| 1. |
- Engert, Andreas, et al.
(author)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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In: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Journal article (peer-reviewed)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 4. |
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| 5. |
- Olsson, André, et al.
(author)
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Transcriptional repression by leukaemia-associated ETO family members can be independent of oligomerization and coexpressed hSIN3B and N-CoR.
- 2008
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399. ; 1779:10, s. 590-598
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Journal article (peer-reviewed)abstract
- The leukaemia-associated eight-twenty-one (ETO) family members ETO, MTG16 (Myeloid Translocation Gene on chromosome 16) and MTGR1 (Myeloid Transforming Gene-Related protein1) are putative transcriptional repressor proteins, which form complexes with coregulatory nuclear corepressors such as SIN3 (SWI-Independent) and N-CoR (Nuclear receptor Co Repressor). In acute myeloid leukaemia (AML), fusion proteins involving the transcription factor AML1 and corepressors ETO or MTG16 are recurrently found. We investigated transcriptional repression by the ETO family members ETO and MTG16 with attention to the conserved Nervy Homology Regions (NHRs) and the interacting corepressors human SIN3B (hSIN3B) and N-CoR. Transcriptional repression was examined in a cell line by a GAL4-thymidine kinase luciferase reporter to which the corepressors were tethered through a binding domain. ETO- and MTG16-mediated repression was found to be independent of deletion of the oligomerization NHR2, but deletion of NHR4 and in particular combined deletion of NHR2 and NHR4 lowered the capacity for repression. An interaction was observed between the corepressors hSIN3B and N-CoR and these two proteins cooperated for transcriptional repression independent of co-transfected ETO and MTG16. Transcriptional repression mediated by ETO and MTG16 was only slightly strengthened by coexpression of hSIN3B or N-CoR and was dependent on HDAC activity. Our data indicate that ETO family member-mediated oligomerization and repression can be distinct events and that interaction between ETO family members and hSIN3B or N-CoR may not necessarily strengthen transcriptional repression.
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| 6. |
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| 7. |
- Rondin Lindberg, Sofia, et al.
(author)
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Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins.
- 2003
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 71:6, s. 439-447
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Journal article (peer-reviewed)abstract
- The eight-twenty-one (ETO) homologues, represented by ETO, myeloid transforming gene-related protein 1 (MTGR1) and myeloid transforming gene chromosome 16 (MTG16), are nuclear repressor proteins. ETO is part of the fusion protein acute myeloid leukaemia (AML)1-ETO, resulting from the translocation (8;21). Similarly, MTG16 is disrupted to become part of AML1/MTG16 in t(16;21). The aberrant expression of these chimeras could affect interplay between ETO homologues and contribute to the leukaemogenic process. We investigated possible interactions between the ETO homologues. Ectopic co-expression in COS-cells resulted in heterodimerisation of the various ETO homologues suggesting that they may co-operate. Similarly, the chimeric oncoprotein AML1-ETO interacted with both MTGR1 and MTG16. However, results from cell lines endogenously expressing more than one ETO homologue did not demonstrate co-precipitation. Results from IP-Western and size determination by gel filtration of deletion mutants expressed in COS-cells, indicated an important role of the HHR domain for oligomerisation. A role was also suggested for the Nervy domain in the homologue interactions. Our results suggest that ETO homologues can interact with each other as well as with AML1-ETO, although it is unclear as to what extent these interactions occur in vivo.
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| 8. |
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| 9. |
- Adewumi, Oluseun, et al.
(author)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Journal article (peer-reviewed)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 10. |
- Alström, Per, Professor, et al.
(author)
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Systematics of the avian family Alaudidae using multilocus and genomic data
- 2023
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In: Avian Research. - : Elsevier BV. - 2053-7166. ; 14
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Journal article (peer-reviewed)abstract
- The family Alaudidae, larks, comprises 93–100 species (depending on taxonomy) that are widely distributed across Africa and Eurasia, with single species extending their ranges to North and northernmost South America and Australia. A decade-old molecular phylogeny, comprising ∼80% of the species, revealed multiple cases of parallel evolution and large variation in rates of morphological evolution, which had misled taxonomists into creating many non-monophyletic genera. Here, we reconstruct the phylogeny of the larks, using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species (in total 133 taxa; not all loci available for all species). We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling (in total 51 samples of 44 taxa across 40 species). Our results confirm the previous findings of rampant morphological convergence and divergence, and reveal new cases of paraphyletic genera. We propose a new subfamily classification, and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae. Our study supports recently proposed species splits as well as some recent lumps, while also questioning some of the latter. This comprehensive phylogeny will form an important basis for future studies, such as comparative studies of lark natural history, ecology, evolution and conservation.
