| 1. |
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| 2. |
- Bannatyne, B A, et al.
(författare)
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Inhibitory inputs to four types of spinocerebellar tract neurons in the cat spinal cord.
- 2012
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 226, s. 253-69
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar tract neurons are inhibited by various sources of input via pathways activated by descending tracts as well as peripheral afferents. Inhibition may be used to modulate transmission of excitatory information forwarded to the cerebellum. However it may also provide information on the degree of inhibition of motoneurons and on the operation of inhibitory premotor neurons. Our aim was to extend previous comparisons of morphological substrates of excitation of spinocerebellar neurons to inhibitory input. Contacts formed by inhibitory axon terminals were characterised as either GABAergic, glycinergic or both GABAergic/glycinergic by using antibodies against vesicular GABA transporter, glutamic acid decarboxylase and gephyrin. Quantitative analysis revealed the presence of much higher proportions of inhibitory contacts when compared with excitatory contacts on spinal border (SB) neurons. However similar proportions of inhibitory and excitatory contacts were associated with ventral spinocerebellar tract (VSCT) and dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and the dorsal horn (dhDSCT). In all of the cells, the majority of inhibitory terminals were glycinergic. The density of contacts was higher on somata and proximal versus distal dendrites of SB and VSCT neurons but more evenly distributed in ccDSCT and dhDSCT neurons. Variations in the density and distribution of inhibitory contacts found in this study may reflect differences in information on inhibitory processes forwarded by subtypes of spinocerebellar tract neurons to the cerebellum.
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| 3. |
- Galea, Mary Pauline, et al.
(författare)
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Bilateral postsynaptic actions of pyramidal tract and reticulospinal neurons on feline erector spinae motoneurons.
- 2010
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Ingår i: The Journal of neuroscience. - 1529-2401. ; 30:3, s. 858-869
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Tidskriftsartikel (refereegranskat)abstract
- Trunk muscles are important for postural adjustments associated with voluntary movements but little has been done to analyze mechanisms of supraspinal control of these muscles at a cellular level. The present study therefore aimed to investigate the input from pyramidal tract (PT) neurons to motoneurons of the musculus longissimus lumborum of the erector spinae and to analyze to what extent it is relayed by reticulospinal (RS) neurons. Intracellular records from motoneurons were used to evaluate effects of electrical stimulation of medullary pyramids and of axons of RS neurons descending in the medial longitudinal fasciculus (MLF). The results revealed that similar synaptic actions were evoked from the ipsilateral and contralateral PTs, including disynaptic and trisynaptic EPSPs and trisynaptic IPSPs. Stimulation of the MLF-evoked monosynaptic and disynaptic EPSPs and disynaptic or trisynaptic IPSPs in the same motoneurons. All short-latency PSPs of PT origin were abolished by transection of the MLF, while they remained after transection of PT fibers at a spinal level. Hence, RS neurons might serve as the main relay neurons of the most direct PT actions on musculus (m.) longissimus. However, longer-latency IPSPs remaining after MLF or PT spinal lesions and after ipsilateral or contralateral hemisection of spinal cord indicate that PT actions are also mediated by ipsilaterally and/or contralaterally located spinal interneurons. The bilateral effects of PT stimulation thereby provide an explanation why trunk movements after unilateral injuries of PT neurons (e.g., stroke) are impaired to a lesser degree than movements of the extremities.
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| 4. |
- Hammar, Ingela, 1964, et al.
(författare)
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A trans-spinal loop between neurones in the reticular formation and in the cerebellum.
- 2011
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Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 589:Pt 3, s. 653-65
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Tidskriftsartikel (refereegranskat)abstract
- Voluntary limb movements are initiated in the brain but the neurones responsible for activating the muscles (motoneurones and interneurones) are located in the spinal cord. The spinal cord also contains neurones that provide the brain, and especially the cerebellum, with continuous information on effects of the descending commands. We show that one population of such neurones provide the cerebellum with information on how likely the brain's commands (mediated by descending reticulospinal neurones) are to be executed as planned, depending on the degree of inhibition of motoneurones. They may therefore play an important role in preventing errors in activation of motoneurones and thereby help the brain to correct its signals to the spinal cord before such errors have been committed.
