| 1. |
- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 2. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Abazajian, Kevork, et al.
(author)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Journal article (peer-reviewed)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 4. |
- Addo, Rebecka N., et al.
(author)
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Olfactory Functions in Adults With Autism Spectrum Disorders
- 2017
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In: Perception. - : SAGE Publications. - 0301-0066 .- 1468-4233. ; 46:3-4, s. 530-537
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.
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| 5. |
- Bergman, Anna Carin, et al.
(author)
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dUTPase from the Retrovirus Equine Infectious Anemia Virus: High-Level Expression in Escherichia coli and Purification
- 1995
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In: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 6:3, s. 379-387
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Journal article (peer-reviewed)abstract
- Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase, EC 3.6.1.23) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate, and plays important roles in nucleotide metabolism and DNA replication. The dUTPase gene of the retrovirus equine infectious anemia virus (EIAV) was cloned and overexpressed in Escherichia coli using the T7 RNA polymerase expression system. The recombinant vector (pET-3a/EDU), constructed by mutagenic PCR, was transformed into E. coli BL21(DE3) pLysS cells, resulting in expression of EIAV dUTPase at about 40% of the extracted protein, This level of overproduction is very high compared to previous reports on heterologous expression of dUTPases in E. coli. A one-step purification procedure using phosphocellulose chromatography results in a homogeneous preparation of the enzyme in a yield of 45 mg liter−1 of bacterial culture. The purified EIAV dUTPase, run on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis, shows an apparent molecular mass of 15.1 kDa in accordance with the gene structure. The isoelectric point (pI) was determined to 5.6. Gel filtration under nondenaturating conditions gives a retention volume corresponding to a molecular mass of 40.8 kDa, suggesting a trimeric organization of the enzyme. The amino acid composition and amino-terminal sequence of the recombinant dUTPase are in agreement with predictions from the DNA sequence.
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| 6. |
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| 7. |
- Brazier, J, et al.
(author)
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European surveillance study on antimicrobial susceptibility of Gram-positive anaerobic cocci
- 2008
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In: International Journal of Antimicrobial Agents. - Amsterdam : Elsevier. - 0924-8579 .- 1872-7913. ; 31:4, s. 316-320
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Journal article (peer-reviewed)abstract
- Gram-positive anaerobic cocci (GPAC) are a heterogeneous group of microorganisms frequently isolated from local and systemic infections. In this study, the antimicrobial susceptibilities of clinical strains isolated in 10 European countries were investigated. After identification of 299 GPAC to species level, the minimum inhibitory concentrations of penicillin, imipenem, clindamycin, metronidazole, vancomycin and linezolid were determined by the agar dilution method according to the Clinical and Laboratory Standards Institute. The majority of isolates were identified as Finegoldia magna and Parvimonas micra (formerly Peptostreptococcus micros), isolated from skin and soft tissue infections. All isolates were susceptible to imipenem, metronidazole, vancomycin and linezolid. Twenty-one isolates (7%) were resistant to penicillin (n=13) and/or to clindamycin (n=12). Four isolates were resistant to both agents. The majority of resistant isolates were identified as F. magna and originated from blood, abscesses and soft tissue infections.
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| 8. |
- Cheddad, Abbas, et al.
(author)
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Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion
- 2013
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In: Optics Express. - : Optical Society of America. - 1094-4087. ; 21:14, s. 16584-16604
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Journal article (peer-reviewed)abstract
- We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods.
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| 9. |
- Davidsson, Josef, et al.
(author)
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Array-based genotype-phenotype correlation in a case of supernumerary ring chromosome 12
- 2008
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In: Clinical Genetics. - : Wiley. - 0009-9163. ; 73:1, s. 44-49
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Journal article (peer-reviewed)abstract
- Supernumerary ring chromosomes (SRC) account for approximately 10% of prenatal marker chromosomes and 60% of these SRCs are associated with an abnormal phenotype of the patient carrying them. SRCs have, with few exceptions, not been characterized at the molecular genetic level. Here, we present the first case of a SRC 12 thoroughly investigated with tiling resolution array-based comparative genomic hybridization (array CGH); multicolor, centromere, subtelomeric and whole chromosome painting fluorescence in situ hybridization. In addition, to be able to correlate phenotypic manifestations with a possible pathogenetic outcome of the SRC 12, we retrospectively compared and reviewed all 14 cases of SRC 12 reported, including our present case. Our analyses revealed that the SRC comprised 25.53-46.40 Mb of chromosome 12, a region known to harbor 47 annotated genes of which nine were of putative pathogenetic relevance. Reviewing the previously described cases of SRC 12, we could not establish any specific recurrent features associated with this type of SRC. This most probably reflects heterogeneity in break-point distribution among the reported cases, resulting in differently sized ring chromosomes and hence varying phenotypic traits of the patients. Detailed genomic evaluation, by array CGH or similar techniques may thus be of importance to predict the clinical course in individual cases.
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| 10. |
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| 11. |
- Dennhag, Nils, 1989-, et al.
