| 1. |
- Allard, Christina, et al.
(author)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby
- 2015
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In: Dagens Nyheter. - 1101-2447.
-
Journal article (pop. science, debate, etc.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 2. |
- Andersson Ersman, Peter, et al.
(author)
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Screen printed digital circuits based on vertical organicelectrochemical transistors
- 2017
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In: Flexible and Printed Electronics. - : IOP Publishing. - 2058-8585. ; 2
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Journal article (peer-reviewed)abstract
- Vertical organic electrochemical transistors (OECTs) have been manufactured solely using screenprinting. The OECTs are based on PEDOT:PSS (poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid)), which defines the active material for both the transistor channel and the gateelectrode. The resulting vertical OECT devices and circuits exhibit low-voltage operation, relativelyfast switching, small footprint and high manufacturing yield; the last three parameters are explainedby the reliance of the transistor configuration on a robust structure in which the electrolyte verticallybridges the bottom channel and the top gate electrode. Two different architectures of the verticalOECT have been manufactured, characterized and evaluated in parallel throughout this report. Inaddition to the experimental work, SPICE models enabling simulations of standalone OECTs andOECT-based circuits have been developed. Our findings may pave the way for fully integrated, lowvoltageoperating and printed signal processing systems integrated with e.g. printed batteries, solarcells, sensors and communication interfaces. Such technology can then serve a low-cost basetechnology for the internet of things, smart packaging and home diagnostics applications.
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| 3. |
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| 4. |
- Appelqvist, Hanna, et al.
(author)
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Specific Imaging of Intracellular Lipid Droplets Using a Benzothiadiazole Derivative with Solvatochromic Properties
- 2017
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In: Bioconjugate Chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 28:5, s. 1363-1370
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Journal article (peer-reviewed)abstract
- Altered lipid metabolism and extensive lipid storage in cells have been associated with various medical disorders, including cancer. The development of fluorescent probes that specifically accumulate in lipid deposits is therefore of great interest in order to study pathological processes that are linked to dysregulated lipogenesis. In the present study, we present a small fluorescent benzothiadiazole dye that specifically stains lipid droplets in living and fixated cells. The photophysical characterization of the probe revealed strong solvatochromic behavior, large Stokes shifts, and high fluorescent quantum yields in hydrophobic solvents. In addition, the fluorophore exhibits a nontoxic profile and a high signal-to-noise ratio in cells (i.e., lipid droplets vs cytosol), which make it an excellent candidate for studying lipid biology using confocal fluorescent microscopy.
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| 5. |
- Berg, Ina, 1982-, et al.
(author)
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Curcumin alleviates Aβ indcuced neurotoxicity and vice versa without removing amyloid deposits in transgenic Drosophila
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Other publication (other academic/artistic)abstract
- Curcumin has been proposed to facilitate clearance of toxic amyloid formed by the Aβ peptide. To further address this notion, different concentrations of curcumin were tried for its effects in various Drosophila Alzheimer’s disease (AD) models. This study entailed five different Drosophila AD models (four Aβ expressing lines, and one tau expressing line), expressing the AD associated proteins using the Gal4/UAS system. These were assayed for several aspects of neurological impairment, including survival, climbing behavior, as well as locomotor activity. In addition, amyloid deposition was assessed by histological analysis. Curcumin treatment substantially prolonged the lifespan and improved climbing and locomotor activity for flies with severe disease geneotypes (Aβ1-42 E22G and double expressing Aβ1-42). In comparison, curcumin feeding of control flies resulted in a concentration-dependent shortened lifespan, whereas no such toxic side effects were found for AD genotypes with a mild phenotype (single expressors of Aβ1-40 and Aβ1-42). All flies expressing Aβ and tau displayed a higher total locomotor activity, and a continuation of the activity over a larger number of hours upon curcumin treatment. Unexpectedly, no change in tissue amyloid deposition upon curcumin treatment was observed. In vitro fibrillation of Aβ1-42, followed by Western blot and transmission electron microscopy in the presence and absence of curcumin, displayed enhanced fibrillation into large aggregates and decreased population of oligomers in curcumin samples. The decrease in oligomer formation by curcumin may explain why it increases the lifespan and activity without removing of the amyloid deposits seen in tissues. We also suggest that Aβ, at least in the context of Drosophila, functions as a chemical detoxifier sequestering curcumin and thereby mitigating its toxicity.
