| 1. |
- Escartin, C., et al.
(författare)
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Reactive astrocyte nomenclature, definitions, and future directions
- 2021
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 24, s. 312-325
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good-bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.
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| 2. |
- Andreasson, K. I., et al.
(författare)
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Targeting innate immunity for neurodegenerative disorders of the central nervous system
- 2016
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; , s. 653-693
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7–9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. (Figure presented.) Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7–9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. © 2016 International Society for Neurochemistry
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| 3. |
- Culina, Antica, et al.
(författare)
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Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
- 2021
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Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
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Tidskriftsartikel (refereegranskat)abstract
- The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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| 4. |
- Stokowska, Anna, et al.
(författare)
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Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity
- 2023
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:10
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Tidskriftsartikel (refereegranskat)abstract
- Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.
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| 5. |
- Vardjan, N., et al.
(författare)
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IFN-gamma-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments
- 2012
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 9:Article Number: 144
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Tidskriftsartikel (refereegranskat)abstract
- Background: In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-gamma (IFN-gamma) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs. Methods: The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-gamma activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor(546)-dextran labeling of late endosomes/lysosomes in IFN-gamma treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software. Results: Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-gamma induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor(546)-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-gamma-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-gamma- treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-gamma-induced increase in the mobility of MHC class II compartments is IF-dependent. Conclusions: Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.
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| 6. |
- Aswendt, M., et al.
(författare)
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Reactive astrocytes prevent maladaptive plasticity after ischemic stroke
- 2022
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Ingår i: Progress in Neurobiology. - : Elsevier BV. - 0301-0082. ; 209
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Tidskriftsartikel (refereegranskat)abstract
- Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after photothrombotic stroke in mice with attenuated reactive gliosis (GFAP–/–Vim–/–). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP–/–Vim–/– mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes modulate recovery-promoting plasticity responses after ischemic stroke. © 2021
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| 7. |
- Babes, Alexandru, et al.
(författare)
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Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1
- 2016
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Ingår i: The Journal of Neuroscience. - 0270-6474. ; 36:19, s. 5264-5278
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Tidskriftsartikel (refereegranskat)abstract
- Photosensitization, an exaggerated sensitivity to harmless light, occurs genetically in rare diseases, such as porphyrias, and in photodynamic therapy where short-term toxicity is intended. A common feature is the experience of pain from bright light. In human subjects, skin exposure to 405 nm light induced moderate pain, which was intensified by pretreatment with aminolevulinic acid. In heterologous expression systems and cultured sensory neurons, exposure to blue light activated TRPA1 and, to a lesser extent, TRPV1 channels in the absence of additional photosensitization. Pretreatment with aminolevulinic acid or with protoporphyrin IX dramatically increased the light sensitivity of both TRPA1 and TRPV1 via generation of reactive oxygen species. Artificial lipid bilayers equipped with purified human TRPA1 showed substantial single-channel activity only in the presence of protoporphyrin IX and blue light. Photosensitivity and photosensitization could be demonstrated in freshly isolated mouse tissues and led to TRP channel-dependent release of proinflammatory neuropeptides upon illumination. With antagonists in clinical development, these findings may help to alleviate pain during photodynamic therapy and also allow for disease modification in porphyria patients.
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| 8. |
- de Pablo, Yolanda, et al.
(författare)
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Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes
- 2019
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Vimentin (VIM) is an intermediate filament (nanofilament) protein expressed in multiple cell types, including astrocytes. Mice with VIM mutations of serine sites phosphorylated during mitosis (VIMSA/SA) show cytokinetic failure in fibroblasts and lens epithelial cells, chromosomal instability, facilitated cell senescence, and increased neuronal differentiation of neural progenitor cells. Here we report that in vitro immature VIMSA/SA astrocytes exhibit cytokinetic failure and contain vimentin accumulations that co-localize with mitochondria. This phenotype is transient and disappears with VIMSA/SA astrocyte maturation and expression of glial fibrillary acidic protein (GFAP); it is also alleviated by the inhibition of cell proliferation. To test the hypothesis that GFAP compensates for the effect of VIMSA/SA in astrocytes, we crossed the VIMSA/SA and GFAP(-/-) mice. Surprisingly, the fraction of VIMSA/SA immature astrocytes with abundant vimentin accumulations was reduced when on GFAP(-/-) background. This indicates that the disappearance of vimentin accumulations and cytokinetic failure in mature astrocyte cultures are independent of GFAP expression. Both VIMSA/SA and VIM(SA/SA)GFAP(-/-) astrocytes showed normal mitochondrial membrane potential and vulnerability to H2O2, oxygen/glucose deprivation, and chemical ischemia. Thus, mutation of mitotic phosphorylation sites in vimentin triggers formation of vimentin accumulations and cytokinetic failure in immature astrocytes without altering their vulnerability to oxidative stress.
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| 9. |
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| 10. |
- Liu, Z. W., et al.
(författare)
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Beneficial Effects of GFAP/Vimentin Reactive Astrocytes for Axonal Remodeling and Motor Behavioral Recovery in Mice after Stroke
- 2014
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Ingår i: Glia. - : Wiley. - 0894-1491. ; 62:12, s. 2022-2033
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Tidskriftsartikel (refereegranskat)abstract
- The functional role of reactive astrocytes after stroke is controversial. To elucidate whether reactive astrocytes contribute to neurological recovery, we compared behavioral outcome, axonal remodeling of the corticospinal tract (CST), and the spatio-temporal change of chondroitin sulfate proteoglycan (CSPG) expression between wild-type (WT) and glial fibrillary acidic protein/vimentin double knockout (GFAP(-/-)Vim(-/-)) mice subjected to Rose Bengal induced cerebral cortical photothrombotic stroke in the right forelimb motor area. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the CST axons. Compared with WT mice, the motor functional recovery and BDA-positive CST axonal length in the denervated side of the cervical gray matter were significantly reduced in GFAP(-/-)Vim(-/-) mice (n=10/group, P<0.01). Immunohistological data showed that in GFAP(-/-)Vim(-/-) mice, in which astrocytic reactivity is attenuated, CSPG expression was significantly increased in the lesion remote areas in both hemispheres, but decreased in the ischemic lesion boundary zone, compared with WT mice (n=12/group, P<0.001). Our data suggest that attenuated astrocytic reactivity impairs or delays neurological recovery by reducing CST axonal remodeling in the denervated spinal cord. Thus, manipulation of astrocytic reactivity post stroke may represent a therapeutic target for neurorestorative strategies. GLIA 2014;62:2022-2033 Post stroke, GFAP/Vimentin knockout mice with attenuated gliosis have reduced or slower neurological recovery and corticospinal remodeling, and increased chondroitin sulfate proteoglycan expression, suggesting that reactive astrocytes promote recovery.
