| 1. |
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| 2. |
- Hansson, EM, et al.
(author)
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Control of Notch-ligand endocytosis by ligand-receptor interaction
- 2010
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In: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 123:17Pt 17, s. 2931-2942
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Journal article (peer-reviewed)abstract
- In Notch signaling, cell-bound ligands activate Notch receptors on juxtaposed cells, but the relationship between ligand endocytosis, ubiquitylation and ligand-receptor interaction remains poorly understood. To study the specific role of ligand-receptor interaction, we identified a missense mutant of the Notch ligand Jagged1 (Nodder, Ndr) that failed to interact with Notch receptors, but retained a cellular distribution that was similar to wild-type Jagged1 (Jagged1WT) in the absence of active Notch signaling. Both Jagged1WT and Jagged1Ndr interacted with the E3 ubiquitin ligase Mind bomb, but only Jagged1WT showed enhanced ubiquitylation after co-culture with cells expressing Notch receptor. Cells expressing Jagged1WT, but not Jagged1Ndr, trans-endocytosed the Notch extracellular domain (NECD) into the ligand-expressing cell, and NECD colocalized with Jagged1WT in early endosomes, multivesicular bodies and lysosomes, suggesting that NECD is routed through the endocytic degradation pathway. When coexpressed in the same cell, Jagged1Ndr did not exert a dominant-negative effect over Jagged1WT in terms of receptor activation. Finally, in Jag1Ndr/Ndr mice, the ligand was largely accumulated at the cell surface, indicating that engagement of the Notch receptor is important for ligand internalization in vivo. In conclusion, the interaction-dead Jagged1Ndr ligand provides new insights into the specific role of receptor-ligand interaction in the intracellular trafficking of Notch ligands.
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| 3. |
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| 4. |
- Marklund, U, et al.
(author)
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Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression
- 2010
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In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 137:3, s. 437-445
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Journal article (peer-reviewed)abstract
- Homeodomain (HD) transcription factors and components of the Notch pathway [Delta1 (Dll1), Jagged1 (Jag1) and the Fringe (Fng) proteins] are expressed in distinct progenitor domains along the dorsoventral (DV) axis of the developing spinal cord. However, the internal relationship between these two regulatory pathways has not been established. In this report we show that HD proteins act upstream of Notch signalling. Thus, HD proteins control the spatial distribution of Notch ligands and Fng proteins, whereas perturbation of the Notch pathway does not affect the regional expression of HD proteins. Loss of Dll1 or Jag1 leads to a domain-specific increase of neuronal differentiation but does not affect the establishment of progenitor domain boundaries. Moreover, gain-of-function experiments indicate that the ability of Dll1 and Jag1 to activate Notch is limited to progenitors endogenously expressing the respective ligand. Fng proteins enhance Dll1-activated Notch signalling and block Notch activation mediated by Jag1. This finding, combined with the overlapping expression of Fng with Dll1 but not with Jag1, is likely to explain the domain-specific activity of the Notch ligands. This outcome is opposite to the local regulation of Notch activity in most other systems, including the Drosophila wing, where Fng co-localizes with Jagged/Serrate rather than Dll/Delta, which facilitates Notch signalling at regional boundaries instead of within domains. The regulation of Notch activation in the spinal cord therefore appears to endow specific progenitor populations with a domain-wide autonomy in the control of neurogenesis and prevents any inadequate activation of Notch across progenitor domain boundaries.
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| 5. |
- Trieu, K, et al.
(author)
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Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis
- 2021
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In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 18:9, s. e1003763-
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Journal article (peer-reviewed)abstract
- We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], andtrans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality.Methods and findingsWe measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose–response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93,P= 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case–cohort, or nested case–control studies, higher 15:0 and 17:0 but nott16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels.ConclusionsIn a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.
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| 6. |
- Baunsgaard, C. B., et al.
(author)
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EXOSKELETON GAIT TRAINING AFTER SPINAL CORD INJURY: AN EXPLORATORY STUDY ON SECONDARY HEALTH CONDITIONS
- 2018
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In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 50:9, s. 806-813
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Journal article (peer-reviewed)abstract
- Objective: To explore changes in pain, spasticity, range of motion, activities of daily living, bowel and lower urinary tract function and quality of life of individuals with spinal cord injury following robotic exoskeleton gait training. Methods: Three training sessions per week for 8 weeks using an Ekso GT robotic exoskeleton (Ekso Bionics). Included were individuals with recent (<1 year) or chronic (>1 year) injury, paraplegia and tetraplegia, complete and incomplete injury, men and women. Results: Fifty-two participants completed the training protocol. Pain was reported by 52% of participants during the week prior to training and 17% during training, but no change occurred longitudinally. Spasticity decreased after a training session compared with before the training session (p< 0.001), but not longitudinally. Chronically injured participants increased Spinal Cord Independence Measure (SCIM III) from 73 to 74 (p= 0.008) and improved life satisfaction (p= 0.036) over 8 weeks of training. Recently injured participants increased SCIM III from 62 to 70 (p<0.001), but no significant change occurred in life satisfaction. Range of motion, bowel and lower urinary function did not change over time. Conclusion: Training seemed not to provoke new pain. Spasticity decreased after a single training session. SCIM III and quality of life increased longitudinally for subsets of participants.
