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  • 1. Alrifaiy, Ahmed
    et al.
    Borg, Johan
    Lindahl, Olof A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Computer Science, Electrical and Space Engineering, Luleå University of Technology; CMTF, Centre for Biomedical Engineering and Physics, Luleå and Umeå, Sweden; Department of Engineering Sciences and Mathematics, Luleå University of Technology.
    Ramser, Kerstin
    A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy-first investigations of single biological cells2015In: Biomedical engineering online, ISSN 1475-925X, E-ISSN 1475-925X, Vol. 14, article id 36Article in journal (Refereed)
    Abstract [en]

    The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O-2 to an anoxic value of 0.0-0.5% O-2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 +/- 1 s and a fully developed deoxygenated spectrum was observed after 298 +/- 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 +/- 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 +/- 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 +/- 0.412 M Omega and 889.7 +/- 1.74 M Omega respectively.

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  • 2.
    Anderson, Fredrick
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    β3-adrenergic antagonism alleviates weight loss associated with cancer cachexia2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cancer induced cachexia (CIC) is a devastating wasting disorder affecting people with tumor diseases and is deemed responsible for approximately 20% of all cancer-related deaths. This syndrome is associated with atrophy of adipose tissue and skeletal muscle. No established treatment is available for CIC and the underlying mechanisms are unveiled. However, one proposed culprit is brown adipose tissue (BAT) and browning of white adipose tissue (WAT), which produces heat via activation uncoupling protein 1 (UCP1). The result is increased energy wasting. Β3-adrenergic receptor (ADRB3) signaling activates BAT and we hypothesized that treatment with a specific ADRB3 antagonist would mitigate energy wasting in CIC. Balb/ca nude mice implanted with the LuCAP32 human xenograft tumor was used as a model system for CIC. The mice were treated with the selective ADRB3-blocker SR59230A and the unselective ADRB1 and 2-blocker propranolol for 4 weeks. A vehicle (VEH) and non-tumor bearing (NTB) group was also used. Significant effects were seen on total body weight loss with SR-treatment compared to VEH. Similar effects were seen on the wasting of local WAT depots. When measuring body composition, we found moderate evidence that SR spares the wasting of lean mass. We were also able to show decreased gene expression of BAT-markers, as well as markers for lipolysis, in the subcutaneous WAT. This supports our main hypothesis. In conclusion, we can show that treatment with a selective ADRB3 antagonist alleviates the symptoms of CIC through decreased lipolysis and decreased browning of WAT. These findings add to the mechanistic understanding of the pathophysiology of CIC and could be a potential treatment strategy for this syndrome.

  • 3.
    Cheddad, Abbas
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Nord, Christoffer
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Hörnblad, Andreas
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Prunskaite-Hyyryläinen, Renata
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland.
    Eriksson, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Georgsson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Vainio, Seppo
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland.
    Ahlgren, Ulf
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion2013In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 21, no 14, p. 16584-16604Article in journal (Refereed)
    Abstract [en]

    We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods.

  • 4. Chen, Ye
    et al.
    Wang, Aiguo
    Ding, Huitong
    Que, Xia
    Li, Yabo
    An, Ning
    Jiang, Lili
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    A global learning with local preservation method for microarray data imputation2016In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 77, p. 76-89Article in journal (Refereed)
    Abstract [en]

    Microarray data suffer from missing values for various reasons, including insufficient resolution, image noise, and experimental errors. Because missing values can hinder downstream analysis steps that require complete data as input, it is crucial to be able to estimate the missing values. In this study, we propose a Global Learning with Local Preservation method (GL2P) for imputation of missing values in microarray data. GL2P consists of two components: a local similarity measurement module and a global weighted imputation module. The former uses a local structure preservation scheme to exploit as much information as possible from the observable data, and the latter is responsible for estimating the missing values of a target gene by considering all of its neighbors rather than a subset of them. Furthermore, GL2P imputes the missing values in ascending order according to the rate of missing data for each target gene to fully utilize previously estimated values. To validate the proposed method, we conducted extensive experiments on six benchmarked microarray datasets. We compared GL2P with eight state-of-the-art imputation methods in terms of four performance metrics. The experimental results indicate that GL2P outperforms its competitors in terms of imputation accuracy and better preserves the structure of differentially expressed genes. In addition, GL2P is less sensitive to the number of neighbors than other local learning-based imputation. methods.