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| 11. |
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| 12. |
- Matusova, Z., et al.
(författare)
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Reactive astrogliosis in the era of single-cell transcriptomics
- 2023
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Ingår i: Frontiers in Cellular Neuroscience. - 1662-5102. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrogliosis is a reaction of astrocytes to disturbed homeostasis in the central nervous system (CNS), accompanied by changes in astrocyte numbers, morphology, and function. Reactive astrocytes are important in the onset and progression of many neuropathologies, such as neurotrauma, stroke, and neurodegenerative diseases. Single-cell transcriptomics has revealed remarkable heterogeneity of reactive astrocytes, indicating their multifaceted functions in a whole spectrum of neuropathologies, with important temporal and spatial resolution, both in the brain and in the spinal cord. Interestingly, transcriptomic signatures of reactive astrocytes partially overlap between neurological diseases, suggesting shared and unique gene expression patterns in response to individual neuropathologies. In the era of single-cell transcriptomics, the number of new datasets steeply increases, and they often benefit from comparisons and integration with previously published work. Here, we provide an overview of reactive astrocyte populations defined by single-cell or single-nucleus transcriptomics across multiple neuropathologies, attempting to facilitate the search for relevant reference points and to improve the interpretability of new datasets containing cells with signatures of reactive astrocytes.
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| 13. |
- Pekny, Milos, 1965, et al.
(författare)
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Astrocytes - a central element in neurological diseases.
- 2016
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:3, s. 323-345
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Forskningsöversikt (refereegranskat)abstract
- The neurone-centred view of the past disregarded or downplayed the role of astroglia as a primary component in the pathogenesis of neurological diseases. As this concept is changing, so is also the perceived role of astrocytes in the healthy and diseased brain and spinal cord. We have started to unravel the different signalling mechanisms that trigger specific molecular, morphological and functional changes in reactive astrocytes that are critical for repairing tissue and maintaining function in CNS pathologies, such as neurotrauma, stroke, or neurodegenerative diseases. An increasing body of evidence shows that the effects of astrogliosis on the neural tissue and its functions are not uniform or stereotypic, but vary in a context-specific manner from astrogliosis being an adaptive beneficial response under some circumstances to a maladaptive and deleterious process in another context. There is a growing support for the concept of astrocytopathies in which the disruption of normal astrocyte functions, astrodegeneration or dysfunctional/maladaptive astrogliosis are the primary cause or the main factor in neurological dysfunction and disease. This review describes the multiple roles of astrocytes in the healthy CNS, discusses the diversity of astroglial responses in neurological disorders and argues that targeting astrocytes may represent an effective therapeutic strategy for Alexander disease, neurotrauma, stroke, epilepsy and Alzheimer’s disease as well as other neurodegenerative diseases.
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| 14. |
- Statsenko, Yauhen, et al.
(författare)
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Multimodal diagnostics in multiple sclerosis : predicting disability and conversion from relapsing-remitting to secondary progressive disease course - protocol for systematic review and meta-analysis
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:7
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The number of patients diagnosed with multiple sclerosis (MS) has increased significantly over the last decade. The challenge is to identify the transition from relapsing-remitting to secondary progressive MS. Since available methods to examine patients with MS are limited, both the diagnostics and prognostication of disease progression would benefit from the multimodal approach. The latter combines the evidence obtained from disparate radiologic modalities, neurophysiological evaluation, cognitive assessment and molecular diagnostics. In this systematic review we will analyse the advantages of multimodal studies in predicting the risk of conversion to secondary progressive MS.METHODS AND ANALYSIS: We will use peer-reviewed publications available in Web of Science, Medline/PubMed, Scopus, Embase and CINAHL databases. In vivo studies reporting the predictive value of diagnostic methods will be considered. Selected publications will be processed through Covidence software for automatic deduplication and blind screening. Two reviewers will use a predefined template to extract the data from eligible studies. We will analyse the performance metrics (1) for the classification models reflecting the risk of secondary progression: sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, positive and negative predictive values; (2) for the regression models forecasting disability scores: the ratio of mean absolute error to the range of values. Then, we will create ranking charts representing performance of the algorithms for calculating disability level and MS progression. Finally, we will compare the predictive power of radiological and radiomical correlates of clinical disability and cognitive impairment in patients with MS.ETHICS AND DISSEMINATION: The study does not require ethical approval because we will analyse publicly available literature. The project results will be published in a peer-review journal and presented at scientific conferences.PROSPERO REGISTRATION NUMBER: CRD42022354179.
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| 15. |
- Struwe, Weston B, et al.
(författare)
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The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets.
- 2016
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 26:9, s. 907-910
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Tidskriftsartikel (refereegranskat)abstract
- Theminimum information required for a glycomics experiment (MIRAGE) project was established in 2011 to provide guidelines to aid in data reporting from all types of experiments in glycomics research including mass spectrometry (MS), liquid chromatography, glycan arrays, data handling and sample preparation. MIRAGE is a concerted effort of the wider glycomics community that considers the adaptation of reporting guidelines as an important step towards critical evaluation and dissemination of datasets as well as broadening of experimental techniques worldwide. The MIRAGE Commission published reporting guidelines for MS data and here we outline guidelines for sample preparation. The sample preparation guidelines include all aspects of sample generation, purification and modification from biological and/or synthetic carbohydrate material. The application of MIRAGE sample preparation guidelines will lead to improved recording of experimental protocols and reporting of understandable and reproducible glycomics datasets.
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| 16. |
- Walton, Esther, et al.
(författare)
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Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa : A Coordinated Analysis by the ENIGMA Eating Disorders Working Group
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 92:9, s. 730-738
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and de-pendencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data.METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251).RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of un-dernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients.CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.
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| 17. |
- Andersson, Daniel, 1979, et al.