(author)
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fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- In muscular dystrophies, muscle fibers loose integrity and die, causing significant suffering and premature death. Strikingly, the extraocular muscles (EOMs) are spared, functioning well despite the disease progression. Although EOMs have been shown to differ from body musculature, the mechanisms underlying this inherent resistance to muscle dystrophies remain unknown. Here, we demonstrate important differences in gene expression as a response to muscle dystrophies between the EOMs and trunk muscles in zebrafish via transcriptomic profiling. We show that the LIM-protein Fhl2 is increased in response to the knockout of desmin, plectin and obscurin, cytoskeletal proteins whose knockout causes different muscle dystrophies, and contributes to disease protection of the EOMs. Moreover, we show that ectopic expression of fhl2b can partially rescue the muscle phenotype in the zebrafish Duchenne muscular dystrophy model sapje, significantly improving their survival. Therefore, Fhl2 is a protective agent and a candidate target gene for therapy of muscular dystrophies.
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| 12. |
- Edsjö, Anders, et al.
(author)
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Building a precision medicine infrastructure at a national level : The Swedish experience
- 2023
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In: Cambridge Prisms: Precision Medicine. - : Cambridge University Press. - 2752-6143. ; 1
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Research review (peer-reviewed)abstract
- Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.
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| 13. |
- Ekdahl, Anna-Lena, et al.
(author)
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Different opportunities to learn subtraction bridging through ten in grade 1
- 2021
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In: EARLI2021 Book of abstracts. ; , s. 36-36
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Conference paper (peer-reviewed)abstract
- Teaching addition and subtraction using 10 as a benchmark is seen as a powerful strategy for advancing pupils’ learning of arithmetic skills when solving tasks like 13-5. Using 10 as a benchmark for solving the task entails for example that the pupils need to be aware of that 5 can be partitioned into 3 and 2, and that the task may be solved in two steps, 13-3=10, and 10-2=8. In this study two lessons in two grade 1 classes, taught by different teachers, are analyzed on a finegrained level. Our aim is to exemplify and discuss how 10 as a benchmark is used in teaching subtraction bridging through ten and what that may imply for pupils’ learning. Our research question is; What different opportunities to learn ‘10 as a benchmark’ are offered in two lessons of subtraction in the number range of 1 to 20? Variation theory (Marton, 2015) is the theoretical framework used for analysis. The analysis shows how different opportunities to learn subtraction bridging through ten are offered in the lessons by the aspects of the content brought to the fore for the pupils to experience.
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| 14. |
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| 15. |
- Eklund Heinonen, Maria, 1966-, et al.
(author)
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”Mer än bara text och ord”: Akademiskt skrivande i utbildningar i socialt arbete och sociologi
- 2018
-
Reports (other academic/artistic)abstract
- This report was initiated by the Department of Sociology at Uppsala University and aims to investigate how the department helps its students to develop academic literacies. Another aim is to provide suggestions on how the department can develop teaching practices in order to integrate writing within its courses. In the report, we have examined course designs, learning outcomes and writing instructions. In addition, we have interviewed teachers and analyzed students’ texts. The report is concluded by some general suggestions on how the department can continue to support the students’ academic literacies.
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| 16. |
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| 17. |
- Fredriksson, Maria, et al.
(author)
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Water sorption in wood cell walls–data exploration of the influential physicochemical characteristics
- 2023
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In: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 30:3, s. 1857-1871
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Journal article (peer-reviewed)abstract
- The material properties of wood are intimately tied to the amount of moisture contained in the wood cell walls. The moisture content depends on the environmental conditions, i.e. temperature and relative humidity, but also on material characteristics of the wood itself. The exact mechanisms governing moisture equilibrium between wood cell walls and environmental conditions remain obscure, likely because multiple material characteristics have been proposed to be involved. In this study, we used a data exploration approach to illuminate the important wood characteristics determining the cell wall moisture content in the full moisture range. Specimens of nine different wood species (two softwoods and seven hardwoods) were examined in terms of their material characteristics at multiple scales and their cell wall moisture content was measured in equilibrium with both hygroscopic conditions and at water-saturation. By statistical analysis, the chemical composition was found to be the most important predictor of the cell wall moisture content in the full moisture range. For the other wood characteristics the importance differed between the low moisture range and the humid and saturated conditions. In the low moisture range, the cellulose crystallinity and hydroxyl accessibility were found to be important predictors, while at high moisture contents the microfibril orientation in the S1 and S3 layers of the cell walls was important. Overall, the results highlighted that no single wood characteristic were decisive for the cell wall moisture content, and each of the predictors identified by the analysis had only a small effect in themselves on the cell wall moisture content. Wood characteristics with a major effect on the cell wall moisture content were, therefore, not identified.
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| 18. |
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| 19. |
- Gaber, Flora, et al.
(author)
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Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma
- 2008
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In: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 63:12, s. 1076-82
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Journal article (peer-reviewed)abstract
- BACKGROUND: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E(4) (LTE(4)) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B(4) (LTB(4)) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators. METHODS: Induced sputum, saliva, urine and blood were obtained at baseline from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB(4) and the prostaglandin D(2) metabolite 9alpha,11beta-prostaglandin F(2) were performed and the fraction of exhaled nitric oxide was measured. RESULTS: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB(4) levels between the groups. Levels of urinary LTE(4) and 9alpha,11beta-prostaglandin F(2) increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase. CONCLUSION: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.
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| 20. |
- Gebre-Medhin, Samuel, et al.
(author)
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Recurrent Rearrangement of the PHF1 Gene in Ossifying Fibromyxoid Tumors.
