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1.	Molin, Mikael, 1973, et al. (författare) Protein kinase A controls yeast growth in visible light 2020 Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1 Tidskriftsartikel (refereegranskat)abstract Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
2.	Geli Rolfhamre, Patricia, 1979- (författare) From Penicillin Binding Proteins to Community Interventions : Mathematical and Statistical Models Related to Antibiotic Resistance 2009 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Antibiotic resistance has become a major public health concern and mathematical models are important analytical tools for the understanding, evaluation and prediction of the resistance problem and related control strategies.The risk of emerging antibiotic resistance and selection has rarely been a concern in the design of antibiotic drug dosing regimens. In the first paper, a selection of antibiotic resistant subpopulations for different antibiotic dosing regimens was studied in vitro. The demonstrated complex relationship was influenced by both the rise of new mutants and a postantibiotic effect (PAE) (continued inhibition of bacterial growth after removal of the antibiotic drug). By constructing a mathematical model that incorporated biologically relevant parameters, we were able to assess the risks of resistance development under different dosing strategies.In the second paper, the model for PAEs is further developed to determine the implications for different dosing regimens. The result challenges the conventional notion that long PAEs promote extended drug dosing intervals and it allows new hypotheses to be tested experimentally based on the findings from the theoretical framework.Since PAE experiments often are time-consuming and laborious, very few studies have been reporting variation for this phenomenon. In the third paper, an extension to capture the stochastic behavior of bacterial population growth under drug exposure is made. The stochastic nature of the model is also an important complement to the existing deterministic models on drug dose drug effect relationships.The last paper describes a controlled clinical intervention study aiming at determining whether the frequency of trimethoprim resistance in E. coli can be decreased by a sudden and drastic reduction in trimethoprim use. In addition to evaluating the intervention effect, the model, given estimated parameters, is also used for predicting other interesting outcomes.
3.	Hanzén, Sarah, et al. (författare) Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins 2016 Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 166:1, s. 140-151 Tidskriftsartikel (refereegranskat)abstract Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.
4.	Ivanov, Sergey, et al. (författare) Temperature-dependent structural and magnetic properties of R2MMnO6 double perovskites (R=Dy, Gd; M=Ni, Co) 2018 Ingår i: Journal of Materials Science: Materials in Electronics. - : Springer Science and Business Media LLC. - 1573-482X .- 0957-4522. ; 29:21, s. 18581-18592 Tidskriftsartikel (refereegranskat)abstract The structural and magnetic properties of the Dy2CoMnO6, Dy2NiMnO6 and Gd2CoMnO6 double perovskites are investigated using X-ray powder diffraction and squid magnetometry. The materials adopt an orthorhombic structure (space ground Pnma) with disordered Co(Ni)/Mn cations, and exhibit ferrimagnetic transitions near T(C)85, 95, and 115K respectively. T-C was found to monotonously depend on the orthorhombic distortion (a-c)/(a+c) of the compounds. The crystal structure of the compounds was investigated as a function of temperature (16-1100K range), evidencing changes in the BO6 octahedron near T-C. The magnetic entropy changes are estimated for comparison of the magnetocaloric properties to those from literature.
5.	Logg, Katarina, 1979, et al. (författare) High-throughput Growth Measurements of Yeast Exposed to Visible Light 2022 Ingår i: Bio-Protocol. - 2331-8325. ; 12:2 Tidskriftsartikel (refereegranskat)abstract Light is a double-edged sword: it is essential for life on the planet but also causes cellular damage and death. Consequently, organisms have evolved systems not only for harvesting and converting light energy into chemical energy but also for countering its toxic effects. Despite the omnipresence and importance of such light-dependent effects, there are very few unbiased genetic screens, if any, investigating the mechanistic consequences that visible light has on cells. Baker's yeast, Saccharomyces cerevisiae, is one of the best annotated organisms thanks to several easily available mutant collections and its amenability to high-throughput genetic screening. However, until recently this yeast was thought to lack receptors for visible light, therefore its response to visible light was poorly understood. Nevertheless, a couple of years ago it was discovered that yeast senses light via a novel and unconventional pathway involving a peroxisomal oxidase, hydrogen peroxide, and a particular type of antioxidant protein, called peroxiredoxin. Here, we describe in detail a protocol for scoring yeast genes involved in the resistance to visible light (400-700 nm) on a genome-wide scale. Because cells in dense cultures shield each other from light exposure, resulting in apparent light resistance, our method involves adaptations to reduce inoculum size under conditions amenable to high-throughput screens, to properly be able to identify light-sensitive mutants. We also describe how to measure growth in the presence of light, including two follow-up validation tests. In this way, this method makes it possible to score light-sensitivity on a genome-wide scale with high confidence.
6.	Svensson, Mattias, 1982, et al. (författare) Fms-like tyrosine kinase 3 ligand controls formation of regulatory T cells in autoimmune arthritis. 2013 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Fms-like tyrosine kinase 3 ligand (Flt3L) is known as the primary differentiation and survival factor for dendritic cells (DCs). Furthermore, Flt3L is involved in the homeostatic feedback loop between DCs and regulatory T cell (Treg). We have previously shown that Flt3L accumulates in the synovial fluid in rheumatoid arthritis (RA) and that local exposure to Flt3L aggravates arthritis in mice, suggesting a possible involvement in RA pathogenesis. In the present study we investigated the role of Flt3L on DC populations, Tregs as well as inflammatory responses in experimental antigen-induced arthritis. Arthritis was induced in mBSA-immunized mice by local knee injection of mBSA and Flt3L was provided by daily intraperitoneal injections. Flow cytometry analysis of spleen and lymph nodes revealed an increased formation of DCs and subsequently Tregs in mice treated with Flt3L. Flt3L-treatment was also associated with a reduced production of mBSA specific antibodies and reduced levels of the pro-inflammatory cytokines IL-6 and TNF-α. Morphological evaluation of mBSA injected joints revealed reduced joint destruction in Flt3L treated mice. The role of DCs in mBSA arthritis was further challenged in an adoptive transfer experiment. Transfer of DCs in combination with T-cells from mBSA immunized mice, predisposed naïve recipients for arthritis and production of mBSA specific antibodies. We provide experimental evidence that Flt3L has potent immunoregulatory properties. Flt3L facilitates formation of Treg cells and by this mechanism reduces severity of antigen-induced arthritis in mice. We suggest that high systemic levels of Flt3L have potential to modulate autoreactivity and autoimmunity.