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| 5. |
- Jankowska, Elzbieta, et al.
(författare)
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Do spinocerebellar neurones forward information on spinal actions of neurones in the feline red nucleus?
- 2011
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Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 589:Pt 23, s. 5727-39
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Tidskriftsartikel (refereegranskat)abstract
- Abstract We recently demonstrated that feline ventral spinocerebellar tract (VSCT) neurones monitor descending commands for voluntary movements initiated by pyramidal tract (PT) neurones as well as locomotor movements relayed by reticulospinal (RS) neurones. The aim of the present study was to examine whether VSCT neurones likewise monitor descending commands from the red nucleus (RN). Extracellular records from the spinal border (SB) subpopulation of VSCT neurons revealed that a third (31%) of SB neurones may be discharged by trains of stimuli applied in the RN. Moreover, when RN stimuli failed to discharge SB neurones they facilitated activation of some of these neurones by RS and/or PT neurones, while activation of other SB neurones was depressed. We propose that the facilitation and depression of actions of RS neurones by RN neurones might serve to reflect a higher or lower excitability of motoneurones and therefore a likely higher or lower efficacy of the RS descending commands, prompting the cerebellum to adjust the activation of reticulospinal neurones. Activation of SB neurones by RN stimuli alone would also allow monitoring and adjusting the RN descending commands. Intracellular records from SB neurones revealed both monosynaptic and disynaptic EPSPs and disynaptic IPSPs evoked by RN stimuli. The disynaptic actions remained following transection of axons of reticulospinal neurones within the medullary longitudinal fascicle (MLF) and were therefore taken to be relayed primarily by spinal neurones, in contrast to EPSPs and IPSPs evoked by PT stimuli found to be relayed by reticulospinal rather than spinal neurones.
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| 6. |
- Jankowska, Elzbieta, et al.
(författare)
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Processing information related to centrally initiated locomotor and voluntary movements by feline spinocerebellar neurones.
- 2011
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Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 589:Pt 23, s. 5709-25
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Feed-back information on centrally initiated movements is processed at both supraspinal and spinal levels and is forwarded by a variety of neurones. The aim of the present study was to examine how descending commands relayed by reticulospinal neurones are monitored by a population of spinocerebellar tract neurones. Our main question was whether a spinal border (SB) subpopulation of ventral spinocerebellar tract (VSCT) neurones monitor actions of reticulospinal neurones with input from the mesencephalic locomotor region (MLR) as well as from pyramidal tract (PT) neurones. In the majority of intracellularly recorded SB neurons, stimuli applied in the MLR and in the medullary pyramids evoked EPSPs in parallel with EPSPs evoked by stimulation of axons of reticulospinal neurones in the medial longitudinal fascicle (MLF). In extracellularly recorded neurones short trains of stimuli applied in the ipsilateral and contralateral pyramids potently facilitated discharges evoked from the MLF, as well as EPSPs recorded intracellularly. In both cases the facilitation involved the disynaptic but not the monosynaptic actions. These results indicate that reticulospinal neurones activating SB neurones (or more generally VSCT neurones) are co-excited by axon-collaterals of other reticulospinal neurones and by fibres stimulated within the MLR and PTs. The study leads to the conclusion that these spinocerebellar neurones monitor descending commands for centrally initiated voluntary as well as locomotor movements relayed by reticulospinal neurones. Thereby they may provide the cerebellum with feed-back information on the likely outcome of these commands and any corrections needed to avoid errors in the issuing movements.
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| 7. |
- Kronqvist, Nina, et al.