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| 11. |
- André, Alann, 1980, et al.
(author)
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Compression failure mechanism in small-scale wood specimens reinforced with CFRP: An experimental study
- 2013
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In: Construction and Building Materials. - : Elsevier BV. - 0950-0618 .- 1879-0526. ; 41, s. 790-800
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Journal article (peer-reviewed)abstract
- The optimal use of Carbon Fibre Reinforced Polymer (CFRP) when strengthening timber beams loaded in bending involves considering placing the reinforcement on both the tension and the compression side, in order to utilise the ductile compression failure of the wood to the full. In this respect, a knowledge and understanding of the compression failure mechanism of the timber/CFRP system becomes a point of paramount importance. However, no testing method specific to the compression loading of small wood specimens reinforced with CFRP is currently available. This investigation focuses on the experimental developments of the geometry and test set-up necessary in order to determine the compression failure mechanism of small wood block specimens reinforced With CFRP loaded in compression parallel to the grain. The method is based on an existing testing method for unreinforced wood specimens. The Digital Image Correlation (DIC) method is used to monitor deformation during experim!
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| 12. |
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| 13. |
- Axfors, Cathrine, et al.
(author)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 14. |
- Ayoglu, Burcu, et al.
(author)
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Anoctamin 2 identified as an autoimmune target in multiple sclerosis
- 2016
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences of the USA. - 0027-8424 .- 1091-6490. ; 113:8, s. 2188-2193
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Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.
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| 15. |
- Azevedo, Flavio, et al.
(author)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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In: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Journal article (peer-reviewed)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 16. |
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| 17. |
- Beecham, Ashley H, et al.
(author)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Journal article (peer-reviewed)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 18. |
- Berglund, Rasmus, et al.
(author)
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Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation
- 2020
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In: Science Immunology. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 2470-9468.
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Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.
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| 19. |
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| 20. |
- Bronge, Mattias, et al.
(author)
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Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis
- 2022
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:17
-
Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-gamma responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4(+) and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.
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| 21. |
- Carlsson, Michael, et al.
(author)
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Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.
- 2011
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10
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Journal article (peer-reviewed)abstract
- Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.
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| 22. |
- Costa, Sergio, 1987, et al.
(author)
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Improvement and validation of a physically based model for the shear and transverse crushing of orthotropic composites
- 2019
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In: Journal of Composite Materials. - : SAGE Publications. - 1530-793X .- 0021-9983. ; 53:12, s. 1681-1696
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Journal article (peer-reviewed)abstract
- This paper details a complete crush model for composite materials with focus on shear dominated crushing under a three-dimensional stress state. The damage evolution laws and final failure strain conditions are based on data extracted from shear experiments. The main advantages of the current model include the following: no need to measure the fracture toughness in shear and transverse compression, mesh objectivity without the need for a regular mesh and finite element characteristic length, a pressure dependency of the nonlinear shear response, accounting for load reversal and some orthotropic effects (making the model suitable for noncrimp fabric composites). The model is validated against a range of relevant experiments, namely a through-the-thickness compression specimen and a flat crush coupon with the fibres oriented at 45° and 90° to the load. Damage growth mechanisms, orientation of the fracture plane, nonlinear evolution of Poisson's ratio and energy absorption are accurately predicted.
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| 23. |
- Costa, Sergio, et al.
(author)
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Numerical validation of an improved model for the shearing and transverse crushingof orthotropic composites
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Other publication (other academic/artistic)abstract
- This paper details a complete crush model for composite materials with focus on shear dominated crushing under a3D stress state. The damage evolution laws and nal failure strain conditions are based on data extracted from shearexperiments. The main advantages of the current model are: no need to measure the fracture toughness in shear andtransverse compression, mesh objectivity without the need for a regular mesh and nite element characteristic length, apressure dependency of the shear response, account for load reversal and for some orthotropic eects (making the modelsuitable for Non-Crimp Fabric composites). The model is validated against a range of relevant experiments, namely athrough-the-thickness compression specimen and a at crush coupon with the bres oriented at 45 and 90 degrees to theload. Damage growth mechanisms, orientation of the fracture plane, nonlinear evolution of Poisson's ratio and energyabsorption are accurately predicted.
