| 1. |
- Rosenqvist, L., et al.
(författare)
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3D Modeling of Geomagnetically Induced Currents in Sweden-Validation and Extreme Event Analysis
- 2022
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Rosenqvist and Hall (2019), developed a proof-of-concept modeling capability that incorporates a detailed 3D structure of Earth's electrical conductivity in a geomagnetically induced current estimation procedure (GIC-SMAP). The model was verified based on GIC measurements in northern Sweden. The study showed that southern Sweden is exposed to stronger electric fields due to a combined effect of low crustal conductivity and the influence of the surrounding coast. This study aims at further verifying the model in this region. GIC measurements on a power line at the west coast of southern Sweden are utilized. The location of the transmission line was selected to include coast effects at the ocean-land interface to investigate the importance of using 3D induction modeling methods. The model is used to quantify the hazard of severe GICs in this particular transmission line by using historic recordings of strong geomagnetic disturbances. To quantify a worst-case scenario GICs are calculated from modeled magnetic disturbances by the Space Weather Modeling Framework based on estimates for an idealized extreme interplanetary coronal mass ejection. The observed and estimated GIC based on the 3D GIC-SMAP procedure in the transmission line in southern Sweden are in good agreement. In contrast, 1D methods underestimate GICs by about 50%. The estimated GICs in the studied transmission line exceed 100 A for one of 14 historical geomagnetic storm intervals. The peak GIC during the sudden impulse phase of a "perfect" storm exceeds 300 A but depends on the locality of the station as the interplanetary magnetic cloud hits Earth.
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| 2. |
- Rosenqvist, L., et al.
(författare)
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3D Modeling of Geomagnetically Induced Currents in Sweden—Validation and Extreme Event Analysis
- 2022
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Ingår i: Space Weather. - : John Wiley & Sons. - 1542-7390. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Rosenqvist and Hall (2019), https://agupubs.onlinelibrary.wiley.com/doi/abs/10.1029/2018SW002084 developed a proof-of-concept modeling capability that incorporates a detailed 3D structure of Earth's electrical conductivity in a geomagnetically induced current estimation procedure (GIC-SMAP). The model was verified based on GIC measurements in northern Sweden. The study showed that southern Sweden is exposed to stronger electric fields due to a combined effect of low crustal conductivity and the influence of the surrounding coast. This study aims at further verifying the model in this region. GIC measurements on a power line at the west coast of southern Sweden are utilized. The location of the transmission line was selected to include coast effects at the ocean-land interface to investigate the importance of using 3D induction modeling methods. The model is used to quantify the hazard of severe GICs in this particular transmission line by using historic recordings of strong geomagnetic disturbances. To quantify a worst-case scenario GICs are calculated from modeled magnetic disturbances by the Space Weather Modeling Framework based on estimates for an idealized extreme interplanetary coronal mass ejection. The observed and estimated GIC based on the 3D GIC-SMAP procedure in the transmission line in southern Sweden are in good agreement. In contrast, 1D methods underestimate GICs by about 50%. The estimated GICs in the studied transmission line exceed 100 A for one of 14 historical geomagnetic storm intervals. The peak GIC during the sudden impulse phase of a “perfect” storm exceeds 300 A but depends on the locality of the station as the interplanetary magnetic cloud hits Earth.
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| 3. |
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| 4. |
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| 5. |
- Anwer, Danish M., et al.
(författare)
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A comparison of machine learning approaches for the quantification of microglial cells in the brain of mice, rats and non-human primates
- 2023
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Ingår i: PLoS ONE. - 1932-6203. ; 18:5 MAY
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Tidskriftsartikel (refereegranskat)abstract
- Microglial cells are brain-specific macrophages that swiftly react to disruptive events in the brain. Microglial activation leads to specific modifications, including proliferation, morphological changes, migration to the site of insult, and changes in gene expression profiles. A change in inflammatory status has been linked to many neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. For this reason, the investigation and quantification of microglial cells is essential for better understanding their role in disease progression as well as for evaluating the cytocompatibility of novel therapeutic approaches for such conditions. In the following study we implemented a machine learning-based approach for the fast and automatized quantification of microglial cells; this tool was compared with manual quantification (ground truth), and with alternative free-ware such as the threshold-based ImageJ and the machine learning-based Ilastik. We first trained the algorithms on brain tissue obtained from rats and non-human primate immunohistochemically labelled for microglia. Subsequently we validated the accuracy of the trained algorithms in a preclinical rodent model of Parkinson's disease and demonstrated the robustness of the algorithms on tissue obtained from mice, as well as from images provided by three collaborating laboratories. Our results indicate that machine learning algorithms can detect and quantify microglial cells in all the three mammalian species in a precise manner, equipotent to the one observed following manual counting. Using this tool, we were able to detect and quantify small changes between the hemispheres, suggesting the power and reliability of the algorithm. Such a tool will be very useful for investigation of microglial response in disease development, as well as in the investigation of compatible novel therapeutics targeting the brain. As all network weights and labelled training data are made available, together with our step-by-step user guide, we anticipate that many laboratories will implement machine learning-based quantification of microglial cells in their research.