(författare)
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Combining phage and staphylococcal surface display for generation of ErbB3-specific Affibody molecules
- 2011
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 24:4, s. 385-396
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that the catalytically inactive ErbB3 (HER3) protein plays a fundamental role in normal tyrosine kinase receptor signaling as well as in aberrant functioning of these signaling pathways, resulting in several forms of human cancers. ErbB3 has recently also been implicated in resistance to ErbB2-targeting therapies. Here we report the generation of high-affinity ErbB3-specific Affibody molecules intended for future molecular imaging and biotherapeutic applications. Using a high-complexity phage-displayed Affibody library, a number of ErbB3 binders were isolated and specific cell-binding activity was demonstrated in immunofluorescence microscopic studies. Subsequently, a second-generation library was constructed based on sequences of the candidates from the phage display selection. By exploiting the sensitive affinity discrimination capacity of a novel bacterial surface display technology, the affinity of candidate Affibody molecules was further increased down to subnanomolar affinity. In summary, the demonstrated specific targeting of native ErbB3 receptor on human cancer cell lines as well as competition with the heregulin/ErbB3 interaction indicates that these novel biological agents may become useful tools for diagnostic and therapeutic targeting of ErbB3-expressing cancers. Our studies also highlight the powerful approach of combining the advantages of different display technologies for generation of functional high-affinity protein-based binders. Potential future applications, such as radionuclide-based diagnosis and treatment of human cancers are discussed.
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| 8. |
- Lundberg, Valeria, 1984, et al.
(författare)
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Converting a kraft pulp mill into a multi-product biorefinery: techno-economic analysis of a case mill
- 2014
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Ingår i: Clean Technologies and Environmental Policy. - : Springer Science and Business Media LLC. - 1618-954X .- 1618-9558. ; 16:7, s. 1411-1422
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Tidskriftsartikel (refereegranskat)abstract
- In this case study, we investigated the conversion of an existing Swedish kraft pulp mill to the production of dissolving pulp, with export of electricity, lignin, and a hemicellulose stream suitable for upgrading. By increasing the level of heat integration of the mill, it was possible to achieve self-sufficiency in terms of steam and to produce significant amounts of excess steam. The excess steam could facilitate the integration of a lignin separation plant or be used for power generation. The production of dissolving pulp requires a higher input of wood that is required for the same level of pulp production as is achieved with kraft pulp. For the studied mill, the batch digester was the main limitation for pulp production. Nevertheless, if the digester capacity was increased, then the level of pulp production could be maintained. In addition, the recovery boiler, causticization plant, and evaporation plant had sufficient capacities for preserving the same production level upon conversion, and could easily be upgraded to a certain degree through relatively simple measures for an increase in pulp production. However, increasing pulp production beyond that limit required extensive upgrades or investments in new equipment, which negatively affected annual earnings. Annual earnings were found to be also dependent upon the level of heat integration, type of by-product, and the costs for lignin and electricity. However, our results suggest that the optimal process configuration is more dependent upon other factors, such as the long-term vision of the company and policy instruments.
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| 9. |
- Lundin, Elin, 1983-, et al.
(författare)
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Factors affecting padlock probe efficiency
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Padlock probes have proved to be extremely versatile and useful molecular tools. They have unique properties that allow them to be used in various applications, ranging from diagnostic assays to spatially resolved transcriptomics. Padlock probes are used for detection of specific DNA or RNA sequences in enzymatic multistep assays. As the assays involve circularization and rolling circle amplification of the padlock probe, different factors play a role in the efficiency of the separate steps. Guidelines for how to design padlock probes have been lacking. We investigated how the length and the secondary structure of the different parts of the padlock probe affected its efficacy in the different steps of the assay as well as the impact on the total assay. The optimal length of the padlock probe is a compromise between a shorter total probe length, which leads to more efficient amplification and longer target specific sequence, which confers more efficient circularization. Complex secondary structure interfering with the detection motif or involving both the target-specific parts of the padlock probe seriously impair the assay efficiency. However, less complex secondary structures can be tolerated without significant efficiency loss. Taken together, the results present important considerations for the design of padlock probes and guidelines for how to improve the general detection efficiency.