(författare)
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Plasticity Response in the Contralesional Hemisphere after Subtle Neurotrauma: Gene Expression Profiling after Partial Deafferentation of the Hippocampus
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Neurotrauma or focal brain ischemia are known to trigger molecular and structural responses in the uninjured hemisphere. These responses may have implications for tissue repair processes as well as for the recovery of function. To determine whether the plasticity response in the uninjured hemisphere occurs even after a subtle trauma, we subjected mice to a partial unilateral deafferentation of the hippocampus induced by stereotactically performed entorhinal cortex lesion (ECL). The expression of selected genes was assessed by quantitative real-time PCR in the hippocampal tissue at the injured side and the contralesional side at day 4 and 14 after injury. We observed that expression of genes coding for synaptotagmin 1, ezrin, thrombospondin 4, and C1q proteins, that have all been implicated in the synapse formation, re-arrangement and plasticity, were upregulated both in the injured and the contralesional hippocampus, implying a plasticity response in the uninjured hemisphere. Several of the genes, the expression of which was altered in response to ECL, are known to be expressed in astrocytes. To test whether astrocyte activation plays a role in the observed plasticity response to ECL, we took advantage of mice deficient in two intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-) Vim(-/-)) and exhibiting attenuated astrocyte activation and reactive gliosis. The absence of GFAP and vimentin reduced the ECL-induced upregulation of thrombospondin 4, indicating that this response to ECL depends on astrocyte activation and reactive gliosis. We conclude that even a very limited focal neurotrauma triggers a distinct response at the contralesional side, which at least to some extent depends on astrocyte activation.
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| 18. |
- Antić, Aleksandar, et al.
(författare)
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Loess and geotourism potential of the Braničevo District (NE Serbia) : From overexploitation to paleoclimate interpretation
- 2023
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Ingår i: Open Geosciences. - 2391-5447. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The use of loess as a resource for paleoclimatic research is quite well established. In Serbia, a significant number of loess sequences have been preserved in old brickyards. The results of the previously conducted research indicate extremely valuable data that enable a better understanding of the mid- to late Pleistocene climatic evolution in this part of Europe, as well as human dispersal from Africa to Europe via the so-called Danubian migration corridor. The aim of this study is to evaluate the geotourism potentials of the loess profiles in Pożarevac (northeastern Serbia). The goal is to determine their geotourism potential for paleoclimate interpretation. The Modified Geoheritage Assessment Model method has identified exceptional geotourism potentials that can be implemented in the tourism market. Paleoclimatic data can serve as indicators for the development of scientific visitor centers for the promotion and popularization of paleoclimate science and museums, which will affirm sustainable socio-economic development through multidisciplinary interpretation. By combining geological, paleoclimatic, archaeological, biological, and other values that reveal natural and anthropogenic events from the distant past, it is possible to create a very competitive geotourism destination, whose sustainability can be passed on to future generations.
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| 19. |
- Björnberg, Jakob E., 1983, et al.
(författare)
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The interchange process with reversals on the complete graph
- 2019
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Ingår i: Electronic Journal of Probability. - : Institute of Mathematical Statistics. - 1083-6489. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- We consider an extension of the interchange process on the complete graph, in which a fraction of the transpositions are replaced by 'reversals'. The model is motivated by statistical physics, where it plays a role in stochastic representations of xxz-models. We prove convergence to PD(1/2) of the rescaled cycle sizes, above the critical point for the appearance of macroscopic cycles. This extends a result of Schramm on convergence to PD(1) for the usual interchange process.
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| 20. |
- Briedis, Martins, et al.
(författare)
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Broad-scale patterns of the Afro-Palaearctic landbird migration
- 2020
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Ingår i: Global Ecology and Biogeography. - : WILEY. - 1466-822X .- 1466-8238. ; 29:4, s. 722-735
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Knowledge of broad-scale biogeographical patterns of animal migration is important for understanding ecological drivers of migratory behaviours. Here, we present a flyway-scale assessment of the spatial structure and seasonal dynamics of the Afro-Palaearctic bird migration system and explore how phenology of the environment guides long-distance migration.Location: Europe and Africa.Time period: 2009-2017.Major taxa studied: Birds.Methods: We compiled an individual-based dataset comprising 23 passerine and near-passerine species of 55 European breeding populations, in which a total of 564 individuals were tracked during migration between Europe and sub-Saharan Africa. In addition, we used remotely sensed primary productivity data (the normalized difference vegetation index) to estimate the timing of vegetation green-up in spring and senescence in autumn across Europe. First, we described how individual breeding and non-breeding sites and the migratory flyways link geographically. Second, we examined how the timing of migration along the two major Afro-Palaearctic flyways is tuned with vegetation phenology at the breeding sites.Results: We found the longitudes of individual breeding and non-breeding sites to be related in a strongly positive manner, whereas the latitudes of breeding and non-breeding sites were related negatively. In autumn, migration commenced ahead of vegetation senescence, and the timing of migration was 5-7 days earlier along the Western flyway compared with the Eastern flyway. In spring, the time of arrival at breeding sites was c. 1.5 days later for each degree northwards and 6-7 days later along the Eastern compared with the Western flyway, reflecting the later spring green-up at higher latitudes and more eastern longitudes.Main conclusions: Migration of the Afro-Palaearctic landbirds follows a longitudinally parallel leapfrog migration pattern, whereby migrants track vegetation green-up in spring but depart before vegetation senescence in autumn. The degree of continentality along migration routes and at the breeding sites of the birds influences the timing of migration on a broad scale.
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| 21. |
- Bruhn, H., et al.
(författare)
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Improved survival of Swedish glioblastoma patients treated according to Stupp
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : WILEY. - 0001-6314 .- 1600-0404. ; 138:4, s. 332-337
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe median survival in glioblastoma (GBM) patients used to be less than 1year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jonkoping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. Material and MethodThis study includes all patients from the county of Jonkoping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. ResultsThe mean survival was 110days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344days, Pamp;lt;.001) than in the 2006-2012 cohort (mean 220 vs 397days, P=.02). ConclusionSurvival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.
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| 22. |
- Bulakei, Omer, et al.
(författare)
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Agile Resource Management for 5G A METIS-II Perspective
- 2015
-
Ingår i: 2015 IEEE CONFERENCE ON STANDARDS FOR COMMUNICATIONS AND NETWORKING (CSCN). - 9781479989287 ; , s. 30-35
-
Konferensbidrag (refereegranskat)abstract
- An explosive growth in the demand for higher data rates and capacity along with diverse requirements set by massive and ultra-reliable machine-type communications are the main drivers behind the development on new access technologies as part of the fifth generation (5G) networks. Currently, different air interface (AIF) and/or AIF variants, optimized based on the frequency band of operation and use case, are envisioned for such a network. Developing an agile resource management framework for 5G networks is one of the main goals of the METIS-II project. The METIS-II project builds strongly upon the EU flagship project METIS, which has laid the foundation of 5G. This framework will take into account the multi-link and multi-layer constraints currently envisioned for 5G. In this paper, we provide our first insights into agile resource management and the associated synchronous control functions. We will discuss the essential building blocks in terms of technology enablers and their mapping to 5G services and deployments. The introduced agile resource management framework for 5G is expected to enable enhanced interference management, dynamic traffic steering, fast radio access network (RAN) moderation, efficient context management, and optimized integration with legacy networks.