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| 6. |
- Berg, Ina, 1982-, et al.
(author)
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Efficient imaging of amyloid deposits in Drosophila models of human amyloidoses
- 2010
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In: Nature Protocols. - : Macmillan Publishers Ltd.. - 1754-2189 .- 1750-2799. ; 5:5, s. 935-944
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Journal article (peer-reviewed)abstract
- Drosophila melanogaster is emerging as an important model system for neurodegenerative disease research. In this protocol, we describe an efficient method for imaging amyloid deposits in the Drosophila brain, by the use of a luminescent-conjugated oligothiophene (lco), p-Ftaa polymer probe. We also demonstrate the feasibility of co-staining with antibodies and compare the lco staining with standard amyloid-specific probes. the lco protocol enables high-resolution imaging of several different protein aggregates, such as aβ1-42, aβ1-42e22G, transthyretin V30M and human tau, in the Drosophila brain. aβ and tau aggregates could also be distinguished from each other because of distinct lco emission spectra. Furthermore, this protocol enables threedimensional brain mapping of amyloid distribution in whole-mount Drosophila brains. the use of p-Ftaa combined with other probes, antibodies and/or dyes will aid the rapid characterization of various amyloid deposits in the rapidly growing number of Drosophila models of neurodegenerative diseases.
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| 7. |
- Bremer, Johan, 1991, et al.
(author)
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Electric-Based Thermal Characterization of GaN Technologies Affected by Trapping Effects
- 2020
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In: IEEE Transactions on Electron Devices. - 1557-9646 .- 0018-9383. ; 67:5, s. 1952-1958
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Journal article (peer-reviewed)abstract
- This article presents an electric-based methodology for thermal characterization of semiconductor technologies. It is shown that for technologies such as gallium nitride (GaN) high electron mobility transistors, which exhibit several field induced electron trapping effects, the thermal characterization has to be performed under specific conditions. The electric field is limited to low levels to avoid activation of trap states. At the same time, the dissipated power needs to be high enough to change the operating temperature of the device. The method is demonstrated on a test structure implemented as a GaN resistor with large contact separation. It is used to evaluate the thermal properties of samples with different silicon carbide suppliers and buffer thickness.
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| 8. |
- Ek, C. Joakim, et al.
(author)
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Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia
- 2015
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In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 35:5, s. 818-827
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Journal article (peer-reviewed)abstract
- Insults to the developing brain often result in irreparable damage resulting in long-term deficits in motor and cognitive functions. The only treatment today for hypoxic-ischemic encephalopathy (HIE) in newborns is hypothermia, which has limited clinical benefit. We have studied changes to the blood-brain barriers (BBB) as well as regional cerebral blood flow (rCBF) in a neonatal model of HIE to further understand the underlying pathologic mechanisms. Nine-day old mice pups, brain roughly equivalent to the near-term human fetus, were subjected to hypoxia-ischemia. Hypoxia-ischemia increased BBB permeability to small and large molecules within hours after the insult, which normalized in the following days. The opening of the BBB was associated with changes to BBB protein expression whereas gene transcript levels were increased showing direct molecular damage to the BBB but also suggesting compensatory mechanisms. Brain pathology was closely related to reductions in rCBF during the hypoxia as well as the areas with compromised BBB showing that these are intimately linked. The transient opening of the BBB after the insult is likely to contribute to the pathology but at the same time provides an opportunity for therapeutics to better reach the infarcted areas in the brain.