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| 10. |
- Lundin, Elin, 1983-
(författare)
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RNA-based spatial characterization of cell and tissue heterogeneity
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Technical advances in cell biology have revolutionized the field of cell biology. With new technology it is now possible to address scientific questions in cell biology at the molecular level. Single-cell RNA-sequencing can reveal transcriptomic information for single cells and spatially resolved transcriptomic technology can visualize thousands or millions of cells and transcripts for spatial molecular profiling. The work in this thesis describes the technological development from traditional in situ hybridization to the current state-of-the-art technology for spatial multiplexed gene expression analysis. This development has enabled RNA-based molecular characterization of cells and tissues with the spatial dimension maintained. The work included in the thesis highlights the potential and the advantages of padlock-probe-based technology for spatial RNA-based profiling of cells and tissues. Furthermore, it demonstrates the possibilities arising from the inherent ability of padlock probes to distinguish between transcripts based on differences in single nucleotides.The study in paper I investigates the prevalence of Enterovirus species B in patients with Crohn’s disease by a chromogenic in situ hybridization assay combined with immunohistochemistry to detect viral RNA and proteins directly in tissue samples.In paper II, padlock probes were used to study the spatial gene expression of gene homologs from the X and Y chromosome in human embryonic nervous tissue. Furthermore, a strategy was devised to visualize and evaluate spatial expression patterns.The padlock probe-based approach for multiplexed spatial transcriptional profiling, in situ sequencing, was applied in paper III to study the regional and cell-type-specific dynamics of A-to-I RNA editing in the developing mouse brain.In paper IV, a technical characterization of padlock probes was performed with the aim of determining how to design a padlock probe to obtain optimal detection efficiency.The work in this thesis demonstrates the dramatic shift in how biological questions in cell and tissue biology can be addressed, enabled by the technological evolution of traditional in situ hybridization assays into high-throughput, multiplexed spatial transcription profiling.
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| 11. |
- Lundin, Elin, 1983-, et al.
(författare)
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Spatiotemporal mapping of RNA editing in the developing mouse brain using in situ sequencing reveals regional and cell-type-specific regulation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Adenosine-to-inosine (A-to-I) RNA editing is a process that contributes to the diversification of proteins that has been shown to be essential for neurotransmission and other neuronal functions. However, the spatiotemporal and diversification properties of RNA editing in the brain are largely unknown. Here, we applied in situ sequencing to distinguish between edited and unedited transcripts in distinct regions of the mouse brain at four developmental stages, and investigate the diversity of the RNA landscape.Results: We analyzed RNA editing at codon-altering sites using in situ sequencing at single-cell resolution, in combination with the detection of individual ADAR enzymes and specific cell type marker transcripts. This approach revealed cell-type specific regulation of RNA editing of a set of transcripts, and developmental and regional variation in editing levels for many of the targeted sites. We found increasing editing diversity throughout development, which arises through regional- and cell type-specific regulation of ADAR enzymes and target transcripts.Conclusions: Our single-cell in situ sequencing method has proved useful to study the complex landscape of RNA editing and our results indicate that this complexity arises due to distinct mechanisms of regulating individual RNA editing sites, acting both regionally and in specific cell types.
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| 12. |
- Nilsson, Elin, 1983, et al.
(författare)
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A novel polypeptide derived from human lactoferrin in sodium hyaluronate prevents postsurgical adhesion formation in the rat.
- 2009
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Ingår i: Annals of surgery. - 1528-1140. ; 250:6, s. 1021-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of the study was to evaluate whether a peptide derived from human lactoferrin, PXL01 could act safely to reduce the formation of peritoneal adhesions in the rat model and to map the molecular mechanisms of its action. SUMMARY BACKGROUND DATA: Adhesion formation is a significant problem within every surgical discipline causing suffering for the patients and major cost for the society. For many decades, attempts have been made to reduce postsurgical adhesions by reducing surgical trauma. It is now believed that major improvements in adhesion prevention will only be reached by developing dedicated antiscarring products, which are administrated in connection to the surgical intervention. METHODS: Anti-inflammatory as well as fibrinolytic activities of PXL01 were studied in relevant human cell lines. Using the sidewall defect-cecum abrasion model in the rat, the adhesion prevention properties of PXL01 formulated in sodium hyaluronate were evaluated. Large bowel anastomosis healing model in the rat was applied to study if PXL01 would have any negative effects on intestine healing. Results: PXL01 exhibits an inhibitory effect on the most important hallmarks of scar formation by reducing infections, prohibiting inflammation, and promoting fibrinolysis. PXL01 formulated in sodium hyaluronate markedly reduced formation of peritoneal adhesions in rat without any adverse effects on wound healing. CONCLUSIONS: A new class of synthetically derived water soluble low molecular weight peptide compound, PXL01 showed marked reduction of peritoneal adhesion formation in an animal model without any negative effects on healing. On the basis of these data, a comprehensive adhesion prevention regimen in clinical situation is expected.
