxHPUFs of E. coli were further characterised by protein function and structural predictions. Only one toxHPUF, g024, returned a reliable model with homology to Bacillus phage SPO1 homing endonuclease I-HmuI, yet the role of this DNase in bacterial host toxicity is still unknown. To determine the bacterial targets of the toxHPUFs, spontaneous toxin-insensitive mutants of the five toxHPUFs were investigated. For three toxHPUFs, the toxin insensitivity was ascribed to the elimination of the toxin-encoding gene. However, toxin-insensitive g172 and g187 sequences revealed mutations in the tetR gene of pRAB11N that led to the inability of tetracycline binding and thus no induction of gene expression and did not aid in identifying the bacterial targets of these toxHPUFs. This study highlights the experimental complexities of phage-derived antimicrobial research. It also maintains the value of this research strategy, with the verification of HPUFs with a toxic effect on E. coli and accompanied future studies of bacterial target determination having the potential to uncover novel antimicrobial mechanisms that can be exploited for therapeutic application.
Now showing items 41-43 of 43