7.	Andersson, Anna, et al. (författare) Lactate contributes to ammonia-mediated astroglial dysfunction during hyperammonemia. 2009 Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 34:3, s. 556-65 Tidskriftsartikel (refereegranskat)abstract Even though ammonia is considered to underlie nervous system symptoms of dysfunction during hyperammonemia, lactate, which increases as a metabolic consequence of high ammonia levels, might also be a contributing factor. The data presented here show that NH4Cl (5 mM) mediates astroglial cell swelling, and that treatment with NH4Cl or lactate (25 mM) causes rearrangements of actin filaments and reduces astroglial glutamate uptake capacity. Co-application with BaCl2, which blocks astroglial uptake of NH4+, prevents NH4Cl-mediated cell swelling and rearrangement of actin filaments, but does not reduce NH4Cl-induced glutamate uptake capacity inhibition. Neither NH4Cl nor lactate affected glutamate uptake or protein expression in microglial cultures, indicating that astroglial cells are more susceptible to the neurotoxic affects of ammonia. Our results suggest that ammonium underlies brain edema, but that lactate can contribute to some of the cellular dysfunctions associated with elevated cerebral levels of ammonia.
8.	Andersson, Daniel, 1979, et al. (författare) Liquid biopsy analysis in cancer diagnostics. 2020 Ingår i: Molecular aspects of medicine. - : Elsevier BV. - 1872-9452 .- 0098-2997. ; 72 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
9.	Andersson, Henrik, et al. (författare) Traffic noise effects of property prices : hedonic estimates based on multiple noise indicators 2015 Rapport (övrigt vetenskapligt/konstnärligt)abstract Valuation of traffic noise abatement based on hedonic pricing models of the property market has traditionally measured the noise as the equivalent, or another average, level. What is not captured in such a noise indicator is the maximum noise level of a vehicle passage. In this study, we incorporate the maximum noise level in the hedonic model letting the property price depend on both the equivalent noise level and the maximum noise level. Hedonic models for both rail and road noise are estimated. Data consists of characteristics of sold properties, property-specific noise calculation, and geographical variables.We use the hedonic approach to estimate the marginal willingness to pay (WTP) for maximum noise abatement where we model the effect as the maximum noise level subtracted with the equivalent noise level. Furthermore, we control for the equivalent noise level in the estimations. The estimated results show that including the maximum noise level in the model has influence on the property prices, but only for rail and not for road. This means that for road we cannot reject the hypothesis that WTP for noise abatement is based on the equivalent noise level only. For rail, on the other hand, we estimate the marginal WTP for the maximum noise level and it turns out to be substantial. Also, the marginal WTP for the equivalent noise levels seems to be unaffected by the inclusion of the maximum noise level in the model. More research of this novel topic is requested though.
10.	Andersson, Louise, 1979, et al. (författare) Role of EphA4 receptor signaling in thyroid development: regulation of folliculogenesis and propagation of the C-cell lineage. 2011 Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 152:3, s. 1154-64 Tidskriftsartikel (refereegranskat)abstract Transcriptome analysis revealed that the tyrosine kinase receptor EphA4 is enriched in the thyroid bud in mouse embryos. We used heterozygous EphA4-EGFP knock-in mice in which enhanced green fluorescent protein (EGFP) replaced the intracellular receptor domain (EphA4(+/EGFP)) to localize EphA4 protein in thyroid primordial tissues. This showed that thyroid progenitors originating in the pharyngeal floor express EphA4 at all embryonic stages and when follicles are formed in late development. Also, the ultimobranchial bodies developed from the pharyngeal pouch endoderm express EphA4, but the ultimobranchial epithelium loses the EGFP signal before it merges with the median thyroid primordium. Embryonic C cells invading the thyroid are exclusively EphA4-negative. EphA4 expression continues in the adult thyroid. EphA4 knock-out mice and EphA4-EGFP homozygous mutants are euthyroid and have a normal thyroid anatomy but display subtle histological alterations regarding number, size, and shape of follicles. Of particular interest, the pattern of follicular abnormality differs between EphA4(-/-) and EphA4(EGFP/EGFP) thyroids. In addition, the number of C cells is reduced by >50% exclusively in animals lacking EphA4 forward signaling (EphA4(EGFP/EGFP)). Heterozygous EphA4 mutants have no apparent thyroid phenotype. We conclude that EphA4 is a novel regulator of thyroid morphogenesis that impacts on postnatal development of the two endocrine cell lineages of the differentiating gland. In this process both EphA4 forward signaling (in the follicular epithelium) and reverse signaling mediated by its cognate ligand(s) (A- and/or B-ephrins expressed in follicular cells and C cells, respectively) are probably functionally important.