- 2012
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In: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 181:3, s. 1069-1077
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Journal article (peer-reviewed)abstract
- Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor of unknown lineage. Although most cases are histologically and clinically benign, some show malignant morphological features and local recurrences are not uncommon; a few may even metastasize. In the present study, cytogenetic analysis identified different structural rearrangements of chromosome band 6p21 in tumor cells from three cases of OFMT, including one with typical, one with atypical, and one with malignant morphological features. Mapping of the 6p21 breakpoint by fluorescence in situ hybridization (FISH) indicated that the PHF1 gene was rearranged in all three cases. Further FISH, 5'-rapid amplification of cDNA ends, and RT-PCR analyses disclosed an EP400/PHF1 fusion transcript in one of the cases. Interphase FISH on tumor sections from 13 additional cases of OFMT showed rearrangement of the PHF1 locus in four of four typical, two of three atypical, and one of six malignant lesions. Thus, the PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of OFMTs, irrespective of whether they are diagnosed as typical, atypical, or malignant lesions. The PHF1 protein interacts with the polycomb-repressive complex 2 (PRC2), which, in turn, regulates the expression of a variety of developmental genes. Thus, the results indicate that deregulation of PRC2 target genes is crucial for OFMT development.
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| 21. |
- Grong, Eivind, et al.
(author)
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Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography
- 2016
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In: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 30:2, s. 532-542
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Journal article (peer-reviewed)abstract
- Background In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.Methods Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.Results Body weight did not differ between groups (Pg = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (Pg = 0.037); HbA1c levels in SG were lower compared to DJ only (p\0.05). GLP-1 levels were elevated for DJ compared to SG and sham (Pg = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (Pg = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).Conclusion Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.
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| 22. |
- Hahn, Max, et al.
(author)
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3D imaging of human organs with micrometer resolution - applied to the endocrine pancreas
- 2021
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Journal article (peer-reviewed)abstract
- The possibility to quantitatively study specific molecular/cellular features of complete human organs with preserved spatial 3D context would have widespread implications for pre-clinical and clinical medicine. Whereas optical 3D imaging approaches have experienced a formidable revolution, they have remained limited due to current incapacities in obtaining specific labelling within large tissue volumes. We present a simple approach enabling reconstruction of antibody labeled cells within entire human organs with preserved organ context. We demonstrate the utility of the approach by providing volumetric data and 3D distribution of hundreds of thousands of islets of Langerhans within the human pancreas. By assessments of pancreata from non-diabetic and type 2 diabetic individuals, we display previously unrecognized features of the human islet mass distribution and pathology. As such, this method may contribute not only in unraveling new information of the pancreatic anatomy/pathophysiology, but it may be translated to essentially any antibody marker or organ system.
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| 23. |
- Hahn, Max, et al.
(author)
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Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence
- 2020
-
In: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
-
Journal article (peer-reviewed)abstract
- The possibility to assess pancreatic anatomy with microscopic resolution in three dimensions (3D) would significantly add to pathological analyses of disease processes. Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis with over 90% of the patients dying within 5 years after diagnosis. Cure can be achieved by surgical resection, but the efficiency remains drearily low. Here we demonstrate a method that without prior immunohistochemical labelling provides insight into the 3D microenvironment and spread of PDAC and premalignant cysts in intact surgical biopsies. The method is based solely on the autofluorescent properties of the investigated tissues using optical projection tomography and/or light-sheet fluorescence microscopy. It does not interfere with subsequent histopathological analysis and may facilitate identification of tumor-free resection margins within hours. We further demonstrate how the developed approach can be used to assess individual volumes and numbers of the islets of Langerhans in unprecedently large biopsies of human pancreatic tissue, thus providing a new means by which remaining islet mass may be assessed in settings of diabetes. Generally, the method may provide a fast approach to provide new anatomical insight into pancreatic pathophysiology.
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| 24. |
- Hahn, Max, et al.
(author)
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Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes
- 2020
-
In: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Mouse models of Streptozotocin (STZ) induced diabetes represent the most widely used preclinical diabetes research systems. We applied state of the art optical imaging schemes, spanning from single islet resolution to the whole organ, providing a first longitudinal, 3D-spatial and quantitative account of β-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced β-cell destruction predominantly affects large islets in the pancreatic core. Further, we show that hyperglycemic STZ-treated mice still harbor a large pool of remaining β-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired β-cell maturity. Reversing hyperglycemia by islet transplantation partially restored the expression of markers for islet function, but not BCM. Jointly our results indicate that STZ-induced hyperglycemia results from β-cell dysfunction rather than β-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.
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| 25. |
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| 26. |
- Hallesson, Yvonne, FD, Docent, et al.