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| 13. |
- Nilsson, Elin, 1983, et al.
(författare)
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Evoked thalamic neuronal activity following DRG application of two nucleus pulposus derived cell populations: an experimental study in rats.
- 2013
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Ingår i: European spine journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 22:5, s. 1113-1118
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the effects on evoked thalamic neuronal activity of application of notochordal cells and chondrocyte-like cells derived from nucleus pulposus (NP) onto a dorsal root ganglion (DRG) and to compare these effects with a previously reported increased thalamic activity induced by NP. METHODS: Nucleus pulposus was harvested from tail discs of adult rats and the disc cells were separated into two cell populations, notochordal cells and chondrocyte-like cells. The two cell populations were applied separately, or in combination, to the L4 DRG of anaesthetised female Sprague-Dawley rats during acute electrophysiological experiments. In control experiments, cell suspension medium was applied on the DRG. Recordings from the contralateral thalamus were sampled for 40min while electrically stimulating the ipsilateral sciatic nerve at above Aδ-fibre thresholds. RESULTS: Application of notochordal cells resulted in a decrease in evoked thalamic activity within 10min while chondrocyte-like cells did not induce any changes during the 40min of recording. The difference in evoked thalamic activity 40min after notochordal and chondrocyte-like cell application, respectively, was statistically significant. Neither an increased concentration of chondrocyte-like cells alone nor a combination of the two cell populations induced any changes in thalamic activity. CONCLUSIONS: Separate exposure of the DRG to the two NP-derived cell populations induced different effects on evoked thalamic activity, but none of the tested cell samples induced an increase in neuronal activity similar to that previously observed with NP. This indicates a high complexity of the interaction between NP and nervous tissue.
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| 14. |
- Nilsson, Elin, 1983, et al.
(författare)
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Mechanical compression and nucleus pulposus application on dorsal root Ganglia differentially modify evoked neuronal activity in the thalamus.
- 2013
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Ingår i: BioResearch open access. - : Mary Ann Liebert Inc. - 2164-7844 .- 2164-7860. ; 2:3, s. 192-8
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Tidskriftsartikel (refereegranskat)abstract
- A combination of mechanical compression caused by a protruding disc and leakage of nucleus pulposus (NP) from the disc core is presumed to contribute to intervertebral disc hernia-related pain. Experimental models of disc hernia including both components have resulted in changes in neuronal activity at the level of the dorsal root ganglion (DRG) and spinal cord, but changes within the brain have been less well studied. However, acute application of NP to a DRG without mechanical compression rapidly increases neuronal activity in the thalamus, a major brain relay nucleus processing information from sensory pathways including ascending nociceptive tracts. The combination of mechanical compression and NP might therefore result in further increases in central neuronal activity. Using an experimental disc herniation rat model including both mechanical compression and NP the present study aimed to investigate changes in neuronal activity in the contralateral thalamic ventral posterior lateral nucleus in vivo. Measurements were obtained while electrically stimulating the ipsilateral sciatic nerve at Aδ fiber intensities. The L4 DRG was subjected to light mechanical compression and NP exposure, and acute changes in evoked thalamic responses were recorded for up to 40min. In order to compare effects in naïve animals with effects following a longer period of NP exposure, animals that were either disc-punctured or sham-operated 24h previously were also included. In all animals, light mechanical compression of the DRG depressed the number of evoked neuronal responses. Prior NP exposure resulted in less potent changes following mechanical compression (80% of baseline) than that observed in naïve animals (50%). During the subsequent NP application, the number of evoked responses compared to baseline increased in pre-exposed animals (to 87%) as well as in naïve animals (72%) in which the removal of the mechanical compression resulted in a further increase (106%). The contribution of acute DRG compression and disc material leakage to changes in transmission in central neuronal networks is likely to be complex and to involve both short-term and long-term effects. Since a light mechanical compression may reduce transmission in nociceptive pathways, it is possible that the presence or absence of NP is crucial for pain development in the acute phase of disc herniation.