11.	Andersson, Mikael, 1979- (författare) Assessing Physical Activity and Physical Capacity in Subjects with Chronic Obstructive Pulmonary Disease 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The overall aim of this thesis was to assess measurement properties of methods suitable for screening or monitoring of physical capacity and physical activity in subjects with chronic obstructive pulmonary disease (COPD), and to explore factors associated with physical activity levels.Methods: Four observational studies were conducted. Participants in studies I-III (sample sizes) (n=49, n=15, n=73) were recruited from specialist clinics, and in study IV from a population-based cohort (COPD n=470 and Non-COPD n=659). Psychometric properties of methods assessing physical capacity (study I) and physical activity (study II) were investigated in laboratory settings. Daily physical activity and clinical characteristics were assessed with objective methods (study III) and with subjective methods (study IV).Results: Physical capacity as measured by walking speed during a 30-metre walk test displayed high test-retest correlations (ICC>0.87) and small measurement error. The accuracy for step count and body positions differed between activity monitors and direct observations. In study III 92% of subjects had an activity level below what is recommended in guidelines. Forty five percent of subjects’ activity could be accounted for by clinical characteristics with lung function (22.5%), walking speed (10.1%), quadriceps strength (7.0%) and fat-free mass index (3.0%) being significant predictors. In study IV, low physical activity was significantly more prevalent in COPD subjects from GOLD grade ≥II than among Non-COPD subjects (22.4 vs. 14.6%, p = 0.016). The strongest factors associated with low activity in COPD subjects were a history of heart disease, OR (CI 95%) 2.11 (1.10-4.08) and fatigue, OR 2.33 (1.31-4.13) while obesity was the only significant factor in Non-COPD subjects, OR 2.26 (1.17-4.35).Conclusion: The 30 meter walk test and activity monitors are useful when assessing physical capacity and physical activity, respectively in patients with COPD. Impaired physical activity in severe COPD is related to low lung function, low walking speed, low muscle strength and altered body composition, whereas comorbidities and fatigue are linked to insufficient physical activity in patients with moderately severe COPD.
12.	Andersson, M., et al. (författare) Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis 2023 Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 64:1, s. 32-41 Tidskriftsartikel (refereegranskat)abstract Background Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. Purpose To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. Material and Methods A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. Results The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). Conclusion DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.
13.	Andersson, Mikael, 1979- (författare) Physical activity and physical capacity in subjects with chronic obstructive pulmonary disease 2017 Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 5:sup1 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
14.	Andersson, Veronica, 1979, et al. (författare) Enhancing protein disaggregation restores proteasome activity in aged cells 2013 Ingår i: Aging-Us. - 1945-4589. ; 5:11, s. 802-812 Tidskriftsartikel (refereegranskat)abstract The activity of the ubiquitin-proteasome system, UPS, declines during aging in several multicellular organisms. The reason behind this decline remains elusive. Here, using yeast as a model system, we show that while the level and potential capacity of the 26S proteasome is maintained in replicatively aged cells, the UPS is not functioning properly in vivo. As a consequence cytosolic UPS substrates, such as Delta ssCPY* are stabilized, accumulate, and form inclusions. By integrating a pGPD-HSP104 recombinant gene into the genome, we were able to constitutively elevate protein disaggregase activity, which diminished the accumulation of protein inclusions during aging. Remarkably, this elevated disaggregation restored degradation of a 26S proteasome substrate in aged cells without elevating proteasome levels, demonstrating that age-associated aggregation obstructs UPS function. The data supports the existence of a negative feedback loop that accelerates aging by exacerbating proteostatic decline once misfolded and aggregation-prone proteins reach a critical level.
15.	Aramrattana, Maytheewat, 1988-, et al. (författare) Remote Driving Operation (REDO) project : final report 2023 Rapport (övrigt vetenskapligt/konstnärligt)abstract This report presents experimental setups and findings from the REDO project, which had been conducted between December 2019 and February 2023. Five main topics are covered in this report: 1) Effects of latency and field-of-view on driving performance; 2) Remote driving feedback and control; 3) Connectivity and mobile network support for remote driving; 4) Video transmission for remote driving; and 5) Laws and regulations concerning remote driving. Contents of this report dives into technical details and findings within each topic. Nevertheless, this report does not intend to repeat all detail and results published in scientific publications, and thus this report should be seen as complementary material to the published results.
16.	Bergh, Niklas, 1979, et al. (författare) A new biomechanical perfusion system for ex vivo study of small biological intact vessels 2005 Ingår i: Ann Biomed Eng. - : Springer Science and Business Media LLC. - 0090-6964. ; 33:12, s. 1808-18 Tidskriftsartikel (refereegranskat)abstract The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.
17.	Dehlin, Mats, 1968, et al. (författare) Inhibition of fms-like tyrosine kinase 3 alleviates experimental arthritis by reducing formation of dendritic cells and antigen presentation. 2011 Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 90:4, s. 811-7 Tidskriftsartikel (refereegranskat)abstract TKs are intracellular signaling molecules essential for cell homeostasis. Inhibition of TKs is used in treatment of malignancies and diabetes mellitus. The present study evaluated the role of Flt3 in antigen-induced arthritis. Mice were immunized with mBSA, and arthritis was induced by an i.a. injection of mBSA. Treatment with the Flt3 inhibitor sunitinib was started together with mBSA immunization or together with the induction of arthritis. The mBSA-injected joints were evaluated morphologically for signs of synovitis and bone/cartilage destruction. Markers of bone metabolism and antibody responses were measured by ELISA. Maturation of DCs in the bone marrow and spleen was evaluated by flow cytometry. Sunitinib treatment reduced the intensity of synovitis and the incidence of bone destruction. The reduction in bone destruction was seen when the treatment was started at the time of immunization or at the time of arthritis induction. The antiarthritic effect was achieved by inhibition of DCs, reduction of antibody production, and bone metabolism. Inhibition of Flt3 is a potent antiarthritic mechanism reducing antigen presentation, synovial inflammation, and bone resorption. Down-regulation of TKs may be a useful tool in the treatment of human RA.
18.	Fagman, Henrik, 1975, et al. (författare) The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation. 2006 Ingår i: Developmental dynamics : an official publication of the American Association of Anatomists. - : Wiley. - 1058-8388. ; 235:2, s. 444-55 Tidskriftsartikel (refereegranskat)abstract Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.