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| 24. |
- Costa, Sergio, 1987, et al.
(author)
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Validation of a novel model for the compressive response of FRP: Numerical simulation
- 2017
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In: ICCM International Conferences on Composite Materials. ; 2017-August
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Conference paper (peer-reviewed)abstract
- A progressive damage model for matrix compression is complemented with matrix tension in a physically based manner. The interaction of damage mechanisms undergoes a preliminary validation using single elements. The crushing response is validated with two different flat specimens with the fibres oriented transversely and at 45 degrees to the load. The model combines friction with damage to model the shear response accurately, which is necessary for reliable crush simulations. The behaviour in tension is history dependent, i.e. the model accounts for the stiffness reduction and strength to carry load in tension when previously damaged occurs in compression. The validation is performed against different tests showing the reliability of the model for different fibre orientation, specimen geometry and multiaxial loading scenarios. The crush response is well captured as well as the geometry and location of the different damage mechanisms.
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| 25. |
- Eriksson, Anders, et al.
(author)
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RPC-LAP : The Rosetta Langmuir probe instrument
- 2007
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 128:04-jan, s. 729-744
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Research review (peer-reviewed)abstract
- The Rosetta dual Langmuir probe instrument, LAP, utilizes the multiple powers of a pair of spherical Langmuir probes for measurements of basic plasma parameters with the aim of providing detailed knowledge of the outgassing, ionization, and subsequent plasma processes around the Rosetta target comet. The fundamental plasma properties to be studied are the plasma density, the electron temperature, and the plasma flow velocity. However, study of electric fields up to 8 kHz, plasma density fluctuations, spacecraft potential, integrated UV flux, and dust impacts is also possible. LAP is fully integrated in the Rosetta Plasma Consortium (RPC), the instruments of which together provide a comprehensive characterization of the cometary plasma.
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| 26. |
- Goedecke, Julia H., et al.
(author)
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Waist circumference thresholds predicting incident dysglycaemia and type 2 diabetes in Black African men and women
- 2022
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In: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 24:5, s. 918-927
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Journal article (peer-reviewed)abstract
- Aims: To determine the waist circumference (WC) thresholds for the prediction of incident dysglycaemia and type 2 diabetes (T2D) in Black South African (SA) men and women and to compare these to the advocated International Diabetes Federation (IDF) Europid thresholds.Materials and Methods: In this prospective study, Black SA men (n = 502) and women (n = 527) from the Middle-aged Sowetan Cohort study who had normal or impaired fasting glucose at baseline (2011-2015) were followed up until 2017 to 2018. Baseline measurements included anthropometry, blood pressure and fasting glucose, HDL cholesterol and triglyceride concentrations. At follow-up, glucose tolerance was assessed using an oral glucose tolerance test. The Youden index was used to determine the optimal threshold of WC to predict incident dysglycaemia and T2D.Results: In men, the optimal WC threshold was 96.8 cm for both dysglycaemia and T2D (sensitivity: 56% and 70%; specificity: 74% and 70%, respectively), and had higher specificity (P < 0.001) than the IDF threshold of 94 cm. In women, the optimal WC threshold for incident dysglycaemia was 91.8 cm (sensitivity 86%, specificity 37%) and for T2D it was 95.8 cm (sensitivity 85%, specificity 45%), which had lower sensitivity, but higher specificity to predict incident dysglycaemia and T2D than the IDF threshold of 80 cm (sensitivity: 97% and 100%; specificity: 12% and 11%, respectively)).Conclusions: We show for the first time using prospective cohort data from Africa that the IDF Europid WC thresholds are not appropriate for an African population, and show that African-specific WC thresholds perform better than the IDF Europid thresholds to predict incident dysglycaemia and T2D.
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| 27. |
- Helland, Christian, et al.
(author)
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Training Strategies to Improve Muscle Power : Is Olympic-style Weightlifting Relevant?