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| 15. |
- Nilsson, Elin, 1983
(författare)
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Neuronal networks involved in low back pain; experimental studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low back pain is a common cause of disability, with a lifetime prevalence of up to 80%. A lumbar disc herniation, involving a bulging disc and/or leakage of the intervertebral disc’s nucleus pulposus, may be a possible cause of back and sciatic pain. Low back pain has also been associated with dysfunctional control of the paraspinal muscles. The aim of this thesis was to study the neuronal networks involved in low back pain including sciatica. In paper I, the contribution of two descending tracts, the pyramidal tract and the reticulospinal tract to the activity of motoneurones innervating one of the muscles of the erector spinae (longissimus muscle) were investigated in the cat. In papers II and III, changes in evoked neuronal activity in the ventral posterior lateral (VPL) nucleus of the contralateral thalamus were investigated following an experimental disc herniation affecting the ipsilateral 4th lumbar (L4) dorsal root ganglion (DRG) in the rat. Paper II concerns the role of mechanical compression and application of nucleus pulposus to the DRG while paper III investigates the role of two individual cell populations of nucleus pulposus, notochordal and chondrocyte-like cells. The results in paper I show that central activation from pyramidal neurones to erector spinae muscle is primarily mediated via reticulospinal neurones, while a limited proportion is also mediated via interneurones activated by pyramidal tract neurones. In paper II, opposite effects on evoked neuronal activity in the VPL were found where the mechanical compression induced a decrease in neuronal activity and nucleus pulposus had a facilitating effect. In paper III, neither of the two cell populations of nucleus pulposus induced an increase in neuronal activity resembling the increase reported previously following application onto the DRG of whole nucleus pulposus tissue. This thesis investigates some of the complex neuronal networks likely to be involved in low back pain, both directly and indirectly. Insights gained from the use of animal models will contribute to our ultimate understanding of the complicated processes that operate during the establishment and maintenance of low back pain including sciatica.
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| 16. |
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| 17. |
- Nyström, Niklas, et al.
(författare)
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Human Enterovirus Species B in Ileocecal Crohn's Disease
- 2013
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Ingår i: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency ofNOD2mutations. Recent findings implicate a role ofNOD2and another CD susceptibility gene,ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.METHODS:We used immunohistochemistry andin situhybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.RESULTS:All patients with ICD had disease-associated polymorphisms inNOD2orATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.CONCLUSIONS:The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.
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| 18. |
- Olmarker, Kjell, 1958, et al.
(författare)
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Model for assessment of mobility of toes and healing of tendons in rabbits.
- 2010
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764 .- 2000-656X. ; 44:6, s. 266-71
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Forskningsöversikt (refereegranskat)abstract
- Repair of a transected flexor tendon will, despite careful technique and early rehabilitation, usually result in a restricted range of movement. This is mainly because adhesions form between the tendon and the surrounding structures. Our aim was to establish an experimental model in rabbits for future studies on new techniques to reduce the formation of adhesions after zone II repair of flexor tendons. In rabbits' hind paws the metatarsal bones II, IV, and V were removed and the flexor tendon was freed to the metatarsophalangeal (MTP) joint. The digits were secured in a specifically-designed biomechanical testing device comprising a servo-hydraulic actuator that was designed to apply controlled force or displacement. The tests were videotaped with a digital force-monitor behind the tested digit. Paper printouts from the recordings were obtained for 0, 0.5, 1, 2, 3, 4, and 5 Newton (N) and metatarsophalangeal, proximal interphalangeal, and distal interphalangeal, angles and distances between metatarsophalangeal joints and claws were measured. The tensile strength of the tendon was evaluated by a load-to-failure test. The continuous data obtained from the experiments were used to calculate functional stiffness at the selected forces. The model allows for unique continuous recordings of mobility of toes, thereby indirectly quantifying the presence of adhesions and the assessment of tensile strength. The data are reproducible, and there is little variation between the digits tested. The model is primarily intended to compare data among treated and non-treated digits of methods to limit the formation of adhesions after tendons have been repaired.