(author)
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Rörelser mellan konkretion och abstraktion i diskursivt skrivande : Semantiska vågor i elevtexter från två nationella provuppgifter i svenska
- 2022
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In: Fjortonde nationella konferensen i svenska med didaktisk inriktning. - Lund : Media-Tryck. - 9789178772841 - 9789178772858 ; , s. 95-114
-
Conference paper (peer-reviewed)abstract
- I studien analyseras elevtexter från två olika diskursiva skrivuppgifter från detnationella provet i Svenska 1 i relation till uppgiftsformuleringar ochtextunderlag. Det övergripande syftet är att undersöka vad som utmärkerelevtexterna semantiskt och om innehållsliga mönster framträder som kanrelateras till uppgiftsformulering respektive till olika betyg, för att mer specifiktutforska vad som utmärker elevtexterna utifrån hur de växlar mellan partier medmer abstrakt och mer konkret/personligt innehåll och mellan olika perspektiv.Materialet består av 40 elevtexter representerande betygsstegen B, C, D och E.Analysverktyget är hämtat från Legitimation Code Theory, LCT (Maton 2013,2014, 2019) där semantisk tyngd undersöks genom analys av semantiskavågorrörelser inom elevtexterna. För att fördjupa analyserna har också en enkelform av pronomenanalys genomförts. Resultatet visar att de olikaskrivuppgifterna leder till texter med olika grad av variation i vågrörelserna. Förden ena uppgiften synliggörs en viss tendens till att texter med högre betyg visarstörre vågrörelser mellan abstrakta och konkreta innehållsliga delar, medan textermed lägre betyg inte visar lika tydlig variation. För den andra uppgiftensynliggörs inga tydliga skillnader mellan texter med olika betyg, utan där ärvågrörelserna överlag mer begränsade, utom för texterna på D-nivå. En slutsatskan vara att uppgifternas utformning öppnar upp för två olika typer avställningstaganden, där den ena ger utrymme att skriva en innehållsligt merkomplex text, vilket i sig ger bättre underlag för att differentiera mellan de olikabetygsstegen. Uppgiftens formulering tillsammans med dess källmaterial tyckssåledes påverka vilken typ av skrivande som möjliggörs.
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| 27. |
- Hallesson, Yvonne, et al.
(author)
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Semantiska vågor i diskursiva elevtexter : En analysmodell
- 2022
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In: Språk i skola, på fritid och i arbetsliv. - : ASLA, Svenska föreningen för tillämpad språkvetenskap. - 9789187884290 ; , s. 31-54
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Book chapter (peer-reviewed)abstract
- Under skoltiden förväntas elever utveckla förmåga att skriva diskursiva texter, dvs. utredande argumenterade och resonerande texter. Medan många modeller för diskursivt skrivande tar fasta på strukturella eller lexikogrammatiska aspekter är det emellertid desto svårare att fånga hur innehållsliga aspekter integreras, exempelvis rörelser mellan olika abstraktionsnivåer. I den här artikeln illustreras hur verktyg från Legitimation Code Theory (Maton, 2013, 2014, 2019) kan tillämpas för att analysera hur olika former av kunskap samverkar i diskursiva texter, exempelvis för att anlägga ett samhällsperspektiv på mer lokala företeelser. Den dimension som har använts är Semantic gravity – semantisk tyngd (Maton, 2014) – som synliggör i vad mån mer kontextbunden kunskap, såsom observationer eller erfarenheter, länkas ihop med mer generaliserad och/eller teoretisk kunskap. Artikelns syfte är att visa hur analys av semantisk tyngd kan identifiera och beskriva innehållsaspekter av diskursiva elevtexter som annars inte är så lätta att beskriva. I artikeln exemplifieras hur en analys rent konkret kan genomföras för ett material bestående av diskursiva elevtexter producerade inom det nationella provet i svenska på gymnasiet. Avväganden och utmaningar i genomförandet beskrivs och för- och nackdelar med modellen diskuteras. En slutsats är att modellen potentiellt kan bidra både som analysredskap och som didaktiskt redskap i skrivundervisning.
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| 28. |
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| 29. |
- Hamdi, Yosr, et al.
(author)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
-
Journal article (peer-reviewed)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 30. |
- Hedberg, Maria, et al.
(author)
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Anaerobic bacteria
- 2008. - 3rd
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In: Antimicrobial therapy and vaccines. - New York : Apple Trees Production, LLC.
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Book chapter (other academic/artistic)
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| 31. |
- Hedhammar, My, et al.
(author)
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A Novel flow cytometry-based method for analysis of expression levels in Escherichia coli, giving information about precipitated and soluble protein
- 2005
-
In: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 119:2, s. 133-146
-
Journal article (peer-reviewed)abstract
- A high throughput method for screening of protein expression is described. By using a flow cytometer, levels of both soluble and precipitated protein can simultaneously be assessed in vivo. Protein fragments were fused to the N-terminus of enhanced GFP and the cell samples were analysed using a flow cytometer. Data concerning whole cell fluorescence and light scattering was collected. The whole cell fluorescence is probing intracellular concentrations of soluble fusion proteins. Concurrently, forward scattered light gives data about inclusion body formation, valuable information in process optimisation. To evaluate the method, the cells were disrupted, separated into soluble and non-soluble fractions and analysed by gel electrophoresis. A clear correlation between fluorescence and soluble target protein was shown. Interestingly, the distribution of the cells regarding forward scatter (standard deviation) correlates with the amount of inclusion bodies formed. Finally, the newly developed method was used to evaluate two different purification tags, His(6) and Z(basic), and their effect on the expression pattern.