- 2017
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In: Medicine & Science in Sports & Exercise. - Philadelphia, PA : Lippincott Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 49:4, s. 736-745
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Journal article (peer-reviewed)abstract
- INTRODUCTION: This efficacy study investigated the effects of (1) Olympic-style weightlifting (OWL), (2) motorized strength and power training (MSPT), and (3) free weight strength and power training (FSPT) on muscle power.METHODS: Thirty-nine young athletes (20±3 yr.; ice hockey, volleyball and badminton) were randomized into the three training groups. All groups participated in 2-3 sessions/week for 8 weeks. The MSPT and FSPT groups trained using squats (two legs and single leg) with high force and high power, while the OWL group trained using clean and snatch exercises. MSPT was conducted as slow-speed isokinetic strength training and isotonic power training with augmented eccentric load, controlled by a computerized robotic engine system. FSPT used free weights. The training volume (sum of repetitions x kg) was similar between all three groups. Vertical jumping capabilities were assessed by countermovement jump (CMJ), squat jump (SJ), drop jump (DJ), and loaded CMJs (10-80 kg). Sprinting capacity was assessed in a 30 m sprint. Secondary variables were squat 1-repetition-maximum, body composition and quadriceps thickness and architecture.RESULTS: OWL resulted in trivial improvements, and inferior gains compared to FSPT and MSPT for CMJ, SJ, and DJ. MSPT demonstrated small, but robust effects on SJ, DJ and loaded CMJs (3-12%). MSPT was superior to FSPT in improving 30 m sprint performance. FSPT and MSPT, but not OWL, demonstrated increased thickness in the vastus lateralis and rectus femoris (4-7%).CONCLUSION: MSPT was time-efficient and equally or more effective than FSPT training in improving vertical jumping and sprinting performance. OWL was generally ineffective and inferior to the two other interventions. Copyright © 2016 by the American College of Sports Medicine.
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| 28. |
- Holmes, Michael V., et al.
(author)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Journal article (peer-reviewed)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 29. |
- Keogan, Katharine, et al.
(author)
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Global phenological insensitivity to shifting ocean temperatures among seabirds
- 2018
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In: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:4, s. 313-318
-
Journal article (peer-reviewed)abstract
- Reproductive timing in many taxa plays a key role in determining breeding productivity(1), and is often sensitive to climatic conditions(2). Current climate change may alter the timing of breeding at different rates across trophic levels, potentially resulting in temporal mismatch between the resource requirements of predators and their prey(3). This is of particular concern for higher-trophic-level organisms, whose longer generation times confer a lower rate of evolutionary rescue than primary producers or consumers(4). However, the disconnection between studies of ecological change in marine systems makes it difficult to detect general changes in the timing of reproduction(5). Here, we use a comprehensive meta-analysis of 209 phenological time series from 145 breeding populations to show that, on average, seabird populations worldwide have not adjusted their breeding seasons over time (-0.020 days yr(-1)) or in response to sea surface temperature (SST) (-0.272 days degrees C-1) between 1952 and 2015. However, marked between-year variation in timing observed in resident species and some Pelecaniformes and Suliformes (cormorants, gannets and boobies) may imply that timing, in some cases, is affected by unmeasured environmental conditions. This limited temperature-mediated plasticity of reproductive timing in seabirds potentially makes these top predators highly vulnerable to future mismatch with lower-trophic-level resources(2).
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| 30. |
- Kufe, Clement N., et al.
(author)
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Increased risk for type 2 diabetes in relation to adiposity in middle-aged Black South African men compared to women
- 2022
-
In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 186:5, s. 523-533
-
Journal article (peer-reviewed)abstract
- Aims: Despite a higher prevalence of overweight/obesity in Black South African women compared to men, the prevalence of type 2 diabetes (T2D) does not differ. We explored if this could be due to sex differences in insulin sensitivity, clearance and/or beta-cell function and also sex-specific associations with total and regional adiposity.Methods: This cross-sectional study included 804 Black South African men (n = 388) and women (n = 416). Dual-energy X-ray absorptiometry was used to measure total and regional adiposity. Insulin sensitivity (Matsuda index), secretion (C-peptide index) and clearance (C-peptide/insulin ratio) were estimated from an oral glucose tolerance test.Results: After adjusting for sex differences in the fat mass index, men were less insulin sensitive and had lower beta-cell function than women (P < 0.001), with the strength of the associations with measures of total and central adiposity being greater in men than women (P < 0.001 for interactions). Further, the association between total adiposity and T2D risk was also greater in men than women (relative risk ratio (95% CI): 2.05 (1.42-2.96), P < 0.001 vs 1.38 (1.03-1.85), P = 0.031).Conclusion: With increasing adiposity, particularly increased centralisation of body fat linked to decreased insulin sensitivity and beta-cell function, Black African men are at greater risk for T2D than their female counterparts.