19.	Gil Gómez, Gaspar, et al. (författare) Validation of a Moving Base Driving Simulator for Subjective Assessments of Steering Feel and Handling 2017 Ingår i: 13th International Symposium on Advanced Vehicle Control. - : CRC Press/Balkema. - 9781315265285 ; , s. 431-436 Konferensbidrag (refereegranskat)abstract Moving Base Driving Simulators (MBDS) have a large potential to increase effectiveness in vehicle dynamics development. MBDS can reduce dependency on vehicle-prototypes by allowing subjective assessments (SA) of models. Little is, however, known about the relation of SA in MBDS and in physical ve- hicles. This paper aims to increase this knowledge, and proposes and implements a methodology to validate MBDS for SA of steering feel and handling. Firstly, vehicle models were generated from Kinematics & Com- pliance measurements of real vehicles. These models were validated versus objective tests, with steering ro- bots, of the physical vehicles. These vehicles and their MBDS-models were assessed by expert drivers, using a scanned-test track in the MBDS. Comparison of the SA in both environments enabled the MBDS validation. Promising results, with higher SA accuracy for handling than for steering feel, indicates that the major im- provement effort should focus on the steering model and its simulation in the MBDS.
20.	Hedberg, Suzanne, et al. (författare) Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass : A Randomized Clinical Trial 2024 Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:1 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE: Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear.OBJECTIVE: To compare perioperative outcomes in SG and RYGB.DESIGN, SETTING, AND PARTICIPANTS: In this registry-based, multicenter randomized clinical trial (Bypass Equipoise Sleeve Trial), baseline and perioperative data for patients undergoing bariatric surgery from October 6, 2015, to March 31, 2022, were analyzed. Patients were from university, regional, county, and private hospitals in Sweden (n = 20) and Norway (n = 3). Adults (aged ≥18 years) eligible for bariatric surgery with body mass indexes (BMIs; calculated as weight in kilograms divided by height in meters squared) of 35 to 50 were studied.INTERVENTIONS: Laparoscopic SG or RYGB.MAIN OUTCOMES AND MEASURES: Perioperative complications were analyzed as all adverse events and serious adverse events (Clavien-Dindo grade >IIIb). Ninety-day mortality was also assessed.RESULTS: A total of 1735 of 14 182 eligible patients (12%; 1282 [73.9%] female; mean (SD) age, 42.9 [11.1] years; mean [SD] BMI, 40.8 [3.7]) were included in the study. Patients were randomized and underwent SG (n = 878) or RYGB (n = 857). The mean (SD) operating time was shorter in those undergoing SG vs RYGB (47 [18] vs 68 [25] minutes; P < .001). The median (IQR) postoperative hospital stay was 1 (1-1) day in both groups. The 30-day readmission rate was 3.1% after SG and 4.0% after RYGB (P = .33). There was no 90-day mortality. The 30-day incidence of any adverse event was 40 (4.6%) and 54 (6.3%) in the SG and RYGB groups, respectively (odds ratio, 0.71; 95% CI, 0.47-1.08; P = .11). Corresponding figures for serious adverse events were 15 (1.7%) for the SG group and 23 (2.7%) for the RYGB group (odds ratio, 0.63; 95% CI, 0.33-1.22; P = .19).CONCLUSIONS AND RELEVANCE: This randomized clinical trial of 1735 patients undergoing primary bariatric surgery found that both SG and RYGB were performed with a low perioperative risk without clinically significant differences between groups.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02767505.
21.	IVIM reveals increased blood perfusion of liver metastases after oral intake of Salovum® 2015 Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. Proceedings (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract Introduction Elevated interstitial fluid pressure (IFP) of tumours impairs perfusion, which hinders anti-cancer drugs and oxygen to reach tumour cells1-3. AF-16, a 16 amino acid long sequence from the amino terminal end of the endogenous protein Antisecretory Factor (AF), supresses IFP in animal models of solid tumours4, and could improve drug delivery to tumour cells. Salovum®, a spray-dried egg yolk powder with high content of antisecretory peptides, should be tested on humans, but requires non-invasive tumour IFP/perfusion assessment methods. The IntraVoxel Incoherent Motion (IVIM) model applied to multi-b DWI enables measurement of tissue diffusion (D), pseudo-diffusion (D*) and voxel volume fraction of actively perfused capillaries (f) 5. The aim of this study was to investigate if f could be used to monitor changes induced by Salovum® in colorectal liver metastases in vivo Subjects and Methods Previously untreated patients (n=6) with colorectal liver metastases were imaged before, and 24h after intake of Salovum®, using IVIM-MRI (3T Philips, 16‐channel receiver; Single-shot, SE‐EPI (breath-hold); FOV covering liver, 3x3x5mm3 voxels; TR/TE/NSA/SENSE=1900ms/50ms/2/2; 11 b‐values (0-600); acquisition~10 min. MATLAB-based images processing comprised 1) Inter-scan image registration (volume preserving free-form deformation6); 2) Voxelwise fitting of D and A [eq.2] to S(b200-600) (for b>200, [eq.1] reduces to [eq.2], assuming D<2cm) on DWI (b=600), transfer of ROIs to corresponding f-maps for calculation of median ROI f before and after Salovum® intake and 4) Mann-Whitney U-test for statistical significance (α-level=0.05). Results Liver and metastases were well visualised on DWIs and f-maps Median f in metastatic tissue increased after intake of Salovum® in 5/6 patients, but decreased in one patient (Fig.2) (p<0.0001). Discussion/Conclusion The increased perfusion fraction on day 2 may offer a “window of opportunity” for improved transport of drugs to tumour cells. The increase in f was small, and perhaps not clinically significant, suggesting that additional time points after Salovum® intake and dose escalation be investigated, as well as intra-tumour effect heterogeneity. The proposed IVIM approach is a promising, non-invasive method for studying Salovum® induced changes in liver metastases in vivo. Further optimisation and fractionation studies should be conducted, and IVIM derived parameters should be compared to other techniques for perfusion or IFP measurements. References 1Rofstad,E.K.,et al.,Neoplasia. 2009;11(11):1243-51. 2Milosevic,M.F.,et al.,1999;43(5):1111-23. 3Wiig, H.,et al.,1982;42(2):159-64. 4Al-Olama, M.et al., 2011;50(7):1098-104. 5Le Bihan, D., et al., 1988;168(2):497-505. 6Rueckert, D., et al., 1999;18(8):712-21.