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| 7. |
- Brattsand, G, et al.
(author)
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Quantitative analysis of the expression and regulation of an activation-regulated phosphoprotein (oncoprotein 18) in normal and neoplastic cells.
- 1993
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In: Leukemia. - 0887-6924 .- 1476-5551. ; 7:4, s. 569-79
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Journal article (peer-reviewed)abstract
- Activation of protein kinase C results in phosphorylation of a 19-kDa protein termed 19K. Isolation and sequence analysis of a cDNA encoding the 19K protein revealed that this protein has been studied in other systems under different names. The name oncoprotein 18 (Op18) has been proposed on the basis of a postulated up-regulation in neoplastic cells. In the present report we adopt the designation Op18 for the 19K protein, and quantify this phosphoprotein in a series of leukemia/lymphoma cell lines, a panel of non-transformed cells and some terminally differentiated cell types. For this purpose we have developed reagents allowing quantitative Western-blot analysis, and quantification of Op18 on the single cell level by flow cytometric analysis. The data demonstrates a pronounced up-regulation of the Op18 protein in most leukemia/lymphoma cell lines. The HPB-ALL cell line provided the most extreme case and expressed 7 x 10(6) Op18 molecules/cell, which compares with 0.65 x 10(6) Op18 molecules/cell in non-transformed lymphoblastoid cells. The expression of Op18 appears to be restricted to cell types with proliferative potential, but it is clear from our results that up-regulation of Op18 is uncoupled from cellular proliferation. Moreover, by employing an Epstein-Barr virus based shuttle vector, we expressed Op18 cDNA in lymphoblastoid cells. This resulted in a three to fourfold up-regulation of Op18 that did not have any detectable consequences for cell-surface phenotype or cell size. However, increased expression of Op18 resulted in a partial inhibition of cell proliferation. Taken altogether, the results suggest that up-regulation Op18 levels in leukemia/lymphoma cells are strongly associated with, but not a direct cause of tumour progression.
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| 9. |
- Carlbring, Per, et al.
(author)
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Treat your social anxiety disorder with this gamified smartphone app
- 2016
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Conference paper (peer-reviewed)abstract
- Aim: Social anxiety disorder (SAD) is a common debilitating mental illness with large negative effects on quality of life and economic productivity. Modern psychotherapy treatments utilizing cognitive–behavioral theory are increasingly delivered over the Internet and more recently using smartphone applications. The Challenger App written natively for the Apple iPhone was developed at the Stockholm University Department of Psychology for the treatment of SAD and uses a number of advanced features not previously seen in past mental health applications; these include real-time location awareness, notifications, anonymous social interaction between users, a high-degree of personalization and use of gamification techniques.Method: A total of 209 participants with a primary diagnosis of SAD were randomized to one of three groups: 1) Self-help book, 2) Self-help book + the Challenger app, or 3) waitlist. The treatment period lasted 6 weeks. Primary outcome measure was Liebowitz Social Anxiety Scale self- report (LSAS-SR). Also included where the Quality of Life Inventory, Patient Health Questionnaire, and the Generalized Anxiety Disorder-7 (GAD-7). Outcome was analyzed according to the intention to treat principle.Results: Both treatment groups were superior to the waitlist. On the main outcome measure (LSAS-SR) the effect size for the waitlist was Cohens d=0.14. The group that received the self-help book with the addition of the Challenger app was significantly superior (d=1.0) to just reading the self- help book (d=0.61). Participants requited by way of Newspaper advertisement were more likely to reach high end-state functioning (OR=4.1) and the same was true for participants without prior psychological treatment history as compared with having a previous experience (OR=4.4).Conclusion: Adding the smartphone app is a cost effective way of improving the outcome when treating SAD with a self-help book.
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| 11. |
- Dahlgren, Hanna, et al.
