| 11. |
- Chen, Yan, et al.
(författare)
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The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study
- 2019
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 43:4, s. 808-820
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. Methods: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. Results: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. Conclusions: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.
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| 12. |
- Crema, Andrea, et al.
(författare)
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Helping Hand grasp rehabilitation : Preliminary assessment on chronic stroke patients
- 2017
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Ingår i: 8th International IEEE EMBS Conference on Neural Engineering, NER 2017. - 9781538619162 ; , s. 146-149
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Konferensbidrag (refereegranskat)abstract
- The Helping Hand (HH) system is a novel grasp rehabilitation platform aimed at simplifying the clinical usage of wearable electrode arrays for neuromuscular electrical stimulation (NMES). In a randomized dose-matched, clinical study we evaluate usability and effectiveness of the HH treatment, and of other enriched upper limb rehabilitation treatments, and compare the outcomes. This paper shows the preliminary clinical results of the trial on 5 chronic stroke patients throughout a 9 weeks, 3 hours per week, hand preshaping training.
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| 13. |
- De La Fuente, Alerie Guzman, et al.
(författare)
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Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:8, s. 1755-1764
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Tidskriftsartikel (refereegranskat)abstract
- The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfb(ret/ret) mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.
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| 14. |
- Friedman, Ran, et al.
(författare)
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Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology
- 2018
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Ingår i: Journal of Membrane Biology. - : Springer. - 0022-2631 .- 1432-1424. ; 251:5-6, s. 609-631
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Forskningsöversikt (refereegranskat)abstract
- This is a perspective article entitled "Frontiers in computational biophysics: understanding conformational dynamics of complex lipid mixtures relevant to biology" which is following a CECAM meeting with the same name.
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| 15. |
- Haas, Jan, et al.
(författare)
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Atlas of the clinical genetics of human dilated cardiomyopathy
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 36:18, s. 1123-U43
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.
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| 16. |
- He, Liqun, et al.
(författare)
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Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types
- 2018
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Ingår i: Scientific Data. - : NATURE PUBLISHING GROUP. - 2052-4463. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Vascular diseases are major causes of death, yet our understanding of the cellular constituents of blood vessels, including how differences in their gene expression profiles create diversity in vascular structure and function, is limited. In this paper, we describe a single-cell RNA sequencing (scRNA-seq) dataset that defines vascular and vessel-associated cell types and subtypes in mouse brain and lung. The dataset contains 3,436 single cell transcriptomes from mouse brain, which formed 15 distinct clusters corresponding to cell (sub) types, and another 1,504 single cell transcriptomes from mouse lung, which formed 17 cell clusters. In order to allow user-friendly access to our data, we constructed a searchable database (http://betsholtzlab.org/VascularSingleCells/database.html). Our dataset constitutes a comprehensive molecular atlas of vascular and vessel-associated cell types in the mouse brain and lung, and as such provides a strong foundation for future studies of vascular development and diseases.
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| 17. |
- Hvitfeldt-Forsberg, Helena, et al.
(författare)
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Staffs' and managers' perceptions of how and when discrete event simulation modelling can be used as a decision support in quality improvement : a focus group discussion study at two hospital settings in Sweden.
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore healthcare staffs' and managers' perceptions of how and when discrete event simulation modelling can be used as a decision support in improvement efforts.DESIGN: Two focus group discussions were performed.SETTING: Two settings were included: a rheumatology department and an orthopaedic section both situated in Sweden.PARTICIPANTS: Healthcare staff and managers (n=13) from the two settings.INTERVENTIONS: Two workshops were performed, one at each setting. Workshops were initiated by a short introduction to simulation modelling. Results from the respective simulation model were then presented and discussed in the following focus group discussion.RESULTS: Categories from the content analysis are presented according to the following research questions: how and when simulation modelling can assist healthcare improvement? Regarding how, the participants mentioned that simulation modelling could act as a tool for support and a way to visualise problems, potential solutions and their effects. Regarding when, simulation modelling could be used both locally and by management, as well as a pedagogical tool to develop and test innovative ideas and to involve everyone in the improvement work.CONCLUSIONS: Its potential as an information and communication tool and as an instrument for pedagogic work within healthcare improvement render a broader application and value of simulation modelling than previously reported.
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| 18. |
- Keller, Damián, et al.
(författare)
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Interaction Aesthetics and Ubiquitous Music
- 2015
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Ingår i: Creativity in the Digital Age. - London : Springer. - 9781447166801 ; , s. 91-105
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Two recent approaches to interaction design have good potential to address creative practice in everyday settings: interaction aesthetics and ubiquitous music. We discuss the theoretical and methodological issues raised by both perspectives and highlight the similarities and differences among the two approaches. Through the analysis of a series of experiments, a common theme emerges: relational properties may provide a useful target for creativity-oriented experimental work.