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| 9. |
- Engberg, Anna E., 1982-
(author)
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Biomaterials and Hemocompatibility
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Biomaterials are commonly used in the medical clinic today; however, artificial materials can activate the cascade systems in the blood (complement-, coagulation-, contact- and fibrinolytic systems) as well as the platelets to various degrees. When an artificial surface comes in contact with blood, plasma proteins will be adsorbed to the surface within seconds. The composition of the layer of proteins differs between materials and is crucial for the hemocompatibility of the material.This thesis includes five projects.In Paper I the anticoagulants heparin and the thrombin inhibitor hirudin were evaluated in a whole blood model. Hirudin was found to be superior to low dose heparin since it did not affect the activation of the complement system nor the leukocytes. The most interesting observation was that expression of TF was seen on surface-attached monocytes in hirudin- treated blood but not heparin blood.In Paper II peptides from the streptococcal M-protein, which has affinity for the human complement inhibitor C4BP, were attached to a polymeric surface. When being exposed to blood the endogenous complement regulator was enriched at the surface of the material, via the M-peptides. With this new approach we created a self-regulatory surface, showing significant lowered material-induced complement activation.In Paper III apyrase, an enzyme which hydrolyzes nucleoside ATP and ADP, was immobilized on a polymer surface. Lower platelet activation and platelet-induced coagulation activation was seen for the apyrase-coated surface compared to control surfaces after exposure to whole human blood, due to the enzymes capability to degrade ADP released from activated platelets.In Paper IV and V we synthesized an array of polymeric materials which were characterized regarding physical-chemical properties, adsorption of plasma proteins, and hemocompatibility. The polymers showed widely heterogeneous protein adsorption. Furthermore, when the polymers were exposed to whole blood, two of the materials showed superior hemocompatibility (monitored as complement- and coagulation activation), compared to the reference poly(vinyl chloride).
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| 10. |
- Fagerberg, Linn, et al.
(author)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Journal article (peer-reviewed)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 11. |
- Ghandriz, Toheed, 1982, et al.
(author)
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Computationally Efficient Nonlinear One-and Two-Track Models for Multitrailer Road Vehicles
- 2020
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In: IEEE Access. - 2169-3536 .- 2169-3536. ; 8, s. 203854-203875
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Journal article (peer-reviewed)abstract
- This paper presents nonlinear mathematical models of one-and two-track multitrailer vehicles. We derive nonlinear equations of motion in the form of a system of implicit ordinary differential equations (ODEs) by using Lagrangian mechanics. The system of ODEs has the minimum number of states and equations that enables efficient computations yet maintains the most important nonlinear vehicle dynamic behavior and allows actuator coordination and energy consumption evaluation. As examples, we build different models of a 4-unit long combination vehicle, i.e., two-track 11-axle and single-track 6-axle nonlinear models as well as a linear single-track 6-axle model. We compare the performance of these models to experimental data of different driving maneuvers. The nonlinear single-track model demonstrates close dynamic behavior to the experiment, which makes it an efficient alternative to the two-track model. The vehicle equations can be generated automatically by using the code provided in this paper and subsequently used for conducting frequency analysis, evaluating energy consumption, deriving performance measures from simulations, and facilitating optimal control applications that involve combined steering, braking and propulsion control.
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| 12. |
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| 13. |
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| 14. |
- Ghandriz, Toheed, 1982, et al.
(author)
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Real-time Predictive Energy Management of Hybrid Electric Heavy Vehicles by Sequential Programming
- 2021
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In: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 70:5, s. 4113-4128
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Journal article (peer-reviewed)abstract
- With the objective of reducing fuel consumption, this paper presents real-time predictive energy management of hybrid electric heavy vehicles. We propose an optimal control strategy that determines the power split between different vehicle power sources and brakes. Based on the model predictive control (MPC) and sequential programming, the optimal trajectories of the vehicle velocity and battery state of charge are found for upcoming horizons with a length of 5-20 km. Then, acceleration and brake pedal positions together with the battery usage are regulated to follow the requested speed and state of charge that is verified using a vehicle plant model. The main contribution of this paper is the development of a sequential linear program for predictive energy management that is faster and simpler than sequential quadratic programming in tested solvers and gives trajectories that are very close to the best trajectories found by nonlinear programming. The performance of the method is also compared to two different sequential quadratic programs.