22.	Jalnefjord, Oscar, 1989, et al. (författare) Comparison of methods for estimation of the intravoxel incoherent motion (IVIM) diffusion coefficient (D) and perfusion fraction (f) 2018 Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 31:6, s. 715-723 Tidskriftsartikel (refereegranskat)abstract Objective: Intravoxel incoherent motion (IVIM) shows great potential in many applications, e.g., tumor tissue characterization. To reduce image-quality demands, various IVIM analysis approaches restricted to the diffusion coefficient (D) and the perfusion fraction (f) are increasingly being employed. In this work, the impact of estimation approach for D and f is studied. Materials and methods: Four approaches for estimating D and f were studied: segmented IVIM fitting, least-squares fitting of a simplified IVIM model (sIVIM), and Bayesian fitting of the sIVIM model using marginal posterior modes or posterior means. The estimation approaches were evaluated in terms of bias and variability as well as ability for differentiation between tumor and healthy liver tissue using simulated and in vivo data. Results: All estimation approaches had similar variability and ability for differentiation and negligible bias, except for the Bayesian posterior mean of f, which was substantially biased. Combined use of D and f improved tumor-to-liver tissue differentiation compared with using D or f separately. Discussion: The similar performance between estimation approaches renders the segmented one preferable due to lower numerical complexity and shorter computational time. Superior tissue differentiation when combining D and f suggests complementary biologically relevant information.
23.	Jalnefjord, Oscar, 1989, et al. (författare) IVIM D and f - Optimal estimation technique and their potential for tissue differentiation 2018 Ingår i: Joint Annual Meeting ISMRM-ESMRMB, 26-21 June 2018, Paris. - : International Society för Magnetic Resonance in Medicine. Konferensbidrag (refereegranskat)
24.	Johansson, Ellen, et al. (författare) Asynchrony of Apical Polarization, Luminogenesis, and Functional Differentiation in the Developing Thyroid Gland 2021 Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12 Tidskriftsartikel (refereegranskat)abstract Follicular thyroid tissue originates from progenitors derived from a midline endodermal primordium. Current understanding infers that folliculogenesis in the embryonic thyroid designates the latest morphogenetic event taking place after the final anatomical shape and position of the gland is established. However, this concept does not consider the fact that the thyroid isthmus develops chronologically before the lobes and also contains all progenitors required for lobulation. To elucidate whether cells committed to a thyroid fate might be triggered to differentiate asynchronously related to maturation and developmental stage, mouse embryonic thyroid tissues from E12.5-17.5 were subjected to immunofluorescent labeling of biomarkers (progenitors: NKX2-1; differentiation: thyroglobulin/TG); folliculogenesis: E-cadherin/CDH1; luminogenesis: mucin 1/MUC1; apical polarity: pericentrin/PCNT; basement membrane: laminin; growth: Ki67), quantitative RT-PCR analysis (Nkx2.1, Tg, Muc1) and transmission electron microscopy. Tg expression was detectable as early as E12.5 and gradually increased >1000-fold until E17.5. Muc1 and Nkx2.1 transcript levels increased in the same time interval. Prior to lobulation (E12.5-13.5), MUC1 and TG distinguished pre-follicular from progenitor cells in the developing isthmus characterized by intense cell proliferation. Luminogenesis comprised redistribution of MUC1+ vesicles or vacuoles, transiently associated with PCNT, to the apical cytoplasm and the subsequent formation of MUC1+ nascent lumens. Apical polarization of pre-follicular cells and lumen initiation involved submembraneous vesicular traffic, reorganization of adherens junctions and ciliogenesis. MUC1 did not co-localize with TG until a lumen with a MUC1+ apical membrane was established. MUC1 delineated the lumen of all newly formed follicles encountered in the developing lobes at E15.5-17.5. Folliculogenesis started before establishment of a complete follicular basal lamina. These observations indicate that embryonic thyroid differentiation is an asynchronous process consistent with the idea that progenitors attaining a stationary position in the connecting isthmus portion undergo apical polarization and generate follicles already at a primordial stage of thyroid development, i.e. foregoing growth of the lobes. Although the thyroid isthmus eventually comprises minute amounts of the total thyroid volume and contributes little to the overall hormone production, it is of principal interest that local cues related to the residence status of cells – independently of a prevailing high multiplication rate – govern the thyroid differentiation program. Copyright © 2021 Johansson, Liang, Moccia, Carlsson, Andersson, Fagman and Nilsson.
25.	Johansson, Ellen, et al. (författare) Revising the embryonic origin of thyroid C cells in mice and humans 2015 Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 142:20, s. 3519-3528 Tidskriftsartikel (refereegranskat)abstract Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate-mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development implicates a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. In similarity with many gut endoderm derivatives embryonic C cells were found to co-express pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo consistent with a growth-promoting role of Foxa1. Contrasting embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment down-regulated Foxa2 foregoing epithelial-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm, and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.