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| 23. |
- Calkins, D. J., et al.
(författare)
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The challenge of regenerative therapies for the optic nerve in glaucoma
- 2017
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Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 157, s. 28-33
-
Tidskriftsartikel (refereegranskat)abstract
- This review arose from a discussion of regenerative therapies to treat optic nerve degeneration in glaucoma at the 2015 Lasker/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration. In addition to the authors, participants included Jonathan Crowston, Andrew Huberman, Elaine Johnson, Richard Lu, Hemai Phatnami, Rebecca Sappington, and Don Zack. Glaucoma is a neurodegenerative disease of the optic nerve, and is the leading cause of irreversible blindness worldwide. The disease progresses as sensitivity to intraocular pressure (IOP) is conveyed through the optic nerve head to distal retinal ganglion cell (RGC) projections. Because the nerve and retina are components of the central nervous system (CNS), their intrinsic regenerative capacity is limited. However, recent research in regenerative therapies has resulted in multiple breakthroughs that may unlock the optic nerve's regenerative potential. Increasing levels of Schwann-cell derived trophic factors and reducing potent cell-intrinsic suppressors of regeneration have resulted in axonal regeneration even beyond the optic chiasm. Despite this success, many challenges remain. RGC axons must be able to form new connections with their appropriate targets in central brain regions and these connections must be retinotopically correct. Furthermore, for new axons penetrating the optic projection, oligodendrocyte glia must provide myelination. Additionally, reactive gliosis and inflammation that increase the regenerative capacity must be outweigh pro-apoptotic processes to create an environment within which maximal regeneration can occur. (C) 2017 Elsevier Ltd. All rights reserved.
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| 24. |
- Chen, Yikai, et al.
(författare)
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Benchmark problem definition and cross-validation for characteristic mode solvers
- 2018
-
Ingår i: European Conference on Antennas and Propagation (EuCAP), 2018.. - : Institution of Engineering and Technology. - 9781785618161
-
Konferensbidrag (refereegranskat)abstract
- In October 2016, the Special Interest Group on Theory of Characteristic Modes (TCM) initiated a coordinated effort to perform benchmarking work for characteristic mode (CM) analysis. The primary purpose is to help improve the reliability and capability of existing CM solvers and to provide the means for validating future tools. Significant progress has already been made in this joint activity. In particular, this paper describes several benchmark problems that were defined and analyzes some results from the cross-validations of different CM solvers using these problems. The results show that despite differences in the implementation details, good agreement is observed in the calculated eigenvalues and eigencurrents across the solvers. Finally, it is concluded that future work should focus on understanding the impact of common parameters and output settings to further reduce variability in the results.
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| 25. |
- Conti, Diego M., et al.
(författare)
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A EUFOREA comment on a lost comorbidity of asthma
- 2023
-
Ingår i: Allergy, Asthma and Clinical Immunology. - 1710-1484. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- “Epidemiology of comorbidities and their association with asthma control” (Tomisa, G., Horváth, A., Sánta, B. et al. Epidemiology of comorbidities and their association with asthma control. Allergy Asthma Clin Immunol 17, 95 (2021). https://doi.org/10.1186/s13223-021-00598-3) is an interesting paper reflecting data collection from more than 12,000 asthmatic patients in Hungary regarding their condition and associated comorbidities. We found it valuable that the paper provides an overview of asthma comorbidities not usually considered in similar reports. Nevertheless, we believe that chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP or CRSsNP) should have been listed due to its high incidence and prevalence, its association with asthma which is also endorsed in both GINA and EPOS, as well as in several peer-reviewed scientific papers, and to reflect the role of this comorbidity in poor control and a most severe presentation of asthma for the patient. Consequently, several targeted therapies (especially monoclonal antibodies) used for several years in severe forms of asthma are now indicated also for the effective treatment of nasal polyps.
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| 26. |
- Diamant, Ulla-Britt, et al.
(författare)
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Two automatic QT algorithms compared with manual measurement in identification of long QT syndrome
- 2010
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 43:1, s. 25-30
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Long QT syndrome (LQTS) is an inherited disorder that increases the risk of syncope and malignant ventricular arrhythmias, which may result in sudden death.METHODS: We compared manual measurement by 4 observers (QT(manual)) and 3 computerized measurements for QT interval accuracy in the diagnosis of LQTS: 1. QT measured from the vector magnitude calculated from the 3 averaged orthogonal leads X, Y, and Z (QTVCG) and classified using the same predefined QTc cut-points for classification of QT prolongation as in manual measurements; 2. QT measured by a 12-lead electrocardiogram (ECG) program (QTECG) and subsequently classified using the same cut-points as in (1) above; 3. The same QT value as in (2) above, automatically classified by a 12-lead ECG program with thresholds for QT prolongation adjusted for age and sex (QTinterpret). The population consisted of 94 genetically confirmed carriers of KCNQ1 (LQT1) and KCNH2 (LQT2) mutations and a combined control group of 28 genetically confirmed noncarriers and 66 unrelated healthy volunteers.RESULTS: QT(VCG) provided the best combination of sensitivity (89%) and specificity (90%) in diagnosing LQTS, with 0.948 as the area under the receiver operating characteristic curve. The evaluation of QT measurement by the 4 observers revealed a high interreader variability, and only 1 of 4 observers showed acceptable level of agreement in LQTS mutation carrier identification (kappa coefficient >0.75).CONCLUSION: Automatic QT measurement by the Mida1000/CoroNet system (Ortivus AB, Danderyd, Sweden) is an accurate, efficient, and easily applied method for initial screening for LQTS.
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| 27. |
- Fricke, Tabea C., et al.