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| 32. |
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| 33. |
- Högström, Ebba, 1961-
(author)
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Kalejdoskopiska rum : Diskurs, materialitet och praktik i den decentraliserade psykiatriska vården
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- During the period 1967-1995, Swedish mental healthcare underwent a complete re-organisation, starting with county councils taking over responsibility for mental healthcare from the state. Asylums were then phased out and mental health care moved closer to patients. The Mental Health Reform of 1995 completed this decentralisation and put the emphasis on an independent and integrated life as a citizen in society and the idea of a dwelling of one’s own. This thesis describes and analyses spatial aspects of decentralised mental healthcare in Sweden, focusing on the decentralisation discourse regarding organisation, localisation, patient care and working methods behind decentralisation and its spatial performance. A case study of decentralised mental healthcare in Nacka, a Stockholm suburb, between 1958-1999 examines in particular the emerging decentralisation discourse 1958-1973, The Nacka Project 1974-1980 (one of the first examples of community care in Sweden), psychiatry in Nacka 1980-1994 and the official report Welfare and Freedom of Choice from 1995. The methods used include studies of documents, interviews, visual and architectural drawing analysis. The theoretical point of departure for the analysis is a post-structural heterogeneous concept of space where spatial materiality and discursiveness are looked upon as intertwined. The result shows that the re-organisation of mental healthcare brought about a substantial spatial transformation. Normalisation of patients’ lives involved integration into society and support for independent living. The local environment was the main trope for the early stage of decentralised mental healthcare, but the notion of a dwelling of one’s own became the important trajectory to an independent life after 1995. The idea of the patient is challenged by the independence discourse, which could be said to contain an idea of the ‘non-patient’. Overall, it can be concluded that spatial organisations of the built environment are never value-free or neutral. They reflect, enable and constrain power relations in a society and material space can contribute to the power of one group at the expense of another. Furthermore, the results of the spatialities, or the meanings, cannot be predicted. It is therefore crucial to distinguish power in all its configurations and scales and to keep negotiations alive, especially within the field of mental healthcare, but also in the care sector as a whole and in other societal institutions where policies buildings and built environment interact with user practices. This kaleidoscopic perspective can be used for examining complexities in the past and present and for encouraging future potentialities in the process of making/enacting spatial relations.
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| 34. |
- Isaksson, Caroline, et al.
(author)
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Species-Dependent Effects of the Urban Environment on Fatty Acid Composition and Oxidative Stress in Birds
- 2017
-
In: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 5
-
Journal article (peer-reviewed)abstract
- Ecological impacts of urbanization include the loss of biodiversity and changes in species composition and population densities. However, how the urban environment affects fundamental physiological parameters is largely unknown. Here, we investigated physiological components related to health and nutrition, namely, plasma fatty acids (FA) and lipid peroxidation at inter-habitat and interspecific levels. Specifically, we compared four passerine bird species—the great tit (Parus major), the blue tit (Cyanistes caeruleus), the house sparrow (Passer domesticus), and the tree sparrow (P. montanus)—from urban and rural environments. Significant interactions between species and habitat were revealed for the majority of the FAs. Interestingly, the observed inter-habitat variation in FAs was frequently in opposite directions when comparing species from the two families (tits, Paridae; sparrows, Passeridae). These patterns suggest that sparrows and tits feed on different food sources, or modulate their FA metabolism differently, across the urban-rural gradient. By using canonical discriminant analyses (CDA), we further demonstrated species-specific signals in FA composition, with misclassification of species being <1% within habitats and <7% between habitats. Finally, the urban-rural FA differences between species and families were manifested in two indices of health. Firstly, urban blue tits had a higher total ω-6/ω-3 polyunsaturated FA ratio than rural conspecifics, which is believed to increase inflammatory responses. Secondly, urban sparrows of both species showed higher lipid peroxidation indices (indicating a higher susceptibility to lipid peroxidation if exposed to pro-oxidants), and consequently, a higher level of lipid peroxidation compared to their rural conspecifics. Collectively, the species- and habitat-specific differences in plasma FA composition, which are linked to nutrition and metabolism, suggest that the urban environment affect tits and sparrows primarily via two different pathways—inflammation and oxidative stress, respectively,—with potential consequences for the health of urban populations.
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| 35. |
- Jin, Yuesheng, et al.
(author)
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Distinct mitotic segregation errors mediate chromosomal instability in aggressive urothelial cancers.
- 2007
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In: Clinical Cancer Research. - 1078-0432. ; 13:6, s. 1703-1712
-
Journal article (peer-reviewed)abstract
- Purpose: Chromosomal instability (CIN) is believed to have an important role in the pathogenesis of urothelial cancer (UC). The aim of this study was to evaluate whether disturbances of mitotic segregation contribute to CIN in UC, if these processes have any effect on the course of disease, and how deregulation of these mechanisms affects tumor cell growth. Experimental Design: We developed molecular cytogenetic methods to classify mitotic segregation abnormalities in a panel of UC cell lines. Mitotic instabilities were then scored in biopsies from 52 UC patients and compared with the outcome of tumor disease. Finally, UC cells were exposed in vitro to a telomerase inhibitor to assess how this affects mitotic stability and cell proliferation. Results: Three distinct chromosome segregation abnormalities were identified: (a) telomere dysfunction, which triggers structural rearrangements and loss of chromosomes through anaphase bridging; (b) sister chromatid nondisjunction, which generates discrete chromosomal copy number variations; and (c) supernumerary centrosomes, which cause dramatic shifts in chromosome copy number through multipolar cell division. Chromosome segregation errors were already present in preinvasive tumors and a high rate mitotic instability was an independent predictor of poor survival. However, induction of even higher levels of the same segregation abnormalities in UC cells by telomerase inhibition in vitro led to reduced tumor cell proliferation and clonogenic survival. Conclusion: Several distinct chromosome segregation errors contribute to CIN in UC, and the rate of such mitotic errors has a significant effect on the clinical course. Efficient tumor cell proliferation may depend on the tight endogenous control of these processes.