26.	Khan, Omar M., 1980, et al. (författare) Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice. 2011 Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39 Tidskriftsartikel (refereegranskat)abstract RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
27.	Laudette, Marion, et al. (författare) Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function 2023 Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1537-1552 Tidskriftsartikel (refereegranskat)abstract Aims Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CMPcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. Methods and results Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. Conclusion PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
28.	Li, Lizhen, 1977, et al. (författare) Protective role of reactive astrocytes in brain ischemia. 2008 Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 28:3, s. 468-81 Tidskriftsartikel (refereegranskat)abstract Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP(-/-)Vim(-/-) mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery (MCA) transection, infarct volume was 210 to 350% higher in GFAP(-/-)Vim(-/-) than in wild-type (WT) mice; GFAP(-/-), Vim(-/-) and WT mice had the same infarct volume. Endothelin B receptor (ET(B)R) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/-)Vim(-/-) astrocytes. In WT astrocytes, ET(B)R colocalized extensively with bundles of IFs. GFAP(-/-)Vim(-/-) astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP(-/-)Vim(-/-) than in WT mice. DNA array analysis and quantitative real-time PCR showed downregulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ET(B)R-mediated control of gap junctions, and PAI-1 expression.
29.	Melander, Anders, 1962-, et al. (författare) Hoshin Kanri : Innovativ ledning av strategiarbete 2020. - 1 Bok (övrigt vetenskapligt/konstnärligt)
30.	Merkel, Magnus, et al. (författare) Automatic Extraction and Manual Validation of Hierarchical Patent Terminology 2009 Ingår i: NORDTERM 16. Ontologier og taksonomier.. - Copenhagen, Denmark : Copenhagen Business School Press. - 9788799457700 ; , s. 249-262 Konferensbidrag (refereegranskat)abstract Several methods can be applied to create a set of validated terms from existing documents. In this paper we describe an automatic bilingual term candidate extraction method, and the validation process used to create a hierarchical patent terminology. The process described was used to extract terms from patent texts, commissioned by the Swedish Patent Office with the purpose of using the terms for machine translation. Information on the correct linguistic inflection patterns and hierarchical partitioning of terms based on their use are of utmost importance.The process contains six phases, 1) Analysis of the source material and system configuration; 2) Term candidate extraction; 3) Term candidate filtering and initial linguistic validation; 4) Manual validation by domain experts; 5) Final linguistic validation; and 6) Publishing the validated terms.Input to the extraction process consisted of more than 91 000 patent document pairs in English and Swedish, 565 million words in English and 450 million words in Swedish. The English documents were supplied in EBD SGML format and the Swedish documents were supplied in OCR processed scans of patent documents. After grammatical and statistical analysis, the documents were word-aligned. Using the word-aligned material, candidate terms were extracted based on linguistic patterns. 750 000 term candidates were extracted and stored in a relational database. The term candidates were processed in 8 months resulting in 181 000 unique validated term pairs that were exported into several hierarchically organized OLIF files.
31.	Periyannan Rajeswari, Prem Kumar, et al. (författare) Multiple pathogen biomarker detection using an encoded bead array in droplet PCR 2017 Ingår i: Journal of Microbiological Methods. - : Elsevier. - 0167-7012 .- 1872-8359. ; 139, s. 22-28 Tidskriftsartikel (refereegranskat)abstract We present a droplet PCR workflow for detection of multiple pathogen DNA biomarkers using fluorescent color coded Luminex beads. This strategy enables encoding of multiple singleplex droplet PCRs using a commercially available bead set of several hundred distinguishable fluorescence codes. This workflow provides scalability beyond the limited number offered by fluorescent detection probes such as TaqMan probes, commonly used in current multiplex droplet PCRs. The workflow was validated for three different Luminex bead sets coupled to target specific capture oligos to detect hybridization of three microorganisms infecting poultry: avian influenza, infectious laryngotracheitis virus and Campylobacter jejuni. In this assay, the target DNA was amplified with fluorescently labeled primers by PCR in parallel in monodisperse picoliter droplets, to avoid amplification bias. The color codes of the Luminex detection beads allowed concurrent and accurate classification of the different bead sets used in this assay. The hybridization assay detected target DNA of all three microorganisms with high specificity, from samples with average target concentration of a single DNA template molecule per droplet. This workflow demonstrates the possibility of increasing the droplet PCR assay detection panel to detect large numbers of targets in parallel, utilizing the scalability offered by the color-coded Luminex detection beads.
32.	Rydén, Mikael, et al. (författare) Lipolysis defect in people with obesity who undergo metabolic surgery 2022 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Inc.. - 0954-6820 .- 1365-2796. ; 292:4, s. 667-678 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Cross-sectional studies demonstrate that catecholamine stimulation of fat cell lipolysis is blunted in obesity. We investigated whether this defect persists after substantial weight loss has been induced by metabolic surgery, and whether it is related to the outcome.DESIGN/METHODS: Patients with obesity not able to successfully reduce body weight by conventional means (n = 126) were investigated before and 5 years after Roux-en-Y gastric bypass surgery (RYGB). They were compared with propensity-score matched subjects selected from a control group (n = 1017), and with the entire group after adjustment for age, sex, body mass index (BMI), fat cell volume and other clinical parameters. Catecholamine-stimulated lipolysis (glycerol release) was investigated in isolated fat cells using noradrenaline (natural hormone) or isoprenaline (synthetic beta-adrenoceptor agonist).RESULTS: Following RYGB, BMI was reduced from 39.9 (37.5-43.5) (median and interquartile range) to 29.5 (26.7-31.9) kg/m2 (p < 0.0001). The post-RYGB patients had about 50% lower lipolysis rates compared with the matched and total series of controls (p < 0.0005). Nordrenaline activation of lipolysis at baseline was associated with the RYGB effect; those with high lipolysis activation (upper tertile) lost 30%-45% more in body weight, BMI or fat mass than those with low (bottom tertile) initial lipolysis activation (p < 0.0007).CONCLUSION: Patients with obesity requiring metabolic surgery have impaired ability of catecholamines to stimulate lipolysis, which remains despite long-term normalization of body weight by RYGB. Furthermore, preoperative variations in the ability of catecholamines to activate lipolysis may predict the long-term reduction in body weight and fat mass.
