| 1. |
- Liang, Liming, et al.
(författare)
-
An epigenome-wide association study of total serum immunoglobulin E concentration
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 520:7549, s. 670-U188
-
Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever' and allergic asthma'''. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation'. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations with a meta-analysis false discovery rate less than 10-4 between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies'''. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.
|
|
| 2. |
- Schriever, Valentin A., et al.
(författare)
-
Development of an International Odor Identification Test for Children : The Universal Sniff Test
- 2018
-
Ingår i: The Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 198, s. 265-272
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test.Study designThis is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). Results Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean +/- SD of 9.88 +/- 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r(27) = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%.ConclusionsThe U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.
|
|
| 3. |
- Bergström, Peter, 1975-
(författare)
-
Designing for the unknown : Didactical design for process-based assessment in technology-rich learning environments
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on a study of the development of education through theinnovative use of process-based assessment in technology-rich learningenvironments in teacher and nurse education. The study of process-basedassessment addresses the aim of creating a better understanding of the shiftin emphasis from teaching to learning with regard to theory and practice.The research questions address the use of process-based assessment, andhow the social relationships and issues of content can be understood intechnology-rich learning environments. A methodological approachinvolving design-based research was found to be especially applicable. Thestudy was designed in three iterative didactical design cycles for processbasedassessment in which the first and third cycles were analysed. Theempirical material comprises qualitative semi-structured interviews withteachers and students and questionnaires with students. The empiricalmaterial was analysed through inductive thematic analysis. The theoreticalanalyses in the comprising articles are mainly based on Bernstein’stheoretical framework for studying social relationships through concepts ofsymbolic power and control. For understanding change, with regard to theshift in emphasis from teaching to learning, the analysis is taken to a metalevelby applying Bernstein’s concept of pedagogical device.The results outline the shift in emphasis from teaching to learning fromboth a theoretical and practice perspective. Theoretically, the shift inemphasis from teaching to learning is based upon a shift in symbolic powerand control for teachers. In practice, the shift of symbolic power and controlbetween the teacher, student and content outline considerable overlapsbetween teacher-student, teacher-content and student-content. The overlapshighlight the empirical contribution in this thesis through the concept of“process” that is understood as a negotiation between teacher-student,teacher-content and student-content. The weakening symbolic powerrelationship made a multi-dimensional analysis of the teacher-studentcontentrelationship possible. Theoretically, the shift of symbolic poweroutlines a process of recontextualisation of a new discourse for teaching,learning and assessment. The multi-dimensional analysis highlights thetheoretical contributions to understanding the concept of discourse fromBernstein’s perspective through which the content and context create thediscourse. For practice, process-based assessment frames the notion ofdesigning for the unknown. Designing for the unknown is considered as aframework based upon a set of rules through which teachers and studentsadapt to a problematising approach in teaching, learning and assessment
|
|
| 4. |
- Fagerberg, Linn, et al.
(författare)
-
Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
-
Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
-
Tidskriftsartikel (refereegranskat)abstract
- A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
|
|
| 5. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
-
Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
|
|
| 6. |
- Granberg, Carina, 1966-
(författare)
-
ICT and learning in teacher education : The social construction of pedagogical ICT discourse and design
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background In recent decades, system-wide policies and substantial resources have been directed towards enhancing the use of ICT in learning contexts. This development can be observed at international and national levels. However, reports have indicated a ’slow uptake’ of the use of ICT for pedagogical purposes among compulsory schools and teacher education institutions. Although the teacher education at Umeå University follows this pattern, there have been several initiatives in using ICT for learning in the teacher education programmes. The aim of this study is to scrutinise the process in which ICT-supported methods for learning have been introduced, used and disseminated throughout teacher education. Methods Three ICT-supported methods for teaching and learning were chosen for this study: digital individual development planning (IUP), blogs and e-portfolios. To capture teachers’ and students’ experiences of introducing the pedagogical use of ICT, 115 interviews were conducted and four questionnaires were administered over a four-year period (2006-2010). Course documents and observations of blogs and e-portfolios supplied additional data. Hermeneutics was chosen as the methodological approach. Thematic content analysis was carried out in the first three part-studies, and theoretical frameworks suited for the identified themes were chosen for the analyses. Since pedagogical discourses appeared to be important, discourse analysis was used in the fourth part-study. A final meta analysis has been carried out and is presented later in this thesis. Results In Umeå, as in other countries, teacher education has been slow to adopt ICT for learning. Still, the use of ICT for learning has increased over time. ICT-supported methods such as IUP, blogs and e-portfolios have found their way into the context through a recontextualisation process in which ICT discourses and designs are socially constructed. However, the recontextualisation process could merely be found within sub-fields, such as teacher teams and project groups, since in the main-field (i.e. teacher education) traditional ways of teaching and learning have been internalised. These traditions hold symbolic capital, and teachers who have the means to do so will act according to their habitus and defend the traditions. The recontextualisation process will therefore be kept within the sub-fields, and the dissemination will be limited. Furthermore, the sub-fields are rather isolated from one another, and therefore pedagogical ICT discourses and designs are created in varied ways. However, none of them could be regarded as internalised, and the social construction of pedagogical ICT discourse and design has to be considered to be still ‘under construction’.
|
|
| 7. |
- Herrick, Ariane L, et al.
(författare)
-
Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
|
|
| 8. |
- Horvath, Rita, et al.
(författare)
-
Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.
- 2009
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 132:Pt 11, s. 3165-74
-
Tidskriftsartikel (refereegranskat)abstract
- Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.
|
|
| 9. |
- Huyghe, Jeroen R, et al.
(författare)
-
Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
-
Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
|
|
| 10. |
- Lehikoinen, Aleksi, et al.
(författare)
-
Wintering bird communities are tracking climate change faster than breeding communities
- 2021
-
Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 90:5, s. 1085-1095
-
Tidskriftsartikel (refereegranskat)abstract
- Global climate change is driving species' distributions towards the poles and mountain tops during both non-breeding and breeding seasons, leading to changes in the composition of natural communities. However, the degree of season differences in climate-driven community shifts has not been thoroughly investigated at large spatial scales. We compared the rates of change in the community composition during both winter (non-breeding season) and summer (breeding) and their relation to temperature changes. Based on continental-scale data from Europe and North America, we examined changes in bird community composition using the community temperature index (CTI) approach and compared the changes with observed regional temperature changes during 1980–2016. CTI increased faster in winter than in summer. This seasonal discrepancy is probably because individuals are less site-faithful in winter, and can more readily shift their wintering sites in response to weather in comparison to the breeding season. Regional long-term changes in community composition were positively associated with regional temperature changes during both seasons, but the pattern was only significant during summer due to high annual variability in winter communities. Annual changes in community composition were positively associated with the annual temperature changes during both seasons. Our results were broadly consistent across continents, suggesting some climate-driven restructuring in both European and North American avian communities. Because community composition has changed much faster during the winter than during the breeding season, it is important to increase our knowledge about climate-driven impacts during the less-studied non-breeding season.
|
|