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| 6. |
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| 7. |
- Brynskog, Erik, 1989, et al.
(författare)
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Predicting pelvis geometry using a morphometric model with overall anthropometric variables
- 2021
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Pelvic fractures have been identified as the second most common AIS2+ injury in motor vehicle crashes, with the highest early mortality rate compared to other orthopaedic injuries. Further, the risk is associated with occupant sex, age, stature and body mass index (BMI). In this study, clinical pelvic CT scans from 132 adults (75 females, 57 males) were extracted from a patient database. The population shape variance in pelvis bone geometry was studied by Sparse Principal Component Analysis (SPCA) and a morphometric model was developed by multi- variate linear regression using overall anthropometric variables (sex, age, stature, BMI). In the analysis, SPCA identified 15 principal components (PCs) describing 83.6% of the shape variations. Eight of these were signifi- cantly captured (α < 0.05) by the morphometric model, which predicted 29% of the total variance in pelvis geometry. The overall anthropometric variables were significantly related to geometrical features primarily in the inferior-anterior regions while being unable to significantly capture local sacrum features, shape and position of ASIS and lateral tilt of the iliac wings. In conclusion, a new detailed morphometric model of the pelvis bone demonstrated that overall anthropometric variables account for only 29% of the variance in pelvis geometry. Furthermore, variations in the superior-anterior region of the pelvis, with which the lap belt is intended to interact, were not captured. Depending on the scenario, shape variations not captured by overall anthropometry could have important implications for injury prediction in traffic safety analysis.
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| 8. |
- Cyron, Thomas
(författare)
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How organizations incorporate insights from stakeholder communication : The role of media and modal affordances
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organizations are increasingly opening up to external voices that might carry new insights and help organizations to find their place in society. But the context through which organizations communicate with their stakeholders shapes how communication unfolds. Traditionally, organizations communicated with their stakeholders through shareholder letters, town hall meetings, or printed advertisements. Nowadays, cyberspace has opened up communication in multiple ways. It affords fast and boundless two-way communication between organizations and stakeholders and among stakeholders, that can be both a blessing and a curse. In any case, changes in the communication landscape have affected all types of organizations—large corporations, small and medium-sized enterprises, and newly started ventures.My research connects to ongoing discussions on how new media have shaped the landscape of organizations. Specifically, I explore how organizations incorporate insights from stakeholder communication from a practice-based view. This view allows me to magnify and understand better how the communication context shapes the interaction. My empirical research focuses on stakeholder communication in a single-case study of the world’s largest miniature model railway exhibition and three new venture ideation cases. I employ a mix of qualitative research methods, including digital data collection techniques.A bricolage of the four papers included in this dissertation frames the insights under the assumption that communication constitutes organization. It allows me to conceptualize the incorporation of new insights from stakeholder communication as a co-authoring process. Specifically, I show that modes provide the meaning-making resources through which humans communicate organizations into being. Media act as vessels of modes and shape how stakeholders can interact with—and co-author—the modes.My future research agenda focuses on two aspects. First, I suggest following more closely how new narratives that stakeholders offer during the co-authoring process subsequently travel through an organization. This question is particularly relevant in larger corporations where the newly proposed narratives have to travel more considerable distances between stakeholder communication practices and decision-making practices. Second, I suggest investigating stakeholder communication from a design perspective, that is, a study of the heuristics that managers and entrepreneurs employ before engaging in stakeholder communication.
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| 9. |
- Davidsson, Marcus, et al.
(författare)
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A comparison of AAV-vector production methods for gene therapy and preclinical assessment
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Adeno Associated Virus (AAV)-mediated gene expression in the brain is widely applied in the preclinical setting to investigate the therapeutic potential of specific molecular targets, characterize various cellular functions, and model central nervous system (CNS) diseases. In therapeutic applications in the clinical setting, gene therapy offers several advantages over traditional pharmacological based therapies, including the ability to directly manipulate disease mechanisms, selectively target disease-afflicted regions, and achieve long-term therapeutic protein expression in the absence of repeated administration of pharmacological agents. Next to the gold-standard iodixanol-based AAV vector production, we recently published a protocol for AAV production based on chloroform-precipitation, which allows for fast in-house production of small quantities of AAV vector without the need for specialized equipment. To validate our recent protocol, we present here a direct side-by-side comparison between vectors produced with either method in a series of in vitro and in vivo assays with a focus on transgene expression, cell loss, and neuroinflammatory responses in the brain. We do not find differences in transduction efficiency nor in any other parameter in our in vivo and in vitro panel of assessment. These results suggest that our novel protocol enables most standardly equipped laboratories to produce small batches of high quality and high titer AAV vectors for their experimental needs.
