C-reactive protein (CRP), a plasma protein of the innate immune system, is produced by hepatocytes. A critical regulatory region (-42 to -57) on the CRP promoter contains binding site for the IL-6-activated transcription factor C/EBPβ. The IL-1β-activated transcription factor NF-κB binds to a κB site located nearby (-63 to -74). The κB site overlaps an octamer motif (-59 to -66) which is the binding site for the constitutively active transcription factor Oct-1. Oct-1 is known to function both as a transcriptional repressor and as an activator depending upon the promoter context. Also, Oct-1 can regulate gene expression either by binding directly to the promoter or by interacting with other transcription factors bound to the promoter. The aim of this study was to investigate the functions of Oct-1 in regulating CRP expression. In luciferase transactivation assays, overexpressed Oct-1 inhibited (IL-6 + IL-1β)-induced CRP expression in Hep3B cells. Deletion of the Oct-1 site from the promoter drastically reduced the cytokine response because the κB site was altered as a consequence of deleting the Oct-1 site. Surprisingly, overexpressed Oct-1 inhibited the residual (IL-6 + IL-1β)-induced CRP expression through the promoter lacking the Oct-1 site. Similarly, deletion of the Oct-1 site reduced the induction of CRP expression in response to overexpressed C/EBPβ, and overexpressed Oct-1 inhibited C/EBPβ-induced CRP expression through the promoter lacking the Oct-1 site. We conclude that Oct-1 acts as a transcriptional repressor of CRP expression and it does so by occupying its cognate site on the promoter and also via other transcription factors by an as yet undefined mechanism.

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The interaction between fluid dynamics and biofilm growth plays a key role in both medical and industrial applications. Biofilms, or bacteria that are embedded in a protective matrix of extracellular polymeric substances, settle on interfaces such as on implanted devices or ship hulls. These biofilms canthen cause infectious diseases or significantly increase drag. In this thesis, we investigate the influence of flow, specifically shear stress, on the development of biofilm. The first paper presents a new facility to investigate biofilm growth in laminar flow cells over extended periods of up to several weeks. Optical coherence tomography is used to obtain three-dimensional scans of the biofilm structure at regular intervals. From these time series, we derive a simple model that relates the growth of an individual microcolony to the growth of the full biofilm depending on the wall shear stress. Additionally, we show that biofilm streamers, thin, flexible filaments that extend into the bulk flow, can form on sharp biofilm structures in laminar flow, even if the substratum is a flat surface. The second contribution is a report detailing preliminary studies on biofilm experiments. We investigate the formation of biofilm in the shear layer behinda backward-facing step. The results indicate a maximum shear stress, beyond which biofilm growth is inhibited. We also provide guidelines for the design of experimental setups for the investigation of the influence of fluid dynamics on biofilm and vice-versa. / Samspelet mellan fluiddynamik och biofilmtillväxt spelar en nyckelroll i både medicinska och industriella tillämpningar. Biofilmer, eller bakterier som är inbäddade i en skyddande matris av extracellulära polymera substanser, sätter sig på ytor som på implanterade enheter eller fartygsskrov. Dessa biofilmer kan sedan orsaka infektionssjukdomar eller avsevärt öka vattenmotståndet. I den här avhandlingen undersöker vi hur flöde, speciellt skjuvspänning, påverkar utvecklingen av biofilm. I den första artikeln presenteras en ny uppställning för att undersöka biofilmstillväxt i flödesceller med laminärt flöde under längre perioder på upp till flera veckor. Optisk koherenstomografi används för att få tredimensionella skanningar av biofilmstrukturen vid regelbundna intervall. Från dessa tidsserier härleder vi en enkel modell som relaterar tillväxten av en enskild mikrokoloni till tillväxten av hela biofilmen beroende på väggskjuvspänning. Dessutom visar vi att biofilm filament som sträcker sig in i bulkflödet, kan bildas på skarpa biofilmstrukturer i laminärt flöde, även om substratum är en plan yta.  Det andra bidraget är en rapport som beskriver preliminära studier av biofilmsexperiment. Vi undersöker bildandet av biofilm i skjuvskiktet bakom ett bakåtvänt steg. Resultaten indikerar en maximal skjuvspänning, bortom vilken biofilmstillväxt hämmas. / <p>QC 240314</p>

Glaucoma is a leading cause of irreversible vision loss globally, and demands early and accurate diagnosis. OCT has become a key investigative technique in glaucoma, and, although it provides invaluable clinical support, detection of early glaucoma remains imperfect. Recent OCT developments enabled direct assessment of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images. The technique has considerable potential in the assessment of glaucoma, yet it has limited clinical usability due to an incomplete understanding of RNFB features in healthy and glaucoma eyes and the lack of accepted methods to identify reflectance defects. This thesis aimed to better understand characteristics of RNFB reflectance in en face OCT imaging and to develop objective methods to extract defects in this domain. Structural and functional measures of glaucoma changes were collected in eyes with established glaucoma and age-similar controls. Results showed that the healthy configuration of RNFB varies across the retina and between different eyes. We developed a method for automated and objective examination of reflectivity changes in en face images. This method considers individual anatomy and varying RNFB configuration, and found more abnormalities than previous approaches. Measures of en face reflectance and conventional retinal nerve fibre layer thickness were strongly related. The agreement between changes of reflectance and visual function was moderate-to-good, and both testing domains presented concordant abnormalities in all tested eyes. Following further minimisation of artefacts in en face images, direct use of reflectance analysis or its combination with perimetry appear viable and with significant potential for clinical examination of glaucoma.

Caries, the world’s most common chronic disease, remains a major cause of invasive restorative dental treatment. To take advantage of the diagnostic potential of optical coherence tomography (OCT) in contemporary dental prevention and treatment, an intraorally applicable spectral-domain OCT probe has been developed based on an OCT hand-held scanner equipped with a rigid 90°-optics endoscope. The probe was verified in vitro. In vivo, all tooth surfaces could be imaged with the OCT probe, except the vestibular surfaces of third molars and the proximal surface sections of molars within a 'blind spot' at a distance greater than 2.5 mm from the tooth surface. Proximal surfaces of 64 posterior teeth of four volunteers were assessed by intraoral OCT, visual-tactile inspection, bitewing radiography and fiber-optic transillumination. The agreement in detecting healthy and carious surfaces varied greatly between OCT and established methods (18.2–94.7%), whereby the established methods could always be supplemented by OCT. Direct and indirect composite and ceramic restorations with inherent imperfections and failures of the tooth-restoration bond were imaged and qualitatively evaluated. The intraoral OCT probe proved to be a powerful technological approach for the non-invasive imaging of healthy and carious hard tooth tissues and gingiva as well as tooth-colored restorations.

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