(författare)
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Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:48, s. 24359-24365
-
Tidskriftsartikel (refereegranskat)abstract
- Thermosensitive transient receptor potential (TRP) ion channels detect changes in ambient temperature to regulate body temperature and temperature-dependent cellular activity. Rodent orthologs of TRP vanilloid 2 (TRPV2) are activated by nonphysiological heat exceeding 50 °C, and human TRPV2 is heat-insensitive. TRPV2 is required for phagocytic activity of macrophages which are rarely exposed to excessive heat, but what activates TRPV2 in vivo remains elusive. Here we describe the molecular mechanism of an oxidation-induced temperature-dependent gating of TRPV2. While high concentrations of H2O2 induce a modest sensitization of heat-induced inward currents, the oxidant chloramine-T (ChT), ultraviolet A light, and photosensitizing agents producing reactive oxygen species (ROS) activate and sensitize TRPV2. This oxidation-induced activation also occurs in excised inside-out membrane patches, indicating a direct effect on TRPV2. The reducing agent dithiothreitol (DTT) in combination with methionine sulfoxide reductase partially reverses ChT-induced sensitization, and the substitution of the methionine (M) residues M528 and M607 to isoleucine almost abolishes oxidation-induced gating of rat TRPV2. Mass spectrometry on purified rat TRPV2 protein confirms oxidation of these residues. Finally, macrophages generate TRPV2-like heat-induced inward currents upon oxidation and exhibit reduced phagocytosis when exposed to the TRP channel inhibitor ruthenium red (RR) or to DTT. In summary, our data reveal a methionine-dependent redox sensitivity of TRPV2 which may be an important endogenous mechanism for regulation of TRPV2 activity and account for its pivotal role for phagocytosis in macrophages.
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| 28. |
- Girovsky, Jan, et al.
(författare)
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Long-range ferrimagnetic order in a two-dimensional supramolecular Kondo lattice
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Realization of long-range magnetic order in surface-supported two-dimensional systems has been challenging, mainly due to the competition between fundamental magnetic interactions as the short-range Kondo effect and spin-stabilizing magnetic exchange interactions. Spin-bearing molecules on conducting substrates represent a rich platform to investigate the interplay of these fundamental magnetic interactions. Here we demonstrate the direct observation of long-range ferrimagnetic order emerging in a two-dimensional supramolecular Kondo lattice. The lattice consists of paramagnetic hexadeca-fluorinated iron phthalocyanine (FeFPc) and manganese phthalocyanine (MnPc) molecules co-assembled into a checkerboard pattern on single-crystalline Au(111) substrates. Remarkably, the remanent magnetic moments are oriented in the out-of-plane direction with significant contribution from orbital moments. First-principles calculations reveal that the FeFPc-MnPc antiferromagnetic nearest-neighbour coupling is mediated by the Ruderman-Kittel-Kasuya-Yosida exchange interaction via the Au substrate electronic states. Our findings suggest the use of molecular frameworks to engineer novel low-dimensional magnetically ordered materials and their application in molecular quantum devices.
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| 29. |
- Grosche, A., et al.
(författare)
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Versatile and Simple Approach to Determine Astrocyte Territories in Mouse Neocortex and Hippocampus
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Besides their neuronal support functions, astrocytes are active partners in neuronal information processing. The typical territorial structure of astrocytes (the volume of neuropil occupied by a single astrocyte) is pivotal for many aspects of glia-neuron interactions. Methods: Individual astrocyte territorial volumes are measured by Golgi impregnation, and astrocyte densities are determined by S100 beta immunolabeling. These data are compared with results from conventionally applied methods such as dye filling and determination of the density of astrocyte networks by biocytin loading. Finally, we implemented our new approach to investigate age-related changes in astrocyte territories in the cortex and hippocampus of 5- and 21-month-old mice. Results: The data obtained by our simplified approach based on Golgi impregnation were compared to previously published dye filling experiments, and yielded remarkably comparable results regarding astrocyte territorial volumes. Moreover, we found that almost all coupled astrocytes (as indicated by biocytin loading) were immunopositive for S100 beta. A first application of this new experimental approach gives insight in age-dependent changes in astrocyte territorial volumes. They increased with age, while cell densities remained stable. In 5-month-old mice, the overlap factor was close to 1, revealing little or no interdigitation of astrocyte territories. However, in 21-month-old mice, the overlap factor was more than 2, suggesting that processes of adjacent astrocytes interdigitate. Conclusion: Here we verified the usability of a simple, versatile method for assessing astrocyte territories and the overlap factor between adjacent territories. Second, we found that there is an age-related increase in territorial volumes of astrocytes that leads to loss of the strict organization in non-overlapping territories. Future studies should elucidate the physiological relevance of this adaptive reaction of astrocytes in the aging brain and the methods presented in this study might be a powerful tool to do so.
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| 30. |
- Hol, E. M., et al.
(författare)
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Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system
- 2015
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Ingår i: Current Opinion in Cell Biology. - : Elsevier BV. - 0955-0674. ; 32, s. 121-130
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Tidskriftsartikel (refereegranskat)abstract
- Glial fibrillary acidic protein (GFAP) is the hallmark intermediate filament (IF; also known as nanofilament) protein in astrocytes, a main type of glial cells in the central nervous system (CNS). Astrocytes have a range of control and homeostatic functions in health and disease. Astrocytes assume a reactive phenotype in acute CNS trauma, ischemia, and in neurodegenerative diseases. This coincides with an upregulation and rearrangement of the IFs, which form a highly complex system composed of GFAP (10 isoforms), vimentin, synemin, and nestin. We begin to unravel the function of the IF system of astrocytes and in this review we discuss its role as an important crisis-command center coordinating cell responses in situations connected to cellular stress, which is a central component of many neurological diseases.
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| 31. |
- Höglund, Niklas, et al.
(författare)
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Cardioversion of atrial fibrillation does not affect obstructive sleep apnea
- 2017
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 122:2, s. 114-118
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sleep apnea is common in patients with atrial fibrillation, but the effect of the cardioversion of atrial fibrillation to sinus rhythm on central and obstructive apneas is mainly unknown. The primary aim of the study was to analyze the association between cardioversion of atrial fibrillation and sleep apneas, to investigate whether obstructive or central sleep apneas are reduced following cardioversion. A secondary objective was to study the effect on sleep quality. Methods: Twenty-three patients with atrial fibrillation were investigated using overnight polysomnography, including esophagus pressure monitoring and ECG, before and after the cardioversion of persistent atrial fibrillation. Results: Obstructive sleep apnea occurred in 17/23 patients (74%), and central sleep apnea in 6/23 patients (26%). Five patients had both obstructive and central sleep apnea. Sinus rhythm at follow-up was achieved in 16 patients. The obstructive apnea-hypopnea index, central apnea-hypopnea index, and the number of patients with obstructive or central sleep apnea did not differ before and after restoration of sinus rhythm. Sleep time, sleep efficiency, time in different sleep stages, and subjective daytime sleepiness were normal and unaffected by cardioversion. Conclusions: Both obstructive and central sleep apneas are highly prevalent in patients with persistent atrial fibrillation. Obstructive sleep apneas are unaffected by the cardioversion of atrial fibrillation to sinus rhythm. The sleep pattern is normal and unaffected by cardioversion in patients with atrial fibrillation. Clinical Trial Registration: Trial number NCT00429884.