(author)
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Energy and flux variations across thin auroral arcs
- 2011
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In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 29:10, s. 1699-1712
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Journal article (peer-reviewed)abstract
- Two discrete auroral arc filaments, with widths of less than 1 km, have been analysed using multi-station, multi-monochromatic optical observations from small and medium field-of-view imagers and the EISCAT radar. The energy and flux of the precipitating electrons, volume emission rates and local electric fields in the ionosphere have been determined at high temporal (up to 30 Hz) and spatial (down to tens of metres) resolution. A new time-dependent inversion model is used to derive energy spectra from EISCAT electron density profiles. The energy and flux are also derived independently from optical emissions combined with ion-chemistry modelling, and a good agreement is found. A robust method to obtain detailed 2-D maps of the average energy and number flux of small scale aurora is presented. The arcs are stretched in the north-south direction, and the lowest energies are found on the western, leading edges of the arcs. The large ionospheric electric fields (250 mV m(-1)) found from tristatic radar measurements are evidence of strong currents associated with the region close to the optical arcs. The different data sets indicate that the arcs appear on the boundaries between regions with different average energy of diffuse precipitation, caused by pitch-angle scattering. The two thin arcs on these boundaries are found to be related to an increase in number flux (and thus increased energy flux) without an increase in energy.
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| 19. |
- Jansson, S. -A, et al.
(author)
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Socioeconomic evaluation of well-characterized allergy to staple foods in adults
- 2014
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 69:9, s. 1241-1247
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Journal article (peer-reviewed)abstract
- Background: The aim of the present study was to evaluate if total, direct, indirect, and intangible costs differ between a cohort of adults with well-characterized allergy to staple foods ('cases') and controls. Methods: Swedish adults with objectively diagnosed food allergy to cow's milk, hen's egg, and/or wheat were recruited at an outpatient allergy clinic. Controls age- and sex-matched to cases were recruited from the same geographic area. For assessing the household costs of food allergy, a disease-specific socioeconomic questionnaire, developed within EuroPrevall, was utilized. Results: Overall annual total costs at the household level were significantly higher among adults with food allergy compared with controls (the difference amounted to 8164 (sic) ), whereas direct costs did not differ between cases and controls. However, household healthcare costs and costs for medicines were significantly higher for cases vs controls. Furthermore, indirect costs were significantly higher for households with food-allergic adults vs households without food-allergic adults. Specifically, more time was spent on performing domestic tasks due to a family member's food-allergy-related illness, as well as shopping and preparing food, and seeking food-allergy-related information. Presence of food allergy also affected intangible costs. Adults with food allergy experienced overall lower health status compared with controls. Conclusions: Swedish adults with allergy to staple foods have higher total costs determined as direct, indirect, and intangible costs using the disease-specific socioeconomic questionnaire. Thus, total costs were 8164 (sic) higher per year in households with at least one adult allergic to staple foods compared with controls.
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| 24. |
- Laguzzi, F., et al.
(author)
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Circulating fatty acids in relation to alcohol consumption : Cross-sectional results from a cohort of 60-year-old men and women
- 2018
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In: Clinical Nutrition. - : CHURCHILL LIVINGSTONE. - 0261-5614 .- 1532-1983. ; 37:6, Part A, s. 2001-2010
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Journal article (peer-reviewed)abstract
- Background & aims: Alcohol consumption is considered to affect circulating fatty acids (FAs) but knowledge about specific associations is limited. We aimed to assess the relation between alcohol consumption and serum FAs in 60-year-old Swedish men and women.Methods: In a random sample of 1917 men and 2058 women residing in Stockholm county, cross-sectional associations between different categories of alcohol consumption and FAs were assessed using linear regression; beta(1) coefficients with 95% confidence interval (Cl) were calculated. Self-reported alcohol consumption was categorized as none, low (<= 9.9 g/day) (reference), moderate (10-29.9 g/day) and high (>= 30 g/day). Moderate alcohol consumption was further subdivided into consumption of beer, wine, liquor and their combinations. Thirteen serum cholesterol ester FM were measured by gas chromatography and individual FM were expressed as percentage of total FAs.Results: Increasing alcohol consumption was associated to linear increase of saturated myristic acid, monounsaturated FAs and n-6 polyunsaturated (PUFA) arachidonic acid, whereas linear decrease was noted for saturated pentadecanoic acid and for n-6 PUFA linoleic acid. With non-linear associations, increasing alcohol consumption also associated to decreased saturated stearic acid, n-6 PUFA dihomogamma-linolenic acid, and n-3 PUFA docosahexaenoic acid and increased saturated palmitic acid, n-6 PUFA gamma-linolenic acid and n-3 PUFA eicosapentaenoic acid. Among types of beverages, wine consumption was associated with n-6 PUFA arachidonic acid (beta(1) 0.59; 95% CI: 030;0.88) and the n-3 PUFAs eicosapentaenoic acid (beta(1) 0.54; 95% CI: 0.30;0.78), and docosahexaenoic acid (beta(1) 0.06; 95% CI: 0.00;0.12).Conclusions: These findings may give important basis for further investigations to better understand biological mechanisms behind the dose-dependent associations between alcohol consumption and health outcomes observed in many previous studies.