33.	Sand, Olivia, et al. (författare) Severe pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are common and contribute to decreased overall survival 2021 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:12 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND OBJECTIVES: Extensive abdominal surgery is associated with the risk of postoperative pulmonary complications. This study aims to explore the incidence and risk factors for developing postoperative pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and to analyze how these complications affect overall survival.METHODS: Data were collected on 417 patients undergoing surgery between 2007 and2017 at Uppsala University Hospital, Sweden. Postoperative pulmonary complications were graded according to the Clavien-Dindo classification system where Grade ≥ 3 was considered a severe complication. A logistic regression analysis was used to analyze risk factors for postoperative pulmonary complications and a Cox proportional hazards model to assess impact on survival.RESULTS: Seventy-two patients (17%) developed severe postoperative pulmonary complications. Risk factors were full thickness diaphragmatic injury and/or diaphragmatic resection [OR 5.393, 95% CI 2.924-9.948, p = < 0.001]. Severe postoperative pulmonary complications, in combination with non-pulmonary complications, contributed to decreased overall survival [HR 2.285, 95% CI 1.232-4.241, p = 0.009].CONCLUSIONS: Severe postoperative pulmonary complications were common and contributed to decreased overall survival. Full thickness diaphragmatic injury and/or diaphragmatic resection were the main risk factors. This finding emphasizes the need for further research on the mechanisms behind pulmonary complications and their association with mortality.
34.	Strage, Emma, et al. (författare) Effect of insulin treatment on circulating insulin-like growth factor I and IGF-binding proteins in cats with diabetes mellitus. 2018 Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 32:5, s. 1579-1590 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC) with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to humans, the amount of TC in cats is more variable. Insulin-like growth factor-I concentrations are reported to increase during insulin treatment, more rapidly in cats achieving remission.OBJECTIVES: To investigate (i) factors associated with circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of diabetes mellitus remission.ANIMALS: Thirty-one privately owned diabetic cats of which 24 were followed 1 year, and 13 healthy cats.METHODS: Prospective study. Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF-binding forms were determined by chromatography in 14 diabetic and 13 healthy cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats achieving remission.RESULTS: Insulin-like growth factor-I median (interquartile range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like growth factor-I was positively associated with TC (P < .0001) and endogenous insulin (P = .005) and negatively associated with fructosamine (P < .0001). Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P = .046). In cats that went into remission, the amount of TC and IGFBP-3 increased, suggesting increase in IGF-I is dependent on TC formation.CONCLUSIONS: Insulin treatment should be accounted for when interpreting IGF-I in diabetic cats. Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment shows promise as prognostic marker for remission in diabetic cats.
35.	Strandberg, Louise, 1981, et al. (författare) Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis. 2009 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.
36.	Strandkvist, Viktor, et al. (författare) Hand grip strength is associated with fatigue among men with COPD : epidemiological data from northern Sweden 2020 Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 36:3, s. 408-416 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate if hand grip strength (HGS) is associated with: 1) fatigue, and specifically clinically relevant fatigue (CRF); 2) low physical activity; and 3) fatigue independent of physical activity level, among individuals with and without COPD. Data were collected from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD-study in 2014. HGS was measured with a hand-grip dynamometer, fatigue and physical activity were assessed by questionnaires; FACIT-Fatigue respectively IPAQ. Among individuals with COPD (n = 389), but not without COPD (n = 442), HGS was lower among those with CRF than those without CRF, significantly so among men (p = 0.001) and close to among women (p = 0.051). HGS was not associated with physical activity levels within any of the groups. HGS was associated with fatigue among men, but not women, with COPD independent of physical activity level, age, height, and smoking habits (Beta = 0.190, 95% CI 0.061-0.319, respectively Beta = 0.048, 95% CI-0.056-0.152), while there were no corresponding significant findings among individuals without COPD. In summary, HGS was associated with CRF among individuals with COPD in this population-based study. Among men with COPD, HGS was associated with fatigue independent of physical activity level and common confounders.
37.	Ståhlberg, Anders, 1975, et al. (författare) Defining cell populations with single-cell gene expression profiling: correlations and identification of astrocyte subpopulations. 2011 Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 39:4 Tidskriftsartikel (refereegranskat)abstract Single-cell gene expression levels show substantial variations among cells in seemingly homogenous populations. Astrocytes perform many control and regulatory functions in the central nervous system. In contrast to neurons, we have limited knowledge about functional diversity of astrocytes and its molecular basis. To study astrocyte heterogeneity and stem/progenitor cell properties of astrocytes, we used single-cell gene expression profiling in primary mouse astrocytes and dissociated mouse neurosphere cells. The transcript number variability for astrocytes showed lognormal features and revealed that cells in primary cultures to a large extent co-express markers of astrocytes and neural stem/progenitor cells. We show how subpopulations of cells can be identified at single-cell level using unsupervised algorithms and that gene correlations can be used to identify differences in activity of important transcriptional pathways. We identified two subpopulations of astrocytes with distinct gene expression profiles. One had an expression profile very similar to that of neurosphere cells, whereas the other showed characteristics of activated astrocytes in vivo.
38.	Svec, David, et al. (författare) Direct cell lysis for single-cell gene expression profiling. 2013 Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 3 Tidskriftsartikel (refereegranskat)abstract The interest to analyze single and few cell samples is rapidly increasing. Numerous extraction protocols to purify nucleic acids are available, but most of them compromise severely on yield to remove contaminants and are therefore not suitable for the analysis of samples containing small numbers of transcripts only. Here, we evaluate 17 direct cell lysis protocols for transcript yield and compatibility with downstream reverse transcription quantitative real-time PCR. Four endogenously expressed genes are assayed together with RNA and DNA spikes in the samples. We found bovine serum albumin (BSA) to be the best lysis agent, resulting in efficient cell lysis, high RNA stability, and enhanced reverse transcription efficiency. Furthermore, we found direct cell lysis with BSA superior to standard column based extraction methods, when analyzing from 1 up to 512 mammalian cells. In conclusion, direct cell lysis protocols based on BSA can be applied with most cell collection methods and are compatible with most analytical workflows to analyze single-cells as well as samples composed of small numbers of cells.