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| 19. |
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| 20. |
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| 21. |
- Onerup, Aron, 1983, et al.
(författare)
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Effects of a home-based exercise program on the insulin-like growth factor axis in patients operated for colorectal cancer in Sweden: Results from the randomised controlled trial PHYSSURG-C
- 2020
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 51, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We report results from a subgroup within the ongoing PHYSSURG-C trial with the aim to examine effects of exercise on IGF-1 and IGFBP-3 in patients undergoing colorectal cancer surgery. Design: Randomised controlled trial. Setting: A Swedish university hospital. Participants: Between 2015 and 2016, 217 patients were enrolled (I = 106, C = 111), with 122 patients that had given blood samples at baseline and at least at one follow-up (I = 51, C = 71). Patients 20 year or older with colorectal cancer were eligible. Exclusion criteria were emergency surgery, local surgery, language problems or inability to perform intervention. Interventions: Patients were computer-randomised to either a daily home-based aerobic exercise intervention (I), or to usual care (C). The intervention lasted two weeks before surgery and four weeks after discharge from hospital and consisted of medium-intensity aerobic exercise and inspiratory muscle training. Circulating concentrations of IGF-1 and IGFBP-3 were determined by blinded personnel at baseline, time of surgery and 4–6 weeks postoperatively. Primary and secondary outcome measures: The outcome of this subpopulation report was change in IGF-1/IGFBP-3 ratio, IGF-1 and IGFBP-3 concentrations from baseline to surgery, and 4–6 weeks postoperatively. Results: The IGF-1/IGFBP-3 ratio increased from baseline to surgery by 11% in I and 8% in C with no difference between groups (I vs. C: 1.04, 95%CI: 0.97–1.11; p = 1.000). Postoperative change was 5% in I and 3% in C with no difference between groups (I vs. C:1.03, 95%CI: 0.96–1.10; p = 1.000). Results concerning IGF-1 and IGFBP-3 also showed statistically significant dynamics over time with no difference between groups. No adverse events were reported. Conclusions: The home-based exercise program in our trial did not have any effect on IGF-1, or IGFBP-3. Trial registration: The study was registered at ClinicalTrials.gov with identifier NCT02299596. This work was funded externally.
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| 22. |
- Onerup, Aron, 1983, et al.
(författare)
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The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): Study protocol for a randomised controlled trial
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Author(s).Background: Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer. Methods/design: We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis. Discussion: An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results. Trial registration: ClinicalTrials.gov identifier: NCT02299596. Registered on 17 November 2014.
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| 23. |
- Ronnberg, Elin, et al.
(författare)
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Analysis of human lung mast cells by single cell RNA sequencing
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells are tissue-resident cells playing major roles in homeostasis and disease conditions. Lung mast cells are particularly important in airway inflammatory diseases such as asthma. Human mast cells are classically divided into the subsets MCT and MCTC, where MCT express the mast cell protease tryptase and MCTC in addition express chymase, carboxypeptidase A3 (CPA3) and cathepsin G. Apart from the disctintion of the MCT and MCTC subsets, little is known about the heterogeniety of human lung mast cells and a deep analysis of their heterogeniety has previously not been performed. We therefore performed single cell RNA sequencing on sorted human lung mast cells using SmartSeq2. The mast cells showed high expression of classical mast cell markers. The expression of several individual genes varied considerably among the cells, however, no subpopulations were detected by unbiased clustering. Variable genes included the protease-encoding transcripts CMA1 (chymase) and CTSG (cathepsin G). Human lung mast cells are predominantly of the MCT subset and consistent with this, the expression of CMA1 was only detectable in a small proportion of the cells, and correlated moderately to CTSG. However, in contrast to established data for the protein, CPA3 mRNA was high in all cells and the correlation of CPA3 to CMA1 was weak.
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| 24. |
- Schoultz, Elin, et al.