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| 32. |
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| 33. |
- Jones, William, 1989-, et al.
(författare)
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Interspecific transfer of parasites following a range-shift in Ficedula flycatchers
- 2018
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 8:23, s. 12183-12192
-
Tidskriftsartikel (refereegranskat)abstract
- Human-induced climate change is expected to cause major biotic changes in species distributions and thereby including escalation of novel host-parasite associations. Closely related host species that come into secondary contact are especially likely to exchange parasites and pathogens. Both the Enemy Release Hypothesis (where invading hosts escape their original parasites) and the Novel Weapon Hypothesis (where invading hosts bring new parasites that have detrimental effects on native hosts) predict that the local host will be most likely to experience a disadvantage. However, few studies evaluate the occurrence of interspecific parasite transfer by performing wide-scale geographic sampling of pathogen lineages, both within and far from host contact zones. In this study, we investigate how haemosporidian (avian malaria) prevalence and lineage diversity vary in two, closely related species of passerine birds; the pied flycatcher Ficedula hypoleuca and the collared flycatcher F. albicollis in both allopatry and sympatry. We find that host species is generally a better predictor of parasite diversity than location, but both prevalence and diversity of parasites vary widely among populations of the same bird species. We also find a limited and unidirectional transfer of parasites from pied flycatchers to collared flycatchers in a recent contact zone. This study therefore rejects both the Enemy Release Hypothesis and the Novel Weapon Hypothesis and highlights the complexity and importance of studying host-parasite relationships in an era of global climate change and species range shifts.
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| 34. |
- Karampatsi, D., et al.
(författare)
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Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke
- 2021
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Post-stroke functional recovery is severely impaired by type 2 diabetes (T2D). This is an important clinical problem since T2D is one of the most common diseases. Because weight loss-based strategies have been shown to decrease stroke risk in people with T2D, we aimed to investigate whether diet-induced weight loss can also improve post-stroke functional recovery and identify some of the underlying mechanisms. Methods T2D/obesity was induced by 6 months of high-fat diet (HFD). Weight loss was achieved by a short- or long-term dietary change, replacing HFD with standard diet for 2 or 4 months, respectively. Stroke was induced by middle cerebral artery occlusion and post-stroke recovery was assessed by sensorimotor tests. Mechanisms involved in neurovascular damage in the post-stroke recovery phase, i.e. neuroinflammation, impaired angiogenesis and cellular atrophy of GABAergic parvalbumin (PV)+ interneurons were assessed by immunohistochemistry/quantitative microscopy. Results Both short- and long-term dietary change led to similar weight loss. However, only the latter enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and insulin resistance, and with the reduction of T2D-induced cellular atrophy of PV+ interneurons. Moreover, stroke recovery was associated with decreased T2D-induced neuroinflammation and reduced astrocyte reactivity in the contralateral striatum. Conclusion The global diabetes epidemic will dramatically increase the number of people in need of post-stroke treatment and care. Our results suggest that diet-induced weight loss leading to pre-stroke normalization of glucose metabolism has great potential to reduce the sequelae of stroke in the diabetic population.
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| 35. |
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| 36. |
- Kesek, Milos, et al.
(författare)
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Increased risk of late pacemaker implantation after ablation for atrioventricular nodal reentry tachycardia : A 10-year follow-up of a nationwide cohort
- 2019
-
Ingår i: Heart Rhythm. - : Elsevier. - 1547-5271 .- 1556-3871. ; 16:8, s. 1182-1188
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Catheter ablation of the slow pathway is the standard treatment of atrioventricular nodal reentry tachycardia (AVNRT) with a well described low risk of periprocedural atrioventricular block. Less is known about the risk of pacemaker implantation late after ablation.Objective: We aimed to quantify the risk of late pacemaker implantation in a countrywide cohort undergoing first-time ablation for AVNRT.Methods: All patients undergoing first-time ablation for AVNRT in Sweden from 2004 to 2014 were identified from the Swedish catheter ablation registry and matched against the Swedish Pacemaker and ICD registry. The cohort was compared to patients ablated for an accessory pathway (AP) and to matched controls.Results: During follow-up of 2039 days, pacemaker was implanted later than 30 days after ablation in 96 of 6842 patients with AVNRT (1.4%), 29 of 4065 patients with AP (0.7%) (P = .001), and 124 of 33,270 controls (0.4%) (P < .00001). A periprocedural pacemaker (≤30 days postablation) was implanted in 32 of 6877 patients with AVNRT (0.5%) and 9 of 4079 patients with AP (0.2%) (P = .05). With cryoablation, 5 patients needed periprocedural pacemaker implantation. Pacemakers were implanted before ablation in 88 of 6977 patients with AVNRT (1.3%) and 11 of 4100 patients with AP (0.3%); the prevalence of pacemaker implants in controls was 124 of 33,270 (0.4%) (P < .00001 for both comparisons).Conclusion: The risk of late pacemaker implantation after AVNRT ablation was low but 3 times higher than that in the control population and 3 times higher than the risk of periprocedural pacemaker implantation. Similar results were observed with cryoablation and radiofrequency ablation. Ablation may not be the cause of increased late pacemaker implantation risk.
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| 37. |
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| 38. |
- Kesek, Milos, et al.
(författare)
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Two Cases of LQT Syndrome with Malignant Syncope after Switch from Propranolol to Bisoprolol
- 2016
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Ingår i: Pacing and Clinical Electrophysiology. - : Wiley. - 0147-8389 .- 1540-8159. ; 39:3, s. 305-306
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Tidskriftsartikel (refereegranskat)abstract
- Propranolol in slow-release form has been the first-line treatment in long QT (LQT) until it was withdrawn from the market. We describe two cases where a switch to bisoprolol resulted in worsening of arrhythmia control: A man with LQT2, asymptomatic on propranolol, experienced syncope after switching to bisoprolol 5 mg daily. He switched back to propranolol and has remained asymptomatic during subsequent 12 months. A man with classical Jervell Lange-Nielsen syndrome, previous gangliectomy, and ICD implantation, switched to bisoprolol 5 mg daily. Four months later he experienced a tachycardia storm. He switched back to propranolol and has remained free from arrhythmias during subsequent 12 months.