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| 15. |
- Ghandriz, Toheed, 1982, et al.
(author)
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Trajectory-Following and Off-Tracking Minimization of Long Combination Vehicles: A Comparison Between Nonlinear and Linear Model Predictive Control
- 2024
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In: Vehicle System Dynamics. - : Informa UK Limited. - 1744-5159 .- 0042-3114. ; 62:2, s. 277-310
-
Journal article (peer-reviewed)abstract
- In this paper, we compared the linear and nonlinear motion prediction models of a long combination vehicle (LCV). We designed a nonlinear model predictive control (NMPC) for trajectory-following and off-tracking minimisation of the LCV. The used prediction model allowed coupled longitudinal and lateral dynamics together with the possibility of a combined steering, propulsion and braking control of those vehicles in long prediction horizons and in all ranges of forward velocity. For LCVs where the vehicle model is highly nonlinear, we showed that the control actions calculated by a linear time-varying model predictive control (LTV-MPC) are relatively close to those obtained by the NMPC if the guess linearisation trajectory is sufficiently close to the nonlinear solution, in contrast to linearising for specific operating conditions that limit the generality of the designed function. We discussed how those guess trajectories can be obtained allowing off-line fixed time-varying model linearisation that is beneficial for real-time implementation of MPC in LCVs with long prediction horizons. The long prediction horizons are necessary for motion planning and trajectory-following of LCVs to maintain stability and tracking quality, e.g. by optimally reducing the speed prior to reaching a curve, and by generating control actions within the actuators limits.
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| 16. |
- Goodwin, Christopher M., 1989-, et al.
(author)
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Operando Probing of the Surface Chemistry During the Haber-Bosch Process
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 282-286
-
Journal article (peer-reviewed)abstract
- The Haber-Bosch process produces NH3 from N2 and H21,2, typically with Fe and Ru3. HB has been proposed as the most important scientific invention in the 20th century4. The chemical state during reaction has been proposed as oxides5, nitrides2, metallic, or surface nitride6. The proposed rate-limiting step has been the dissociation of N27–9, reaction of adsorbed nitrogen10, or desorption of NH311. Due to the vacuum requirement for surface-sensitive techniques, studies at reaction conditions are limited to theory computations12–14. We determined the surface composition, during NH3 production, at pressures up to 1 bar and temperatures as high as 723 K on flat, stepped Fe, and stepped Ru single crystal surfaces using operando X-ray Photoelectron Spectroscopy15. We found that all surfaces remain metallic. On Fe only a small amount of adsorbed N remains, yet Ru’s surface is almost adsorbate free. At 523 K, high amines (NHx) coverages appear on the stepped Fe surface. The results show that the rate-limiting step on Ru is always N2 dissociation. Still, on Fe the hydrogenation step involving adsorbed N atoms is essential for the total rate, as predicted by theory13. If the temperature is lowered on Fe, the rate-limiting steps switch and become surface species’ hydrogenation.
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| 17. |
- Grut, Viktor, et al.
(author)
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Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis
- 2024
-
In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 147:1, s. 177-185
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Journal article (peer-reviewed)abstract
- Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.
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| 18. |
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| 19. |
- Hlal, Fatima, 1989, et al.