(författare)
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Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor
- 2023
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Ingår i: ISCIENCE. - 2589-0042. ; 26:7
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Tidskriftsartikel (refereegranskat)abstract
- Cells of origin in cancer determine tumor phenotypes, but whether lineage-defining transcription factors might influence tissue specificity of tumorigenesis among organs with similar developmental traits are unknown. We demonstrate here that tumor development and progression markedly differ in lung and thyroid targeted by Braf mutation in Nkx2.1CreER(T2) mice heterozygous for Nkx2-1. In absence of tamoxifen, non-induced Nkx2.1CreER(T2);Braf(CA/+) mutants developed multiple full-blown lung adenocarcinomas with a latency of 1-3 months whereas thyroid tumors were rare and constrained, although minute Braf(CA) activation documented by variant allele sequencing was similar in both tissues. Induced oncogene activation accelerated neoplastic growth only in the lungs. By contrast, NKX2-1(+) progenitor cells were equally responsive to constitutive expression of mutant Braf during lung and thyroid development. Both lung and thyroid cells transiently downregulated NKX2-1 in early tumor stages. These results indicate that BRAF(V600E)-induced tumorigenesis obey organ-specific traits that might be differentially modified by a shared lineage factor.
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| 25. |
- Shrestha, Sony Shakya, et al.
(författare)
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Excitatory inputs to four types of spinocerebellar tract neurons in the cat and the rat thoraco-lumbar spinal cord.
- 2012
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Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 590:Pt 7, s. 1737-55
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Tidskriftsartikel (refereegranskat)abstract
- The cerebellum receives information from the hindlimbs through several populations of spinocerebellar tract neurons. Although the role of these neurons has been established in electrophysiological experiments, the relative contribution of afferent fibres and central neurons to their excitatory input has only been estimated approximately so far. Taking advantage of differences in the immunohistochemistry of glutamatergic terminals of peripheral afferents and of central neurons (with vesicular glutamate transporters VGLUT1 or VGLUT2, respectively), we compared sources of excitatory input to four populations of spinocerebellar neurons in the thoraco-lumbar spinal cord: dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and in the dorsal horn (dhDSCT) and ventral spinocerebellar tract (VSCT) neurons including spinal border (SB) neurons. This was done on 22 electrophysiologically identified intracellularly labelled neurons in cats and on 80 neurons labelled by retrograde transport of cholera toxin b subunit injected into the cerebellum of rats. In both species distribution of antibodies against VGLUT1 and VGLUT2 on SB neurons (which have dominating inhibitory input from limb muscles), revealed very few VGLUT1 contacts and remarkably high numbers of VGLUT2 contacts. In VSCT neurons with excitatory afferent input, the number of VGLUT1 contacts was relatively high although VGLUT2 contacts likewise dominated, while the proportions of VGLUT1 and VGLUT2 immunoreactive terminals were the reverse on the two populations of DSCT neurons. These findings provide morphological evidence that SB neurons principally receive excitatory inputs from central neurons and provide the cerebellum with information regarding central neuronal activity.
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| 26. |
- Wiig, M., et al.
(författare)
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A lactoferrin-derived peptide (PXL01) for the reduction of adhesion formation in flexor tendon surgery: an experimental study in rabbits
- 2011
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Ingår i: J Hand Surg Eur Vol. - : SAGE Publications. - 2043-6289 .- 1753-1934. ; 36:8, s. 656-62
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Tidskriftsartikel (refereegranskat)abstract
- Injuries to flexor tendons can lead to loss of finger function after healing due to adhesion formation. The aim of this study was to assess the efficacy and safety of the new peptide, PXL01, in the prevention of peritendinous adhesions. The effect of a single intraoperative administration of PXL01 in sodium hyaluronate on mobility of the affected digit after surgery was assessed in a rabbit model by measuring total active motion, metatarsophalangeal-claw distance and resistance to bending the digits. Load-to-failure testing was done in the same specimens to assess tendon healing. The results demonstrated that a single application of PXL01 in sodium hyaluronate significantly improved mobility of the treated digits compared with the digits in which the same surgery was carried out but no treatment was provided. No negative effects on tendon healing were observed in connection with the treatment.
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