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| 19. |
- Keller, María Eugenia, et al.
(författare)
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Understanding the belief system of young people around alcohol consumption and road safety : the case of Argentina
- 2018
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Konferensbidrag (refereegranskat)abstract
- In Argentina, around five thousand people die each year due to road traffic crashes, turning road safety into a relevant subject for both state and society. In this context, since 2008 a leading governmental organization is dedicated to promote road safety among people in Argentina, the National Road Safety Agency (ANSV), whose goal is the decrease of morbid-mortality owed to this epidemic. In order to meet its objective, since 2011 the ANSV has carried out observational studies on drivers and passengers’ behavior all over the country, as well as socio-cultural studies to understand the perceptions and habits of the population in relation to road safety. Studies carried out in 2016 showed that young people are the most vulnerable group among all, in line with the literature available on the subject, due to their low use of safety elements and also because they are more likely to drive under the influence of alcohol, which is likely to lead to other risky behaviors. These results are not only supported by previous research showing that young drivers are the group most inclined to behave in a risky way in transit, but also by official statistics that show that traffic injuries constitute the first cause of death among young people between 15 and 34 years old. The present work has been designed parting from this general diagnosis, to understand the belief system and the social mechanisms that motivate the risky behavior of Argentinean youth among 16 and 30 years old in relation to alcohol intake associated to road safety. The general aim pursued with this research project is thus identifying the most relevant barriers to change that are impeding young road users to adopt a safe behavior. This study is the first stage of a larger project about the subject, finishing with the design and implementation of a policy intervention and the measurement of its estimated impact.In spite of the importance of the phenomenon of unsafe mobility patterns among the young due to alcohol consumption, little is known about how to address it. There is a widespread consensus in the Argentinean society that the issue is related with the lack of sufficient law enforcement, which is in fact partly related to the difficulties faced by a federal system of government when it comes to coordinating different bodies within different levels of government. Although still there are no clear solutions to the challenges that federalism imposes to road safety regarding alcohol consumption, local interventions could be implemented if there was a good diagnosis about this issue. However, there is little or no information: random alcohol controls are implemented all over the country by local police forces, but in most of the cases a proper statistical registry is not carried out. In this sense, there is an imperious need to generate evidence-based effective strategies to reduce risky behaviors.
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| 20. |
- Keller, Thomas, et al.
(författare)
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Historical increase in agricultural machinery weights enhanced soil stress levels and adversely affected soil functioning
- 2019
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Ingår i: Soil and Tillage Research. - : Elsevier BV. - 0167-1987 .- 1879-3444. ; 194
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Tidskriftsartikel (refereegranskat)abstract
- Soil compaction caused by vehicular traffic adversely affects key soil functions and ecosystem services that soils provide. Although compaction is a well-recognized problem, it remains challenging to quantify the economic and ecological costs of compaction. The mechanization in agriculture has resulted in a steady increase in weight of farm vehicles. It is reasonable to assume that this has exacerbated soil compaction, but there is little quantitative knowledge on the development of compaction levels in arable soils. To quantify these trends, we use historical records of harvester and tractor weights to simulate how the weight increase has changed soil stresses and bulk density of arable soil, and to predict impacts on the mechanical resistance for root growth and on soil hydraulic properties. Our simulations show a clear increase in soil stress levels with higher bulk density and mechanical penetration resistance, and a decrease in soil hydraulic conductivity in agreement with available data. We show that increased mechanical resistance has resulted in decreased root elongation rates and consequently prolonged the time required for roots to reach a certain soil depth. The historical changes of compaction levels and associated limitations on root elongation rates coincide with a stagnation in crop yields in the 1990s observed for cereals in many countries. Our calculations illustrate that the historical increase in compaction levels has drastically decreased saturated hydraulic conductivity and water storage capacity of subsoils. We speculate that this has contributed to the increase in the incidence and severity of flood events during recent decades in Europe. Finally, we take Sweden as an example and estimate annual compaction costs due to agricultural productivity loss and flooding damage of several hundred M(sic) yr(-1) for Sweden. Considering the continuation of upwards trends in the average weight of farm machinery and the projected increase in extreme weather events, the costs of soil compaction are likely to escalate. The study highlights that we have likely exceeded the acceptable loads, and that future agricultural operations must consider the inherent mechanical limit of soil.
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