(author)
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Life Cycle Cost and Life Cycle Assessment of Composite Bridge with Flat and Corrugated Webs
- 2023
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In: ce/papers. ; 6, s. 574-579
-
Journal article (peer-reviewed)abstract
- To satisfy the sustainability criteria, a bridge design must be economically viable during its entire service life with a minimal impact on the environment. While stainless steel is known for its excellent life cycle performance, its high cost prevents it from being used in bridges to a larger extent. This study evaluates a new design solution that takes advantage of using corrugated web in bridge girders to overcome this issue. Three design concepts are evaluated for a three-span case-study bridge. These include a bridge with carbon steel flat web, stainless steel flat web, and stainless-steel corrugated web girders. Each design is optimized using a genetic algorithm. The three optimal solutions are then evaluated in terms of investment costs, life cycle costs (LCC) and life cycle impact. The results show that the investment costs in a flat web girder bridge increase by 27% when stainless steel is used instead of C-Mn (carbon) steel. However, this increase is only 10% when corrugated web girders are used. On the other hand, the LCC savings increase from 6% to 18% for corrugated web girders. Finally, the use of corrugated web in stainless steel leads to a reduction in the climate impacts of up to 32% compared to carbon steel for the studied bridge.
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| 20. |
- Holmgren, Klas, 1989-
(author)
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Permanent stoma after anterior resection for rectal cancer : prevalence and mechanisms
- 2019
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Doctoral thesis (other academic/artistic)abstract
- While sphincter-saving surgery constitutes standard treatment for rectal cancer, anterior resection still harbours a significant risk of a permanent stoma in the long run. Although anastomotic leakage plays a major role in this surgical dilemma, the exact mechanisms are not known, while surveys indicate a stoma-free outcome is essential for a majority of patients. To address this issue, the overall aim of the present thesis was to investigate the permanent stoma prevalence in patients undergoing anterior resection for rectal cancer in Sweden, and to identify plausible mechanisms that impede prospects of a stoma-free outcome.In a population-based cohort, chart review of patients who had anterior resection for rectal cancer in the Northern healthcare region in Sweden between 2007 and 2013 showed that 75 out of 316 (24%) patients ended up with a permanent stoma. Of 274 patients (87%) primarily defunctioned with a stoma, 229 underwent stoma closure, 21 (9%) of whom suffered major complications that required return to theatre or worse. A permanent stoma was shown to be more common among patients with anastomotic leakage and an advanced tumour stage.A registry-based method to estimate nationwide stoma outcome after anterior resection for rectal cancer was developed, using data from the Swedish Colorectal Cancer Registry and the National Patient Registry. With a chart-reviewed cohort as reference, stoma outcome was assessed with a positive predictive value of 85.1%, and a negative predictive value of 100.0%. In patients operated in Sweden between 2007 and 2013, the registry-based method determined that 942 out of 4768 (19.8%) had a permanent stoma, while stoma rates varied substantially between different healthcare regions.In a 1:1 matched case-control study of 82 patients who had curative resection for non-disseminated colorectal cancer, a subgroup analysis of 34 patients with rectal cancer displayed biomarker aberrations in serum measured preoperatively in those with anastomotic leakage. Compared to complication-free controls, 15 proteins related to inflammation were elevated, of which two (C-X-C motif chemokine 6, and C-C motif chemokine 11) remained significant after adjustment for multiple testing.Based on a cohort of 4529 patients who had anterior resection, tumour height served as a proxy to determine the extent of mesorectal excision, while long-term stoma outcome was classified using a previously validated registry-based method. Defunctioning stomas significantly decreased chances of a stoma-free outcome, especially in patients undergoing partial mesorectal excision; for these patients, faecal diversion was also least beneficial in terms of reducing anastomotic leakage.In conclusion, every fifth patient undergoing anterior resection for rectal cancer in Sweden eventually ends up with a permanent stoma. Although construction of a defunctioning stoma decreases the risk of symptomatic anastomotic leakage, subsequent takedown surgery carries a substantial risk of major complications, while chances of a long-term stoma-free outcome become significantly reduced. To facilitate selective use of faecal diversion, novel markers to identify high-risk anastomoses prior to surgery have been identified, but require validation in larger prospective settings. Anterior resection without a defunctioning stoma should be considered in appropriately informed patients for whom a stoma-free outcome is of importance. In particular, this holds true for patients eligible for partial mesorectal excision, where anastomotic dehiscence is less frequent and the advantageous effects of a defunctioning stoma are limited.