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| 25. |
- Laguzzi, F., et al.
(author)
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Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease : Pooled De Novo Results From 15 Observational Studies
- 2024
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In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 149:4, s. 305-316
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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| 28. |
- Lek, M, et al.
(author)
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A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning
- 2010
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In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 137:23, s. 4051-4060
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Journal article (peer-reviewed)abstract
- The deployment of morphogen gradients is a core strategy to establish cell diversity in developing tissues, but little is known about how small differences in the concentration of extracellular signals are translated into robust patterning output in responding cells. We have examined the activity of homeodomain proteins, which are presumed to operate downstream of graded Shh signaling in neural patterning, and describe a feedback circuit between the Shh pathway and homeodomain transcription factors that establishes non-graded regulation of Shh signaling activity. Nkx2 proteins intrinsically strengthen Shh responses in a feed-forward amplification and are required for ventral floor plate and p3 progenitor fates. Conversely, Pax6 has an opposing function to antagonize Shh signaling, which provides intrinsic resistance to Shh responses and is important to constrain the inductive capacity of the Shh gradient over time. Our data further suggest that patterning of floor plate cells and p3 progenitors is gated by a temporal switch in neuronal potential, rather than by different Shh concentrations. These data establish that dynamic, non-graded changes in responding cells are essential for Shh morphogen interpretation, and provide a rationale to explain mechanistically the phenomenon of cellular memory of morphogen exposure.
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| 36. |
- Marklund, Björn, et al.
(author)
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Retention Footprint : Visualising and monitoring student retention in study programmes across Europe
- 2012
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In: Proceedings of the 40th SEFI Annual Conference 2012 - Engineering Education 2020. - : European Society for Engineering Education (SEFI). - 9782873520052
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Conference paper (peer-reviewed)abstract
- Most of the universities across Europe have their own way of measuring and monitoring student progression, retention, attrition, drop out, etc. The way of holding statistics and calculating indicators differs as well as the demands of different stakeholders within the universities and society. ATTRACT (Enhance the Attractiveness of Studies in Science and Technology) is a European Commission supported project aiming to increase knowledge and inform practice about student recruitment and retention in engineering and technology education. Within this project partners agreed to test and evaluate a method of visualising and monitoring student retention in a so-called footprint in selected fields of programmes. The tool was originally developed in the Swedish project "Ung Ingenjör" http://www.kth.se/unging The test had three sub aims: 1. The overall level was to test if the visualising method can be used to compare/benchmark engineering education in Europe concerning retention. 2. The next level was to test and evaluate how the method can be used in assessing engineering education. 3. The final level aimed to test if the method can be used to compare different student groups concerning study background coupled to retention. The footprint itself can only be an indicator as such and the reasons behind study progress, drop out, low graduation rate etc. can only be found through further quantitative and qualitative analysis and discussions. The results from this exercise show the complexity of finding reasons and proper actions. The results also show that the way of monitoring facts and figures in a visual presentation trigs the viewer to dig deeper and do further analysis.
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| 40. |
- Marklund, U, et al.
(author)
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Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase.
- 1993
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 268:20
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Journal article (peer-reviewed)abstract
- Oncoprotein 18 (Op18) is an 18-19-kDa cytoplasmic phosphoprotein, of unknown function, that is frequently up-regulated in transformed cells. Stimulation of various cell-surface receptors results in extensive phosphorylation of Op18 and this protein has, therefore, previously been implicated in intracellular signaling. In the present study, by expression of specific Op18 cDNA mutant constructs and phosphopeptide mapping, we have identified in vivo phosphorylation sites. In conjunction with in vitro phosphorylation experiments, using purified wild-type and mutant Op18 proteins in combination with a series of kinases, these results have identified two distinct proline-directed kinase families that phosphorylate Op18 with overlapping but distinct site preference. These two kinase families, mitogen activated protein (MAP) kinases and cyclin dependent cdc2 kinases, are involved in receptor and cell cycle-regulated phosphorylation events, respectively. Therefore, Op18 may reside at a junction where receptor and cell cycle-regulated kinase families interact with the same substrate. The present study shows that the MAP kinase has a 20-fold preference for Ser25 as opposed to Ser38 of Op18, while cdc2 kinases have a 5-fold preference for the Ser38 residue. Only a minor fraction of the 4.5 x 10(6) Op18 molecules/cell in a leukemic T-cell line are normally in their Ser25 phosphorylated form. However, antigen receptor stimulation of this cell line is shown to result in a rapid conversion of 35-45% of all Op18 molecules to the Ser25 phosphorylated form. These results suggest that Ser25 of Op18 may be a major cytoplasmic target for the MAP kinase in cells with high expression of Op18.
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