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| 31. |
- Kufe, Nyuyki Clement, et al.
(author)
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Protocol for systematic review and meta-analysis of sex hormones and diabetes risk in ageing men and women of African ancestry
- 2019
-
In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:1
-
Research review (peer-reviewed)abstract
- Aim: To present the protocol of a systematic review and meta-analysis of the available evidence examining the association between sex hormones and type 2 diabetes risk in ageing men and women of African descent.Methods: We shall conduct a comprehensive search of published studies that examined the association between sex hormones and type 2 diabetes risk in men and women aged ≥40 years from 01/01/1980 to 31/03/2018 with no language restriction. Databases to be searched include: PubMed, Scopus, Cochrane Library, Cumulative Index to Nursing and Allied Health, ISI Web of Science, Clinical Trial registries, Google Scholar and institutional websites such as the WHO, American Diabetes Association, International Diabetes Federation, World Diabetes Foundation, European Association for the Study of Diabetes, African Journal Online and ProQuest databases. This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Independent screening for eligible studies using defined criteria and data extraction, will be completed in duplicate. Discrepancies will be resolved by consensus or consultation with a third researcher. Risk of bias of included studies will be assessed by the appropriate Cochrane risk of bias tool. The overall association estimates will be pooled using appropriate meta-analytic techniques. Heterogeneity will be assessed using Cochrane Q statistic and the inconsistency index (I2). The random effects model will be used to calculate a pooled estimate.Ethics and dissemination: No ethics clearance is required as no primary data will be collected. The systematic review and meta-analysis are part of a PhD project at WITS University (Johannesburg, South Africa) and results will be presented at conferences and published in a peer-review journal. The results will guide future population specific interventions.
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| 32. |
- Kukanja, Petra, et al.
(author)
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Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology
- 2024
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In: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 187:8, s. 1990-2009
-
Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single -cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the cellular dynamics of MS by modeling temporal and regional rates of disease progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing single -cell spatial expression profiling using in situ sequencing (ISS), we annotated disease neighborhoods and found centrifugal evolution of active lesions. We demonstrated that disease -associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. Single -cell spatial mapping of human archival MS spinal cords confirmed the differential distribution of homeostatic and DA-glia, enabled deconvolution of active and inactive lesions into sub -compartments, and identified new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single -cell resolution, our study unveils the intricate cellular dynamics underlying MS.
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| 33. |
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| 34. |
- Lattanzi, Veronica, et al.
(author)
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Amyloid β 42 fibril structure based on small-angle scattering
- 2021
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 118:48
-
Journal article (peer-reviewed)abstract
- Amyloid fibrils are associated with a number of neurodegenerative diseases, including fibrils of amyloid β42 peptide (Aβ42) in Alzheimer's disease. These fibrils are a source of toxicity to neuronal cells through surface-catalyzed generation of toxic oligomers. Detailed knowledge of the fibril structure may thus facilitate therapeutic development. We use small-angle scattering to provide information on the fibril cross-section dimension and shape for Aβ42 fibrils prepared in aqueous phosphate buffer at pH = 7.4 and pH 8.0 under quiescent conditions at 37°C from pure recombinant Aβ42 peptide. Fitting the data using a continuum model reveals an elliptical cross-section and a peptide mass-per-unit length compatible with two filaments of two monomers, four monomers per plane. To provide a more detailed atomistic model, the data were fitted using as a starting state a high-resolution structure of the two-monomer arrangement in filaments from solid-state NMR (Protein Data Bank ID 5kk3). First, a twofold symmetric model including residues 11 to 42 of two monomers in the filament was optimized in terms of twist angle and local packing using Rosetta. A two-filament model was then built and optimized through fitting to the scattering data allowing the two N-termini in each filament to take different conformations, with the same conformation in each of the two filaments. This provides an atomistic model of the fibril with twofold rotation symmetry around the fibril axis. Intriguingly, no polydispersity as regards the number of filaments was observed in our system over separate samples, suggesting that the two-filament arrangement represents a free energy minimum for the Aβ42 fibril.