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| 36. |
- Jin, Yuesheng, et al.
(author)
-
Fusion of the AHRR and NCOA2 genes through a recurrent translocation t(5;8)(p15;q13) in soft tissue angiofibroma results in upregulation of aryl hydrocarbon receptor target genes.
- 2012
-
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 51:5, s. 510-520
-
Journal article (peer-reviewed)abstract
- Soft tissue angiofibroma is a recently delineated tumor type of unknown cellular origin. Cytogenetic analysis of four cases showed that they shared a t(5;8)(p15;q13). In three of them it was the sole change, underlining its pathogenetic significance. FISH mapping suggested the involvement of the aryl hydrocarbon receptor repressor (AHRR) and nuclear receptor coactivator 2 (NCOA2) genes in 5p15 and 8q13, respectively. RT-PCR revealed in-frame AHRR/NCOA2 and NCOA2/AHHR transcripts in all four cases. Interphase FISH on paraffin-embedded tissue from 10 further cases without cytogenetic data showed that three were positive for fusion of AHRR and NCOA2. While AHRR has never been implicated in gene fusions before, NCOA2 is the 3'-partner in fusions with MYST3 and ETV6 in leukemias and with PAX3 and HEY1 in sarcomas. As in the previously described fusion proteins, NCOA2 contributes with its two activation domains to the AHRR/NCOA2 chimera, substituting for the repressor domain of AHRR. Because the amino terminal part of the transcription factor AHRR, responsible for the recognition of xenobiotic response elements in target genes and for heterodimerization, shows extensive homology with the aryl hydrocarbon receptor (AHR), the fusion is predicted to upregulate the AHR/ARNT signaling pathway. Indeed, global gene expression analysis showed upregulation of CYP1A1 as well as other typical target genes of this pathway, such as those encoding toll-like receptors. Apart from providing a diagnostic marker for soft tissue angiofibroma, the results also suggest that this tumor constitutes an interesting model for evaluating the cellular effects of AHR signaling. © 2012 Wiley Periodicals, Inc.
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| 37. |
- Koblmüller, Stephan, et al.
(author)
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More is Better
- 2009
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In: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 18:24, s. 4994-4996
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Journal article (other academic/artistic)
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| 38. |
- Koblmuller, Stephan, et al.
(author)
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Origin and status of the Great Lakes wolf
- 2009
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In: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 18:11, s. 2313-2326
-
Journal article (peer-reviewed)abstract
- An extensive debate concerning the origin and taxonomic status of wolf-like canids in the North American Great Lakes region and the consequences for conservation politics regarding these enigmatic predators is ongoing. Using maternally, paternally and biparentally inherited molecular markers, we demonstrate that the Great Lakes wolves are a unique population or ecotype of gray wolves. Furthermore, we show that the Great Lakes wolves experienced high degrees of ancient and recent introgression of coyote and western gray wolf mtDNA and Y-chromosome haplotypes, and that the recent demographic bottleneck caused by persecution and habitat depletion in the early 1900s is not reflected in the genetic data.
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| 39. |
- Kullberg, Angelika, et al.
(author)
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Afforded and experienced variation
- 2021
-
In: The Earli Sig 9 Conference, 10-11 February 2021. ; , s. 20-20
-
Conference paper (peer-reviewed)abstract
- The use of variation theory as a tool for designing lessons has been widely applied and received a lot of attention e.g. in mathematics education. More limited attention has been given to the use of variation theory as a means to analyze teaching and learning. This theoretical paper addresses the connection between the afforded and experienced variation when analyzing teaching and learning with a variation theory framework. Variation theory is in this case used as a tool for analyzing the relationship between teaching and learning, exploring the enacted, and lived object of learning. The connection between what is afforded in teaching and what students learn, can in this way be described in commensurable terms. With examples from a study about students’ learning of number relations in mathematics in first grade, we highlight this connection by illustrating differences identified in the teachers enactment of the same task, and what the students’ learned.
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| 40. |
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| 41. |
- Kullberg, Angelika, 1969, et al.
(author)
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Teaching and learning addition and subtraction bridging through ten using a structural approach
- 2022
-
In: Fernández, C., Llinares, S., Gutiérrez, A., & Planas, N. (Eds.) Proceedings of the 45th Conference of the International Group for the Psychology of Mathematics Education (Vol. 3, pp. 83-90). Alicante, Spain: PME. - Alicante, Spain : PME. - 9788413021768
-
Conference paper (peer-reviewed)abstract
- An eight-month-long intervention based on the idea of using a structural approach to addition and subtraction, and particularly bridging through ten, was implemented in Swedish Grade 1. A goal was that at the end of Grade 1, students would solve tasks like 15–7= using part-whole relations of numbers. In this paper, we report on learning outcomes from task-based interviews with intervention and control groups before, immediately after and one year after the intervention, to investigate long-term effects and whether students used a structural approach when solving tasks in Grade 2. Results show that students in the intervention group increased their learning outcomes the most and to a larger extent solved tasks in higher number ranges using a structural approach.
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| 42. |
- López, María-Eugenia, et al.