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| 39. |
- Kesek, Milos, et al.
(författare)
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U22, a protocol to quantify symptoms associated with supraventricular tachycardia.
- 2009
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Ingår i: Pacing and Clinical Electrophysiology. - : Wiley. - 0147-8389 .- 1540-8159. ; 32:S1, s. S105-S108
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The main indication for ablation of supraventricular tachyarrhythmias (SVTA) is symptomatic relief. Specific paroxysmal symptoms cannot be quantified with general measures of quality of life, such as with the SF-36 questionnaire. U22 is a new protocol which measures the effects of arrhythmia on well-being, the intensity of discomfort during an episode, the type and temporal characteristics of dominant symptoms, and the duration and frequency of episodes. Discrete 0-10 scales are used. Unlike SF-36, U22 can be used in individual patients. METHODS: U22 and SF-36 protocols were used in the symptomatic evaluation of 88 patients (mean age = 49.6 +/- 16.4 years; 43 men), who underwent catheter ablation of SVTA. Results: The U22 scores (SD) for (a) well-being (10 being best), (b) effects of arrhythmia on well-being (10 being worst), and (c) discomfort during arrhythmia (10 being worst) were 5.6 (2.7), 7.5 (2.8), and 8.0 (2.4), respectively. For comparison, the physical and mental component summaries of SF-36 were 45.3 (11.0) and 45.2 (12.1), respectively, slightly lower than the expected normal of 50. The intensity of dominant symptom scored by U22 was 9.7 (1.2), 10 being worst. In 29% of patients > or =4 symptoms were equally dominant. Multiple dominant symptoms in U22 were associated with a low general well-being in SF-36. CONCLUSION: We found U22 useful to quantify symptoms associated with SVTA.
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| 40. |
- Khasanov, Rustem, et al.
(författare)
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Superconducting nature of the Bi-II phase of elemental bismuth
- 2019
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 99:17
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Tidskriftsartikel (refereegranskat)abstract
- The superconductivity in the Bi-II phase of elemental bismuth (transition temperature T-c similar or equal to 3.92 K at pressure p similar or equal to 2.80 GPa) was studied experimentally by means of the muon-spin rotation as well as theoretically by using the Eliashberg theory in combination with density functional theory calculations. Experiments reveal that Bi-II is a type-I superconductor with a zero temperature value of the thermodynamic critical field B-c(0) similar or equal to 31.97 mT. The Eliashberg theory approach provides a good agreement with the experimental T-c and the temperature evolution of B-c . The estimated value for the retardation (coupling) parameter k(B)T(c)/omega(In) approximate to 0.07 (omega(In) is the logarithmically averaged phonon frequency) suggests that Bi-II is an intermediately coupled superconductor.
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| 41. |
- Kraft, Andrew W, et al.
(författare)
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Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice.
- 2013
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 27:1, s. 187-98
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of aggregated amyloid-β (Aβ) in amyloid plaques is a neuropathological hallmark of Alzheimer's disease (AD). Reactive astrocytes are intimately associated with amyloid plaques; however, their role in AD pathogenesis is unclear. We deleted the genes encoding two intermediate filament proteins required for astrocyte activation-glial fibrillary acid protein (Gfap) and vimentin (Vim)-in transgenic mice expressing mutant human amyloid precursor protein and presenilin-1 (APP/PS1). The gene deletions increased amyloid plaque load: APP/PS1 Gfap(-/-)Vim(-/-) mice had twice the plaque load of APP/PS1 Gfap(+/+)Vim(+/+) mice at 8 and 12 mo of age. APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation. Astrocyte morphology was markedly altered by the deletions: wild-type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas Gfap(-/-)Vim(-/-) astrocytes had little process hypertrophy and lacked contact with adjacent plaques. Moreover, Gfap and Vim gene deletion resulted in a marked increase in dystrophic neurites (2- to 3-fold higher than APP/PS1 Gfap(+/+)Vim(+/+) mice), even after normalization for amyloid load. These results suggest that astrocyte activation limits plaque growth and attenuates plaque-related dystrophic neurites. These activities may require intimate contact between astrocyte and plaque.-Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., Cirrito, J. R., Holtzman, D. M., Kim, J., Pekny, M., Lee, J.-M. Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice.
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| 42. |
- Maes, Dirk, et al.
(författare)
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Integrating national Red Lists for prioritising conservation actions for European butterflies
- 2019
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Ingår i: Journal of Insect Conservation. - : Springer Science and Business Media LLC. - 1366-638X .- 1572-9753. ; 23:2, s. 301-330
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Tidskriftsartikel (refereegranskat)abstract
- Red Lists are very valuable tools in nature conservation at global, continental and (sub-) national scales. In an attempt to prioritise conservation actions for European butterflies, we compiled a database with species lists and Red Lists of all European countries, including the Macaronesian archipelagos (Azores, Madeira and Canary Islands). In total, we compiled national species lists for 42 countries and national Red Lists for 34 of these. The most species-rich countries in Europe are Italy, Russia and France with more than 250 species each. Endemic species are mainly found on the Macaronesian archipelagos and on the Mediterranean islands. By attributing numerical values proportionate to the threat statuses in the different national Red List categories, we calculated a mean Red List value for every country (cRLV) and a weighted Red List value for every species (wsRLV) using the square root of the country’s area as a weighting factor. Countries with the highest cRLV were industrialised (NW) European countries such as the Netherlands, Belgium, the Czech Republic and Denmark, whereas large Mediterranean countries such as Spain and Italy had the lowest cRLV. Species for which a Red List assessment was available in at least two European countries and with a relatively high wsRLV (≥ 50) are Colias myrmidone, Pseudochazara orestes, Tomares nogelii, Colias chrysotheme and Coenonympha oedippus. We compared these wsRLVs with the species statuses on the European Red List to identify possible mismatches. We discuss how this complementary method can help to prioritise butterfly conservation on the continental and/or the (sub-)national scale.
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| 43. |
- Marković, Rastko S., et al.
(författare)
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Aeolian dynamics at the northern edge of Deliblato (Banat) Sand Sea, Vojvodina, Serbia, at the time of the last deglaciation
- 2024
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Ingår i: Quaternary Research (United States). - 0033-5894.