39.	Swärdh, Jan-Erik, 1979-, et al. (författare) Värdering och prissättning av järnvägsbuller : sammanfattningav projektresultat 2010 Rapport (övrigt vetenskapligt/konstnärligt)abstract Tystnad är en så kallad icke-marknadsvara, vilket innebär att vi inte kan observera något marknadspris. Dock vet vi att tystnad ger nytta (det vill säga buller åsamkar onytta) och därför efterfrågas av individer. För att erhålla denna nytta har individer således en betalningsvilja, vilket kan uttryckas som efterfrågan för tystnad. I denna rapport sammanfattas på svenska projektet Värdering och prissättning av järnvägsbuller som har genomförts vid VTI och finansierats av Trafikverket (tidigare Banverket). Projektet har syftat till att dels skatta efterfrågan för tystnad (motsatsen till järnvägsbuller) och dels att utifrån denna efterfrågefunktion beräkna marginalkostnader för järnvägsbuller.
40.	Wasén, Caroline, et al. (författare) Smoking activates cytotoxic CD8(+) T cells and causes survivin release in rheumatoid arthritis 2017 Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 78, s. 101-110 Tidskriftsartikel (refereegranskat)abstract CD8(+) T cells have an emerging role in RA. Resent research indicates a causal relationship between the non-exhausted state of CD8(+) T cells, defined by lost function of PD-1, and development of arthritis. We investigated how smoking contributes to the non-exhausted phenotype of CD8(+) T cells and cause survivin release to serum. We compared serum survivin levels between smokers and non-smokers in 252 RA and 168 healthy subjects. Nicotine effects on CD8(+) T cells were studied in peripheral blood of smoking women, bone marrow of nicotine treated mice and in sorted CD8 spleen cells in vitro using flow cytometry and quantitative PCR. Smoking increased the frequency of survivin release in serum of healthy women (OR 3.64, p = 0.025) and in RA patients (OR 1.98, p = 0.039). CD8(+) T cells of smokers gained a non-exhausted PD-1 deficient phenotype. Expression of the cytotoxic marker CD107 correlated to survivin levels in serum. In the experimental setting, nicotine exposure led to an accumulation of non-exhausted PD-1(-)IL-7R(+) CD8(+) T cells in the bone marrow that is abundant with survivin producing cells. The production of the cytolytic protein perforin in bone marrow correlated to serum survivin levels. In vitro stimulation of nicotinic receptors on murine CD8+ T cells induced repressive transcription factors T-bet and Blimp-1 in support of the non-exhausted phenotype. We conclude that nicotine contributes to autoimmunity by supporting the non-exhausted state of CD8+ T cells resulting in the release of survivin. This presents a new mechanism by which smoking may contribute to the pathogenesis of RA. (C) 2016 The Authors. Published by Elsevier Ltd.
41.	Westerlund, Jessica, 1977, et al. (författare) Expression of Islet1 in thyroid development related to budding, migration, and fusion of primordia. 2008 Ingår i: Developmental dynamics : an official publication of the American Association of Anatomists. - : Wiley. - 1058-8388. ; 237:12, s. 3820-9 Tidskriftsartikel (refereegranskat)abstract The LIM homeodomain transcription factor Isl1 was investigated in mouse thyroid organogenesis. All progenitor cells of the midline thyroid diverticulum and lateral primordia (ultimobranchial bodies) expressed Isl1. This pattern persisted until the growing anlagen fused at embryonic day (E) 13.5. In Isl1 null mutants thyroid progenitors expressing Nkx2.1 and Pax8 were readily specified in the anterior endoderm but the size of the thyroid rudiment was reduced. In late development, only immature C-cells expressed Isl1. In the adult gland the number of Isl1+ cells was small compared with cells expressing calcitonin. Analysis of microarray profiles indicated a higher level of Isl1 expression in medullary thyroid carcinomas than in tumors derived from follicular cells. Together, these findings suggest that Isl1 may be a novel regulator of thyroid development before terminal differentiation of the endocrine cell types. Isl1 is an embryonic C-cell precursor marker that may be relevant also in cancer developed from the mature C-cell.
42.	Westerlund, Jessica, 1977, et al. (författare) Misguided migration of C cell precursors to extra-thyroidal locations related to defective pharyngeal pouch development in Shh deficient mice 2013 Ingår i: Cell & Developmental Biology. - 2168-9296. ; 2:4, s. 129-138 Tidskriftsartikel (refereegranskat)abstract A possible role of Sonic hedgehog (Shh) in recruitment of C cell precursors to the ultimobranchial body (UB) and embryonic thyroid was investigated in Shh-/- mice. Nkx2.1 and Foxa2 co-expression distinguished UB originating in the fourth pharyngeal pouch from other derivatives of pharyngeal endoderm. In mutants UB formed a single structure that failed to bud and instead of fusing with the midline thyroid primordium adhered to the thymic rudiments. Mature C cells appeared in the UB remnant and ectopically in the thymic parenchyma, foregut endoderm and trachea. Thyroid did not contain C cells except minute numbers close to the tracheal interface. Tracing progeny in Shh-CRE/Rosa26R mice showed the vast majority of both UB and thyroid progenitors derived from Shh negative endoderm, but Shh expressing cells appeared in both thyroid primordia before fusion of the two. The findings indicate that Shh determines the endoderm territory for C cell differentiation and guides the migration of C cell precursors into the thyroid, presumably by regulating the separation of glandular domains in the pharyngeal pouch endoderm. A cell-autonomous role of Shh in thyroid morphogenesis is suggested.

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