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| 21. |
- Ingvarsson, Jens, et al.
(author)
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Rubella virus seropositivity after infection or vaccination as a risk factor for multiple sclerosis
- 2024
-
In: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331.
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Journal article (peer-reviewed)abstract
- Background: Multiple sclerosis (MS) is a demyelinating disease affecting millions of people worldwide. Hereditary susceptibility and environmental factors contribute to disease risk. Infection with Epstein–Barr virus (EBV) and human herpesvirus 6A (HHV-6A) have previously been associated with MS risk. Other neurotropic viruses, such as rubella virus (RV), are possible candidates in MS aetiopathogenesis, but previous results are limited and conflicting.Methods: In this nested case–control study of biobank samples in a Swedish cohort, we analysed the serological response towards RV before the clinical onset of MS with a bead-based multiplex assay in subjects vaccinated and unvaccinated towards RV. The association between RV seropositivity and MS risk was analysed with conditional logistic regression.Results: Seropositivity towards RV was associated with an increased risk of MS for unvaccinated subjects, even when adjusting for plausible confounders including EBV, HHV-6A, cytomegalovirus and vitamin D (adjusted odds ratio [AOR] = 4.0, 95% confidence interval [CI] 1.8–8.8). Cases also had stronger antibody reactivity towards rubella than controls, which was not seen for other neurotropic viruses such as herpes simplex or varicella zoster. Furthermore, we observed an association between RV seropositivity and MS in vaccinated subjects. However, this association was not significant when adjusting for the aforementioned confounders (AOR = 1.7, 95% CI 1.0–2.9).Conclusions: To our knowledge, these are the first reported associations between early RV seropositivity and later MS development. This suggests a broadening of the virus hypothesis in MS aetiology, where molecular mimicry between rubella epitopes and human central nervous system molecules could be an attractive possible mechanism.
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| 22. |
- Jons, Daniel, 1974, et al.
(author)
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Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis
- 2022
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In: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 9:6, s. 882-887
-
Journal article (peer-reviewed)abstract
- Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case-control study, blood samples from 519 presymptomatic persons (age range 4-39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0-5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5-10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.
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| 23. |
- Jons, Daniel, 1974, et al.
(author)
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Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
- 2023
-
In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 1468-330X .- 0022-3050. ; 95
-
Journal article (peer-reviewed)abstract
- Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
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| 24. |
- Koh, Ara, et al.
(author)
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Microbial Imidazole Propionate Affects Responses to Metformin through p38 gamma-Dependent Inhibitory AMPK Phosphorylation
- 2020
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 32:4
-
Journal article (peer-reviewed)abstract
- Metformin is the first-line therapy for type 2 diabetes, but there are large inter-individual variations in responses to this drug. Its mechanism of action is not fully understood, but activation of AMP-activated protein kinase (AMPK) and changes in the gut microbiota appear to be important. The inhibitory role of microbial metabolites on metformin action has not previously been investigated. Here, we show that concentrations of the microbial metabolite imidazole propionate are higher in subjects with type 2 diabetes taking metformin who have high blood glucose. We also show that metformin-induced glucose lowering is not observed in mice pretreated with imidazole propionate. Furthermore, we demonstrate that imidazole propionate inhibits AMPK activity by inducing inhibitory AMPK phosphorylation, which is dependent on imidazole propionate-induced basal Akt activation. Finally, we identify imidazole propionate-activated p38 gamma as a novel kinase for Akt and demonstrate that p38 gamma kinase activity mediates the inhibitory action of imidazole propionate on metformin.
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| 25. |
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