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Tidskriftsartikel (refereegranskat)abstract
- The Deliblato (Banat) Sand Sea, which is one of the largest areas of aeolian sand in Europe, is located near the Iron Gate, which marks the crossing of the Danube River through the biggest gorge of this river. Here, Danubian alluvium has served as the sand source for the Banat Sand Sea, which was formed primarily through southeasterly (Košava) winds. Utilizing a multi-proxy approach, the objective of this study is to gain a better understanding of the environmental dynamics of the Banat Sand Sea. To achieve this goal, we conducted an analysis of an archive representing an approximately 20-m-thick dune formation on the northern edge of this dune field. Using optically stimulated luminescence (OSL) dating, we calculated aeolian sedimentation rates and dune ages. Sand was deposited here approximately between 17 ka and 13 ka. Magnetic susceptibility, grain size, and colorimetric analyses were interpreted in terms of local paleoenvironmental conditions. Calculated sedimentation rates (SR) indicate intensive aeolian deposition during the study period that range from 483 cm/ka to 502 cm/ka. We compared our data with regional and other European archives, as well as with climatic variations recorded in the Greenland ice core North Greenland Ice Core Project (NGRIP).
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Moparthi, Lavanya, et al.
(författare)
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Electrophile-Induced Conformational Switch of the Human TRPA1 Ion Channel Detected by Mass Spectrometry
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:18
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Tidskriftsartikel (refereegranskat)abstract
- The human Transient Receptor Potential A1 (hTRPA1) ion channel, also known as the wasabi receptor, acts as a biosensor of various potentially harmful stimuli. It is activated by a wide range of chemicals, including the electrophilic compound N-methylmaleimide (NMM), but the mechanism of activation is not fully understood. Here, we used mass spectrometry to map and quantify the covalent labeling in hTRPA1 at three different concentrations of NMM. A functional truncated version of hTRPA1 (Delta 1-688 hTRPA1), lacking the large N-terminal ankyrin repeat domain (ARD), was also assessed in the same way. In the full length hTRPA1, the labeling of different cysteines ranged from nil up to 95% already at the lowest concentration of NMM, suggesting large differences in reactivity of the thiols. Most important, the labeling of some cysteine residues increased while others decreased with the concentration of NMM, both in the full length and the truncated protein. These findings indicate a conformational switch of the proteins, possibly associated with activation or desensitization of the ion channel. In addition, several lysines in the transmembrane domain and the proximal N-terminal region were labeled by NMM, raising the possibility that lysines are also key targets for electrophilic activation of hTRPA1.
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| 48. |
- Moparthi, Lavanya, et al.
(författare)
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Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Thermosensitive Transient Receptor Potential (TRP) channels are believed to respond to either cold or heat. In the case of TRP subtype A1 (TRPA1), there seems to be a species-dependent divergence in temperature sensation as non-mammalian TRPA1 is heat-sensitive whereas mammalian TRPA1 is sensitive to cold. It has been speculated but never experimentally proven that TRPA1 and other temperature-sensitive ion channels have the inherent capability of responding to both cold and heat. Here we show that redox modification and ligands affect human TRPA1 (hTRPA1) cold and heat sensing properties in lipid bilayer and whole-cell patch-clamp recordings as well as heat-evoked TRPA1-dependent calcitonin gene-related peptide (CGRP) release from mouse trachea. Studies of purified hTRPA1 intrinsic tryptophan fluorescence, in the absence of lipid bilayer, consolidate hTRPA1 as an intrinsic bidirectional thermosensor that is modified by the redox state and ligands. Thus, the heat sensing property of TRPA1 is conserved in mammalians, in which TRPA1 may contribute to sensing warmth and uncomfortable heat in addition to noxious cold.
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| 49. |
- Moparthi, Lavanya, et al.
(författare)
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The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- TRP channels sense temperatures ranging from noxious cold to noxious heat. Whether specialized TRP thermosensor modules exist and how they control channel pore gating is unknown. We studied purified human TRPA1 (hTRPA1) truncated proteins to gain insight into the temperature gating of hTRPA1. In patch-clamp bilayer recordings, ∆1-688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), was more sensitive to cold and heat, whereas ∆1-854 hTRPA1, also lacking the S1-S4 voltage sensing-like domain (VSLD), gained sensitivity to cold but lost its heat sensitivity. In hTRPA1 intrinsic tryptophan fluorescence studies, cold and heat evoked rearrangement of VSLD and the C-terminus domain distal to the transmembrane pore domain S5-S6 (CTD). In whole-cell electrophysiology experiments, replacement of the CTD located cysteines 1021 and 1025 with alanine modulated hTRPA1 cold responses. It is proposed that hTRPA1 CTD harbors cold and heat sensitive domains allosterically coupled to the S5-S6 pore region and the VSLD, respectively.
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| 50. |
- Pajares, M. A., et al.
(författare)
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Alexander disease: the road ahead
- 2023
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Ingår i: Neural Regeneration Research. - 1673-5374. ; 18:10, s. 2156-60
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Tidskriftsartikel (refereegranskat)abstract
- Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein, a type III intermediate filament protein expressed in astrocytes. Both early (infantile or juvenile) and adult onsets of the disease are known and, in both cases, astrocytes present characteristic aggregates, named Rosenthal fibers. Mutations are spread along the glial fibrillary acidic protein sequence disrupting the typical filament network in a dominant manner. Although the presence of aggregates suggests a proteostasis problem of the mutant forms, this behavior is also observed when the expression of wild-type glial fibrillary acidic protein is increased. Additionally, several isoforms of glial fibrillary acidic protein have been described to date, while the impact of the mutations on their expression and proportion has not been exhaustively studied. Moreover, the posttranslational modification patterns and/or the protein-protein interaction networks of the glial fibrillary acidic protein mutants may be altered, leading to functional changes that may modify the morphology, positioning, and/or the function of several organelles, in turn, impairing astrocyte normal function and subsequently affecting neurons. In particular, mitochondrial function, redox balance and susceptibility to oxidative stress may contribute to the derangement of glial fibrillary acidic protein mutant-expressing astrocytes. To study the disease and to develop putative therapeutic strategies, several experimental models have been developed, a collection that is in constant growth. The fact that most cases of Alexander disease can be related to glial fibrillary acidic protein mutations, together with the availability of new and more relevant experimental models, holds promise for the design and assay of novel therapeutic strategies.
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