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| 10. |
- Dods, Robert, 1989, et al.
(författare)
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Ultrafast structural changes within a photosynthetic reaction centre.
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7841, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography1 using an X-ray free-electron laser2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions.
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| 11. |
- Glombik, D, 1988-, et al.
(författare)
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Morbidity following lymphadenectomy for penile cancer in a Swedish national cohort
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S1024-S1024
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: To assess the rate of postoperative infectious and thromboembolic complications associated with inguinal (ILND) and pelvic (PLND) lymph node dissection in penile cancer and identify clinical and pathological predictors for the development of these complications.Materials & Methods: A total of 364 men subjected to ILND with or without PLND for squamous cell carcinoma of the penis between 2000 and 2012 were identified through the Swedish National Penile Cancer Register. Each patient was matched based on age and county of residence with 6 penile cancer-free men. The Swedish cancer and population registers were used to retrieve information about treatment and hospitalization for infections of the lower limbs, groins, genitalia, trunk and various septic conditions as well as thromboembolic events based on ICD-10 codes for each event. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazard models with multiple imputation to assess the effects of different variables. The net hazard rates of outcomes were estimated using a flexible parametric model.Results: The risk to suffer from infectious events remained increased up to 6 years postoperatively in penile cancer patients who underwent ILND in comparison to the matched controls. Palpable nodal disease was the only predictor of increased risk of infectious complications. The risk tends to increase with the cN stage, with a HR of 1.65 (95% CI 0.98-2.77) for cN1, 1.93 (95% CI 1.14-3.29) for cN2 and 2.62 (95% CI 1.41-4.88) for cN3 disease. Risks for the first, third and sixth postoperative year were assessed with HRs of 8.87 (95% CI 5.36-14.66), 4.20 (95% CI 2.77-6.35) and 1.83 (95% CI 0.96-3.46) respectively. The increased risk of thromboembolic events persisted up to 3 years postoperatively, HRs for the first and third postoperative year were 13.51 (95% CI 6.53-27.93) respectively 2.12 (95% CI 1.07-4.20). The results correspond well with the over-prescription of anticoagulants observed during this period. An association with bulky disease was observed, with a HR of 3.81 (95% CI 1.10-13.17) for cN3 stage. PLND did not add any excessive risks for either infectious or thromboembolic events.Conclusions: Based on data from nationwide registers of high quality and completeness, we could assess postoperative morbidity after lymphadenectomy for penile cancer with follow-up length ranging up to 12 years. Patients with palpable nodal disease are at increased risk of infectious complications up to 6 years postoperatively. The risk of thromboembolic complications was increased during first 3 postoperative years. Patients and care givers need to be aware of the increased risk of these complications and preventive measures should be considere
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| 12. |
- Gubinelli, F., et al.
(författare)
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Characterisation of functional deficits induced by AAV overexpression of alpha-synuclein in rats
- 2023
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Ingår i: Current Research in Neurobiology. - : Elsevier BV. - 2665-945X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the last decades different preclinical animal models of Parkinson's disease (PD) have been generated, aiming to mimic the progressive neuronal loss of midbrain dopaminergic (DA) cells as well as motor and non-motor impairment. Among all the available models, AAV-based models of human alpha-synuclein (h-aSYN) overexpression are promising tools for investigation of disease progression and therapeutic interventions. Objectives: The goal with this work was to characterise the impairment in motor and non-motor domains following nigrostriatal overexpression of h-aSYN and correlate the behavioural deficits with histological assessment of associated pathology. Methods: Intranigral injection of an AAV9 expressing h-aSYN was compared with untreated animals, 6-OHDA and AAV9 expressing either no transgene or GFP. The animals were assessed on a series of simple and complex behavioural tasks probing motor and non-motor domains. Post-mortem neuropathology was analysed using immunohistochemical methods. Results: Overexpression of h-aSYN led to progressive degeneration of DA neurons of the SN and axonal terminals in the striatum (STR). We observed extensive nigral and striatal pathology, resembling that of human PD brain, as well as the development of stable progressive deficit in simple motor tasks and in non-motor domains such as deficits in motivation and lateralised neglect. Conclusions: In the present work we characterized a rat model of PD that closely resembles human PD pathology at the histological and behavioural level. The correlation of cell loss with behavioural performance enables the selection of rats which can be used in neuroprotective or neurorestorative therapies.