(author)
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Lack of panmixia of Bothnian Bay vendace-Implications for fisheries management
- 2022
-
In: Frontiers in marine science. - : Frontiers Media SA. - 2296-7745. ; 9
-
Journal article (peer-reviewed)abstract
- Overexploitation of fisheries is recognized as a major environmental and socioeconomic problem that threats biodiversity and ecosystem functioning. Inappropriate management policies of fish stocks have been applied as a consequence of inadequate characterization of subtle genetic structure in many fish species. In this study, we aim to assess the extent of genetic differentiation and structure of vendace (Coregonus albula) collected from eight locations in the Bothnian Bay, the northernmost part of the Baltic Sea. Specifically, we test if this species forms a single panmictic population or is divided into several genetically distinct units. We used restriction site-associated DNA sequencing (RAD-seq) to identify 21,792 SNPs based on 266 individuals. We identified a clear pattern of genetic differentiation between River Kalix and the other sampling locations, and a weak structuring between samples from Swedish and Finnish coast. Outlier analysis detected 41 SNPs putatively under divergent selection, mainly reflecting the divergence between River Kalix and the other samples. The outlier SNPs were located within or near 25 genes, including voltage-dependent calcium channel subunit alpha-2 (CACNA2D2), cadherin 26 (CDH26) and carbonic anhydrase 4-like (CA4) that have earlier been associated with salt-tolerance and salinity stress. Our study provides the first genome-wide perspective on genetic structuring of Baltic Sea vendace and rejects the hypothesis of panmixia in the Bothnian Bay. As such, our work demonstrates the power of RAD-sequencing to detect low but significant genetic structuring relevant for fisheries management.
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| 43. |
- Macchia, Gemma, et al.
(author)
-
FOSL1 as a candidate target gene for 11q12 rearrangements in desmoplastic fibroblastoma.
- 2012
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In: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 92:5, s. 735-743
-
Journal article (peer-reviewed)abstract
- Desmoplastic fibroblastoma (DF) is a benign fibroblastic/myofibroblastic tumor. Cytogenetic analyses have revealed consistent rearrangement of chromosome band 11q12, strongly suggesting that this region harbors a gene of pathogenetic importance. To identify the target gene of the 11q12 rearrangements, we analyzed six cases diagnosed as DF using chromosome banding, fluorescence in situ hybridization (FISH), single-nucleotide polymorphism array and gene expression approaches. Different structural rearrangements involving 11q12 were found in five of the six cases. Metaphase FISH analyses in two of them mapped the 11q12 breakpoints to an ∼20-kb region, harboring FOSL1. Global gene expression profiling followed by quantitative real-time PCR showed that FOSL1 was expressed at higher levels in DF with 11q12 rearrangements than in desmoid-type fibromatoses. Furthermore, FOSL1 was not upregulated in the single case of DF that did not show cytogenetic involvement of 11q12; instead this tumor was found to display a hemizygous loss on 5q, including the APC (adenomatous polyposis coli) locus, raising the possibility that it actually was a misdiagnosed Gardner fibroma. 5'RACE-PCR in two 11q12-positive DF did not identify any fusion transcripts. Thus, in agreement with the finding at chromosome banding analysis that varying translocation partners are involved in the 11q12 rearrangement, the molecular data suggest that the functional outcome of the 11q12 rearrangements is deregulated expression of FOSL1.Laboratory Investigation advance online publication, 12 March 2012; doi:10.1038/labinvest.2012.46.
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| 44. |
- Marcusson, Jan, et al.
(author)
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Proactive healthcare for frail elderly persons : study protocol for a prospective controlled primary care intervention in Sweden
- 2019
-
In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:5
-
Journal article (peer-reviewed)abstract
- Introduction The provision of healthcare services is not dedicated to promoting maintenance of function and does not target frail older persons at high risk of the main causes of morbidity and mortality. The aim of this study is to evaluate the effects of a proactive medical and social intervention in comparison with conventional care on a group of persons aged 75 and older selected by statistical prediction.Methods and analysis In a pragmatic multicentre primary care setting (n=1600), a prediction model to find elderly (75+) persons at high risk of complex medical care or hospitalisation is used, followed by proactive medical and social care, in comparison with usual care. The study started in April 2017 with a run-in period until December 2017, followed by a 2-year continued intervention phase that will continue until the end of December 2019. The intervention includes several tools (multiprofessional team for rehabilitation, social support, medical care home visits and telephone support). Primary outcome measures are healthcare cost, number of hospital care episodes, hospital care days and mortality. Secondary outcome measures are number of outpatient visits, cost of social care and informal care, number of prescribed drugs, health-related quality of life, cost-effectiveness, sense of security, functional status and ability. We also study the care of elderly persons in a broader sense, by covering the perspectives of the patients, the professional staff and the management, and on a political level, by using semistructured interviews, qualitative methods and a questionnaire.Ethics and dissemination Approved by the regional ethical review board in Linköping (Dnr 2016/347-31). The results will be presented in scientific journals and scientific meetings during 2019–2022 and are planned to be used for the development of future care models.
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| 45. |
- Mohajeri, Arezoo, et al.
(author)
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Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor.
