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- Edvinsson, Jacob Carl Alexander, et al.
(författare)
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Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
- 2020
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:12, s. 1296-1309
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.
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| 2. |
- Bergman, Maria, 1981-
(författare)
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Constructing communities : The establishment and demographic development of sawmill communities in the Sundsvall district, 1850-1890
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation studies the establishment and demographic development of the sawmill communities that emerged in the Sundsvall district during the latter half of the 19th century. The intention is to highlight the importance of the sawmill communities and their resident populations by discussing community construction from a demographic perspective as well as socially and symbolically. Based on church registers, this is a longitudinal study that includes information from 31 individual sawmill communities. This study has shown that the establishment and demographic development of the sawmill communities was not an instant process that necessarily followed the construction of the sawmill industries. The prerequisites of the geographical locations and year of establishment influenced population development, but the speed and size of the settlements were individual to each mill site. More prosperous times for the industry during the 1870s resulted in that migration increased consequently leading to quickly populated communities and larger registered core populations in residence. Migration to the sawmill communities from within the parishes was infrequent and the geographical backgrounds revealed that an extremely small proportion of the populations had been born within the district, implying a migratory hesitation among locally born. The sawmill populations were male-dominated due to the large groups of temporary workers inhabiting the communities, although, adult males barely made up one-third of the registered populations. The largest demographic group was children aged 0-14 years. The strong presence of children and high proportions of married individuals suggests that the sawmill communities were family oriented communities, more so than non-sawmill areas. Long-time settled families had usually formed kinship networks with other residents. This dissertation concludes that while time was important for the development of the sawmill communities, so were the registered populations residing in these communities. Residency would have been key in claiming belonging to the sawmill communities and to be considered as a real sawmill worker. Residency, family and kin therefore contributed to the construction of community structures, geographically, socially and symbolically.
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| 7. |
- Bjärntoft, Sofie, et al.
(författare)
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A participatory approach to identify key areas for sustainable work environment and health in employees with flexible work arrangements
- 2021
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 13:24
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Tidskriftsartikel (refereegranskat)abstract
- Flexible work arrangements are common worldwide, but knowledge on how to achieve a sustainable work environment is sparse. The aim of this study was to use a participatory approach to identify concrete suggestions and key areas for improvement that were considered relevant, effective, and feasible for promoting good work environment and health at organizational, work group and individual level (O-G-I), among office employees with flexible work arrangements. Eight focus group interviews (including 45 employees) were conducted in a large Swedish government agency in 2017. By using a Tree diagram approach, employees made a total of 279 suggestions for improvements, which were sorted into O-G-I levels and mapped into 18 key areas. We found that 13 key areas addressed organizational level (e.g., improving leadership, policy, job demands, and work efficiency), two key areas addressed group level (create common rules of availability and activity-based working), and three key areas addressed individual level (e.g., individuals’ responsibility to clearly communicate their availability). The participatory process was effective in obtaining concrete suggestions and key areas in need of improvement, which may provide an action plan that can guide organizations in developing interventions to promote good work environment and health in flexible work.
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| 8. |
- Bömers, Jesper Peter, et al.
(författare)
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The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats
- 2022
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- Aneurysmal subarachnoid haemorrhage (SAH) is a haemorrhagic stroke that causes approximately 5% of all stroke incidents. We have been working on a treatment strategy that targets changes in cerebrovascular contractile receptors, by blocking the MEK/ERK1/2 signalling pathway. Recently, a positive effect of trametinib was found in male rats, but investigations of both sexes in pre-clinical studies are an important necessity. In the current study, a SAH was induced in female rats, by autologous blood-injection into the pre-chiasmatic cistern. This produces a dramatic, transient increase in intracranial pressure (ICP) and an acute and prolonged decrease in cerebral blood flow. Rats were then treated with either vehicle or three doses of 0.5 mg/kg trametinib (specific MEK/ERK1/2 inhibitor) intraperitoneally at 3, 9, and 24 h after the SAH. The outcome was assessed by a panel of tests, including intracranial pressure (ICP), sensorimotor tests, a neurological outcome score, and myography. We observed a significant difference in arterial contractility and a reduction in subacute increases in ICP when the rats were treated with trametinib. The sensory motor and neurological outcomes in trametinib-treated rats were significantly improved, suggesting that the improved outcome in females is similar to that of males treated with trametinib.
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| 9. |
- Chorell, Erik, 1980-, et al.
(författare)
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Design and synthesis of C-2 substituted Thiazolo and Dihydrothiazolo ring-fused 2-Pyridones : pilicides with increased antivirulence activity
- 2010
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Ingår i: Journal of Medicinal Chemistry. - Washington, USA : American Chemical Society. - 0022-2623 .- 1520-4804. ; 53:15, s. 5690-5695
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Tidskriftsartikel (refereegranskat)abstract
- Pilicides block pili formation by binding to pilus chaperones and blocking their function in the chaperone/usher pathway in E. coli. Various C-2 substituents were introduced on the pilicide scaffold by design and synthetic method developments. Experimental evaluation showed that proper substitution of this position affected the biological activity of the compound. Aryl substituents resulted in pilicides with significantly increased potencies as measured in pili-dependent biofilm and hemagglutination assays. The structural basis of the PapD chaperone-pilicide interactions was determined by X-ray crystallography.
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| 10. |
- Chorell, Erik, et al.
(författare)
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Design and Synthesis of Fluorescent Pilicides and Curlicides : Bioactive Tools to Study Bacterial Virulence Mechanisms
- 2012
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Ingår i: Chemistry - A European Journal. - Berlin : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 18:15, s. 4522-4532
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Tidskriftsartikel (refereegranskat)abstract
- Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores. Several of the resulting fluorescent compounds had improved activities as measured in pili- and curli-dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated with the bacteria with a heterogeneous distribution.
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