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| 13. |
- Gubinelli, F., et al.
(författare)
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Lateralized deficits after unilateral AAV-vector based overexpression of alpha-synuclein in the midbrain of rats on drug-free behavioral tests
- 2022
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 429
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preclinical rodent models of Parkinson's aim to recapitulate some of the hallmarks of the disease as it presents in humans, including the progressive neuronal loss of dopaminergic neurons in the midbrain as well as the development of a behavioral phenotype. AAV vector-based models of alpha-synuclein overexpression are a promising tool to achieve such animal models with high face and predictive validity. Objective: We have developed a preclinical rodent model of Parkinson's disease using an AAV-vector based overexpression of human alpha-synuclein. In the present work we characterize this model on a behavioral and histopathological level. Methods: We use a AAV9 vector for transgene delivery to overexpress human alpha-synuclein under a CBA promoter. We compare the behavioral and histopathological changes to a AAV vector control group where the transgene was omitted and to that of a 6-OHDA lesion control. We assessed the behavioral performance of these three groups on a series of tests (Cylinder, Stepping, Corridor) at baseline and up to 22 weeks post-injection at which point we performed electrochemical recordings of dopamine kinetics. Results: The overexpression of human alpha-synuclein led to the progressive manifestation of behavioral deficits on all three behavioral tests. This was accompanied with impaired dopamine release and reuptake kinetics as demonstrated by electrochemical detection methods. Histopathological quantifications corroborated the findings that we induced a moderate cell loss with remaining cells displaying pathological markers which are abundant in the brains of human PD patients. Conclusions: In the present work we developed a characterized a rat model of PD that closely mimics human disease development and pathology. Such model will be of great use for investigation of disease mechanisms and early therapeutic interventions.
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| 14. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 15. |
- Negrini, Matilde, et al.
(författare)
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Sequential or Simultaneous Injection of Preformed Fibrils and AAV Overexpression of Alpha-Synuclein Are Equipotent in Producing Relevant Pathology and Behavioral Deficits
- 2022
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 12:4, s. 1133-1153
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preclinical rodent models for Parkinson's disease (PD) based on viral human alpha-synuclein (h-αSyn) overexpression recapitulate some of the pathological hallmarks as it presents in humans, such as progressive cell loss and additional synucleinopathy in cortical and subcortical structures. Recent studies have combined viral vector-based overexpression of human wild-type αSyn with the sequential or simultaneous inoculation of preformed fibrils (PFFs) derived from human αSyn. Objective: The goal of the study was to investigate whether sequential or combined delivery of the AAV vector and the PFFs are equipotent in inducing stable neurodegeneration and behavioral deficits. Methods: Here we compare between four experimental paradigms (PFFs only, AAV-h-αSyn only, AAV-h-αSyn with simultaneous PFFs, and AAV-h-αSyn with sequential PFFs) and their respective GFP control groups. Results: We observed reduction of TH expression and loss of neurons in the midbrain in all AAV (h-αSyn or GFP) injected groups, with or without additional PFFs inoculation. The overexpression of either h-αSyn or GFP alone induced motor deficits and dysfunctional dopamine release/reuptake in electrochemical recordings in the ipsilateral striatum. However, we observed a substantial formation of insoluble h-αSyn aggregates and inflammatory response only when h-αSyn and PFFs were combined. Moreover, the presence of h-αSyn induced higher axonal pathology compared to control groups. Conclusion: Simultaneous AAV and PFFs injections are equipotent in the presented experimental setup in inducing histopathological and behavioral changes. This model provides new and interesting possibilities for characterizing PD pathology in preclinical models and means to assess future therapeutic interventions.
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| 16. |
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| 17. |
- Wendin, Karin, et al.
(författare)
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Introducing mealworm as an ingredient in crisps and pâtés – sensory characterization and consumer liking
- 2021
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Ingår i: Future Foods. - : Elsevier B.V.. - 2666-8335. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate sensory perception and consumers’ attitude and liking of products with different textures, crisps and pâtés, with added mealworm ingredient in different amounts. By addition of mealworm (Tenebrio molitor L.) in the crisps, the brittleness increased. However, an increase in mealworm also increased the darkness. Adding mealworms to pâté reduced the odour and flavour of vegetable and increased the flavour of cinnamon and pepper as well as the oily texture. There was no significant difference in total liking between 10 and 30% addition of mealworm, nor between 0 and 10% addition, in any of the two products. The crisps received higher liking score than the pâtés. Thus, there is also a much higher probability that a customer would buy insect crisps than insect pâté. Environmental sustainability and sensory properties were shown to be the main reasons for buying foods with added insect ingredients. © 2021 The Authors
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