  • 5. Enroth, Stefan
    et al.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Gyllensten, Ulf
    Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 12, p. 309-314Article in journal (Refereed)
    Abstract [en]

    The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.

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  • 6.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Turkina, Maria V
    Department of Clinical and Experimental Medicine, Linköpings universitet.
    Carlsson, Anders
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Gerdle, Björn
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Larsson, Britt
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Hellström, Fredrik
    Department of Occupational and Public Health Sciences, Högskolan i Gävle.
    Ghafouri, Bijar
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Myosin light chain and calcium regulating protein differences in chronic musculoskeletal neck and shoulder pain2016In: Journal of Integrated Omnics, ISSN 2182-0287, Vol. 6, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Proteomic screening analysis has detected myosin light chain (MLC) as a protein implied to be involved in chronic musculoskeletal neck and shoulder pain. Several analyses of MLC proteins have stated a difference in phosphorylation being the determining factor for protein activation hence altered contrability of the muscle in i.e. senescence. In continuation of a previous publication, this study is an attempt to analyze the different MLC isoforms by mass spectrometry and immune-analyses in myalgic and healthy trapezius muscle. In the present study no differences in phosphorylation level between the corresponding individual proteins were detected using LC-MSMS and immunoblotting; instead we assigned different isoforms of regulatory MLCs. To further elucidate the contrability: calcium (Ca2+) regulatory proteins, sarco(endo)plasmic reticulum Ca2+ ATPase 1 (SERCA-1) and calsequestrine (CSQ) were analyzed by western blot. The analysis revealed a significantly increased abundance of SERCA-1 protein in the myalgic muscle and a significantly increased abundance of CSQ in healthy muscle. Myalgic muscle contraction patterns have in previous studies shown to differ from healthy muscle which may be connected to the Ca2+ availability in the muscle. Here we present the proteomic characterization of differences in Ca2+ regulating proteins and particularly regulatory MLCs in trapezius muscle of women with chronic musculoskeletal neck and shoulder pain.

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  • 7.
    Karlheden, Rebecka
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Asthma, asthma medication and training intensity in Swedish competitive athletes: An internet-based survey2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 8. Kumar, Abhinav
    et al.
    Bicer, Elif Melis
    Morgan, Anna Babin
    Pfeffer, Paul E.
    Monopoli, Marco
    Dawson, Kenneth A.
    Eriksson, Jonny
    Edwards, Katarina
    Lynham, Steven
    Arno, Matthew
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Somers, Graham
    Hassall, Dave
    Dailey, Lea Ann
    Forbes, Ben
    Mudway, Ian S.
    Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid2016In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 12, no 4, p. 1033-1043Article in journal (Refereed)
    Abstract [en]

    When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semiquantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. From the Clinical Editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. (C) 2016 Published by Elsevier Inc.

  • 9.
    Larsen, Christian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Forchheimer, Robert
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Tu, Deyu
    Design, fabrication and application of organic power converters: Driving light-emitting electrochemical cells from the AC mains2017In: Organic electronics, ISSN 1566-1199, E-ISSN 1878-5530, Vol. 45, p. 57-64Article in journal (Refereed)
    Abstract [en]

    The design, fabrication and operation of a range of functional power converter circuits, based on diode configured organic field-effect transistors as the rectifying unit and capable of transforming a high AC input voltage to a selectable DC voltage, are presented. The converter functionality is demonstrated by selecting and tuning its constituents so that it can effectively drive a low-voltage organic electronic device, a light-emitting electrochemical cell (LEC), when connected to high-voltage AC mains. It is established that the preferred converter circuit for this task comprises an organic full-wave rectifier and a regulation resistor but is void of a smoothing capacitor, and that such a circuit connected to the AC mains (230 V, 50 Hz) successfully can drive an LEC to bright luminance (360 cd m(-2)) and high efficiency (6.4 cd A(-1)).

