| 1. |
- Almandoz-Gil, Leire, et al.
(författare)
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In situ proximity ligation assay reveals co-localization of alpha-synuclein and SNARE proteins in murine primary neurons
- 2018
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of alpha-synuclein (alpha Syn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of aSyn is to promote the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between aSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human aSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human aSyn, a PLA signal indicating close proximity between aSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human aSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of aSyn and the SNARE proteins in primary neuronal cultures
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| 2. |
- Gustafsson, Sofia, et al.
(författare)
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Intact blood-brain barrier transport of small molecular drugs in animal models of amyloid beta and alpha-synuclein pathology
- 2018
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Ingår i: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 128, s. 482-491
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Tidskriftsartikel (refereegranskat)abstract
- Pathophysiological impairment of the neurovascular unit, including the integrity and dynamics of the blood-brain barrier (BBB), has been denoted both a cause and consequence of neurodegenerative diseases. Pathological impact on BBB drug delivery has also been debated. The aim of the present study was to investigate BBB drug transport, by determining the unbound brain-to-plasma concentration ratio (K-p,K-uu,K-brain), in aged A beta PP-transgenic mice, alpha-synuclein transgenic mice, and wild type mice. Mice were dosed with a cassette of five compounds, including digoxin, levofloxacin (1 mg/kg, s.c.), paliperidone, oxycodone, and diazepam (0.25 mg/kg, s.c.). Brain and blood were collected at 0.5,1, or 3 h after dosage. Drug concentrations were measured using LC-MS/MS. The total brain-to-plasma concentration ratio was calculated and equilibrium dialysis was used to determine the fraction of unbound drug in brain and plasma for all compounds. Together, these three measures were used to determine the Kp,uu,brain value. Despite A beta or alpha-synuclein pathology in the current animal models, no difference was observed in the extent of drug transport across the BBB compared to wild type animals for any of the compounds investigated. Hence, the present study shows that the concept of a leaking barrier within neurodegenerative conditions has to be interpreted with caution when estimating drug transport into the brain. The capability of the highly dynamic BBB to regulate brain drug exposure still seems to be intact despite the presence of pathology. (C) 2017 The Authors. Published by Elsevier Ltd.
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| 3. |
- Hörberg, Anna, et al.
(författare)
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Treat me nice! -a cross-sectional study examining support during the first year in the emergency medical services
- 2018
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Background Working in the emergency medical service (EMS) can be extremely varying and sometimes physically and psychologically demanding. Being new in this context can be a great challenge. This study aim to describe what ambulance nurses consider to be important support during the first year in the EMS.Methods Three hundred and eighty-nine eligible participants that had graduated from the prehospital emergency care program were identified via university registrations office in Sweden. The eligible participants received a study specific questionnaire via mail consisting of 70 statements about support during the first year. The perceived importance of each statement were graded on a 7-point Likert scale. The gradings were analysed using descriptive statistics and frequencies, mean and SD were calculated.Results Two hundred and thirty questionnaires were returned fully completed, giving a response rate of 59%. Fourteen statements regarding desirable support were rated with mean values >6.00 and SD<1.00 and considered as being the most important during the first year in the EMS. The important supports regarded; colleagues and work environment, management and organisation, experience-based knowledge, introduction period, practical support, and theoretical support. Most statements regarded culture and climate and the way the newcomers wanted to be treated.Conclusion It was concluded that an important way to support newcomers in the EMS is to treat them nice'. This can be achieved by creating an open climate and a welcoming culture where the new professionals feel trusted and treated with respect, created ways to work structurally, have applicable medical guidelines, and for newcomers to receive feedback on their actions.
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| 4. |
- Lindström, Veronica, 1966-
(författare)
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Linkages between attributes of SME:s and manufacturing performance measures
- 2018
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Ingår i: Preprints of 20th International Working Seminar on Production Economics. - Linköping. ; , s. 285-296
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Konferensbidrag (refereegranskat)abstract
- In the strategic planning of manufacturing, companies should assess their competitive advantage with the means of performance measures (PMs) and achieve a consistency with the decision making. The literature on PMs shows that there are mainly two views of PM development. The first view is the PM diversity view which highlights the importance of using a wide set of PMs. The other view is PM alignment, which advocates the alignment between PMs and manufacturing strategy. Although the rich literature on PMs, research on PMs in Small- and Medium sized enterprises (SMEs) is limited but shows that the use of PMs in SMEs is typically financially focused, informal, and unstructured. The use of this approach in SMEs is likely to hinder the achievement of strategic objectives. This paper contributes to the research of PMs in manufacturing SMEs by analysing the relationships between the use of PMs and certain attributes of the SME. The used approach is multiple case study for exploring linkages between PM diversity and alignment with the manufacturing strategy and firm context. The data collection of each SME includes several strategic manufacturing attributes such as type of production system, manufacturing capabilities, and no. of PMs and specific measurements. The findings indicate a strong relationship between PM diversity and firm turnover, whereas the relationship seems weak between PM diversity and manufacturing capability. Furthermore, the relationship between PM alignment and competitive priorities indicate no alignment for SMEs, whereas the alignment between production system and competitive priorities seems to be stronger.
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