| 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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