  • 10.
    Larsson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    An Analysis of XCR1 in GFAP+ Glial Cells Throughout the Brain and Brainstem using Karma mice2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 11. Zammit, Carla M.
    et al.
    Mangold, Stefanie
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Jonna, Venkateswara Rao
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Mutch, Lesley A.
    Watling, Helen R.
    Dopson, Mark
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Watkin, Elizabeth L. J.
    Bioleaching in brackish waters-effect of chloride ions on the acidophile population and proteomes of model species2012In: Applied Microbiology and Biotechnology, ISSN 0175-7598, E-ISSN 1432-0614, Vol. 93, no 1, p. 319-329Article in journal (Refereed)
    Abstract [en]

    High concentrations of chloride ions inhibit the growth of acidophilic microorganisms used in biomining, a problem particularly relevant to Western Australian and Chilean biomining operations. Despite this, little is known about the mechanisms acidophiles adopt in order to tolerate high chloride ion concentrations. This study aimed to investigate the impact of increasing concentrations of chloride ions on the population dynamics of a mixed culture during pyrite bioleaching and apply proteomics to elucidate how two species from this mixed culture alter their proteomes under chloride stress. A mixture consisting of well-known biomining microorganisms and an enrichment culture obtained from an acidic saline drain were tested for their ability to bioleach pyrite in the presence of 0, 3.5, 7, and 20 g L(-1) NaCl. Microorganisms from the enrichment culture were found to out-compete the known biomining microorganisms, independent of the chloride ion concentration. The proteomes of the Gram-positive acidophile Acidimicrobium ferrooxidans and the Gram-negative acidophile Acidithiobacillus caldus grown in the presence or absence of chloride ions were investigated. Analysis of differential expression showed that acidophilic microorganisms adopted several changes in their proteomes in the presence of chloride ions, suggesting the following strategies to combat the NaCl stress: adaptation of the cell membrane, the accumulation of amino acids possibly as a form of osmoprotectant, and the expression of a YceI family protein involved in acid and osmotic-related stress.

  • 12.
    Åstrand, Anders P
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Jalkanen, Ville
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Andersson, Britt M
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindahl, Olof A
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Detection of stiff nodules embedded in soft tissue phantoms, mimicking cancer tumours, using a tactile resonance sensor2014In: Journal of Biomedical Science and Engineering, ISSN 1937-6871, E-ISSN 1937-688X, Vol. 7, p. 181-193Article in journal (Refereed)
    Abstract [en]

    Background

    Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the prostate is histopathologically analysed. One area of interest is to examine the capsule of the prostate, as tumours on and near the surface can indicate that the PCa has spread to other parts of the body. There are no current methods to examine the surface of the prostate at the time of surgery. Tactile resonance sensors can be used for detecting areas of different stiffness in soft tissue. Human prostate tissue affected by cancer is usually stiffer than healthy tissue, and for this purpose a tactile resonance sensor was developed. The aim of this study was to investigate the depth at which embedded stiffer volumes could be detected, using soft tissue phantoms.

    Methods

    With the tactile resonance sensor used in this study, the shift of the resonance frequency and the force at contact with tissue can be measured, and combined into a tissue stiffness parameter. The detection sensitivity of the sensor at impression depths, 0.4 and 0.8 mm, was measured for detection of an inserted nodules of stiff silicone in softer silicone and in chicken muscle tissue, mimicking prostate tissue with cancer tumours.

    Results

    Measurements on the silicone samples detected the hidden stiffer object at a depth of 1-4 mm with a difference in the stiffness parameter of 80 – 900 mN/kHz (p < 0.028, n = 48). At the depth 5-6 mm the difference was smaller but still significant < 30 mN/kHz (p < 0.05, n = 24). For the measurements on chicken muscle, the detectable depth was 4 mm (p < 0.05, n = 24).

    Conclusion

    This model study suggests that, with only a small impression depth of ≤ 1 mm, the resonance sensor system described here can detect stiffness variations located at least 4 mm in silicone and chicken muscle, mimicking tumours in prostate tissue.

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