- 2013
-
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 52:10, s. 873-886
-
Journal article (peer-reviewed)abstract
- Solitary fibrous tumor (SFT) is a mesenchymal neoplasm displaying variable morphologic and clinical features. To identify pathogenetically important genetic rearrangements, 44 SFTs were analyzed using a variety of techniques. Chromosome banding and fluorescence in situ hybridization (FISH) showed recurrent breakpoints in 12q13, clustering near the NAB2 and STAT6 genes, and single nucleotide polymorphism array analysis disclosed frequent deletions affecting STAT6. Quantitative real-time PCR revealed high expression levels of the 5'-end of NAB2 and the 3'-end of STAT6, which at deep sequencing of enriched DNA corresponded to NAB2/STAT6 fusions. Subsequent reverse-transcriptase PCR (RT-PCR) analysis identified a NAB2/STAT6 fusion in 37/41 cases, confirming that this fusion gene underlies the pathogenesis of SFT. The hypothesis that the NAB2/STAT6 fusions will result in altered properties of the transcriptional co-repressor NAB2 - a key regulator of the early growth response 1 (EGR1) transcription factor - was corroborated by global gene expression analysis; SFTs showed deregulated expression of EGR1 target genes, as well as of other, developmentally important genes. We also identified several nonrandom secondary changes, notably loss of material from 13q and 14q. As neither chromosome banding nor FISH analysis identify more than a minor fraction of the fusion-positive cases, and because multiple primer combinations are required to identify all possible fusion transcripts by RT-PCR, alternative diagnostic markers might instead be found among deregulated genes identified at global gene expression analysis. Indeed, using immunohistochemistry on tissue microarrays, the top up-regulated gene, GRIA2, was found to be differentially expressed also at the protein level. © 2013 Wiley Periodicals, Inc.
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| 46. |
- Nord, Andreas, et al.
(author)
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Female zebra finches compromise clutch temperature in energetically demanding incubation conditions
- 2010
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In: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 24:5, s. 1031-1036
-
Journal article (peer-reviewed)abstract
- P>1. Avian embryos depend on the incubating parent to provide a thermal environment suitable for embryogenesis, but as the maintenance of optimal incubation temperatures is energetically costly, an incubating bird often must trade off embryonic investment against self-maintenance. 2. We manipulated the energetic cost of incubation in female zebra finches (Taeniopygia guttata Vieillot) by varying ambient temperature and clutch size during nocturnal incubation and recorded the corresponding effects on incubation metabolic rate and clutch temperature. 3. Females increased their night-time incubation metabolic rate more than twofold when incubating at 10 degrees C compared to when incubating close to thermoneutrality (28 degrees C). Furthermore, clutch enlargement caused females to elevate their metabolic rate with 2 center dot 8% per additional egg added to the clutch. 4. However, despite spending more energy, females did not fully cover the increased costs of incubation, because clutch temperature decreased with decreasing ambient temperature and increasing clutch size. 5. These findings suggest that parental investment in incubation can be energetically constrained and sometimes result in clutch temperatures below the optimal level for embryonic development, at least during nocturnal incubation.
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| 47. |
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| 48. |
- Nord, Andreas, et al.
(author)
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Patterns and dynamics of rest-phase hypothermia in wild and captive blue tits during winter.
- 2009
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In: Journal of Comparative Physiology B. - : Springer Science and Business Media LLC. - 0174-1578 .- 1432-136X. ; 179, s. 737-745
-
Journal article (peer-reviewed)abstract
- We evaluated biotic and abiotic predictors of rest-phase hypothermia in wintering blue tits (Cyanistes caeruleus) and also assessed how food availability influences nightly thermoregulation. On any given night, captive blue tits (with unrestricted access to food) remained largely homeothermic, whereas free-ranging birds decreased their body temperature (T (b)) by about 5 degrees C. This was not an effect of increased stress in the aviary as we found no difference in circulating corticosterone between groups. Nocturnal T (b) in free-ranging birds varied with ambient temperature, date and time. Conversely, T (b) in captive birds could not be explained by climatic or temporal factors, but differed slightly between the sexes. We argue that the degree of hypothermia is controlled predominantly by birds' ability to obtain sufficient energy reserves during the day. However, environmental factors became increasingly important for thermoregulation when resources were limited. Moreover, as birds did not enter hypothermia in captivity when food was abundant, we suggest that this strategy has associated costs and hence is avoided whenever resource levels permit.
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| 49. |
- Nord, Christoffer, et al.
(author)
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Biochemical profiling of diabetes disease progression by multivariate vibrational microspectroscopy of the pancreas
- 2017
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 6646-
-
Journal article (peer-reviewed)abstract
- Despite the dramatic increase in the prevalence of diabetes, techniques for in situ studies of the underlying pancreatic biochemistry are lacking. Such methods would facilitate obtaining mechanistic understanding of diabetes pathophysiology and aid in prognostic and/or diagnostic assessments. In this report we demonstrate how a multivariate imaging approach (orthogonal projections to latent structures - discriminant analysis) can be applied to generate full vibrational microspectroscopic profiles of pancreatic tissues. These profiles enable extraction of known and previously unrecorded biochemical alterations in models of diabetes, and allow for classification of the investigated tissue with regards to tissue type, strain and stage of disease progression. Most significantly, the approach provided evidence for dramatic alterations of the pancreatic biochemistry at the initial onset of immune-infiltration in the Non Obese Diabetic model for type 1 diabetes. Further, it enabled detection of a previously undocumented accumulation of collagen fibrils in the leptin deficient ob/ob mouse islets. By generating high quality spectral profiles through the tissue capsule of hydrated human pancreata and by in vivo Raman imaging of pancreatic islets transplanted to the anterior chamber of the eye, we provide critical feasibility studies for the translation of this technique to diagnostic assessments of pancreatic biochemistry in vivo.
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| 50. |
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