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| 35. |
- Lewin, Erik, et al.
(author)
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Industrialisation Study of Nanocomposite nc-TiC/a-C Coatings for Electrical Contact Applications
- 2009
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In: Plasma Processes and Polymers. - : WILEY-VCH Verlag GmbH & Co. - 1612-8850. ; 6:S1, s. S928-S934
-
Journal article (peer-reviewed)abstract
- Nanocomposite nc-TiC/a-C coatings were prepared by non-reactive magnetron sputtering in industrial scale equipment, under varying deposition conditions in order to investigate upscaling and possible industrialisation. The coatings were found to have similar microstructure and performance compared to previous laboratory scale experiments. The samples were characterised with XRD, XPS and SEM as well with ball-on-disc, nanoindentation and electrical measurements. Coatings containing a small fraction of a-C matrix phase were found to have promising both electrical properties (rho < 400 mu Omega cm and contact resistances down to 0.34 m Omega at 40 N) and tribological properties (f < 0.3 for 10 000 laps).
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| 36. |
- Lindahl, Hannes, et al.
(author)
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IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis
- 2019
-
In: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 203:4, s. 888-898
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies have mapped the specific sequence variants that predispose for multiple sclerosis (MS). The pathogenic mechanisms that underlie these associations could be leveraged to develop safer and more effective MS treatments but are still poorly understood. In this article, we study the genetic risk variant rs17066096 and the candidate gene that encodes IL-22 binding protein (IL-22BP), an antagonist molecule of the cytokine IL-22. We show that monocytes from carriers of the risk genotype of rs17066096 express more IL-22BP in vitro and cerebrospinal fluid levels of IL-22BP correlate with MS lesion load on magnetic resonance imaging. We confirm the pathogenicity of IL-22BP in both rat and mouse models of MS and go on to suggest a pathogenic mechanism involving lack of IL-22-mediated inhibition of T cell-derived IFN-gamma expression. Our results demonstrate a pathogenic role of IL-22BP in three species with a potential mechanism of action involving T cell polarization, suggesting a therapeutic potential of IL-22 in the context of MS.
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| 37. |
- Lindgren, Nils, et al.
(author)
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Updating of forest stand data by using recent digital photogrammetry in combination with older airborne laser scanning data
- 2021
-
In: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 36, s. 401-407
-
Journal article (peer-reviewed)abstract
- Accurate and up-to-date data about growing stock volume are essential for forest management planning. Airborne Laser Scanning (ALS) is known for producing accurate wall-to-wall predictions but the data are at present collected at long time intervals. Digital Photogrammetry (DP) is cheaper and often more frequently available but known to be less accurate. This study investigates the potential of using contemporary DP data together with older ALS data and compares this with the case when only old ALS data are trained with recent field data. Combining ALS data from 2010 to 2011 with DP data from 2015, both trained with National Forest Inventory (NFI) field plot data from 2015, improved predictions of growing stock volume. Validation using data from 100 stands inventoried in 2015 gave an RMSE of 24.3% utilizing both old ALS data and recent DP data, 26.0% for old ALS only and 24.9% for recent DP only. If information about management actions were assumed available, combining old ALS and recent DP gave RMSE of 23.0%, only ALS 23.3% and only DP 23.8%.
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| 38. |
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| 39. |
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| 40. |
- McElroy, Mark, et al.
(author)
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Use of enriched shell elements compared to solid elements for modelling delamination growth during impact on composites
- 2021
-
In: Composite structures. - : Elsevier Ltd. - 0263-8223 .- 1879-1085. ; 269
-
Journal article (peer-reviewed)abstract
- Simulation of damage in composite laminates using currently available three-dimensional finite element tools is computationally demanding often to the point that analysis is not practical. This paper presents an enriched shell element that can provide a computationally efficient means to simulate low-velocity impact damage in a composite. The enriched element uses the Floating Node Method and a damage algorithm based on the Virtual Crack Closure Technique that is capable of simulating progressive damage growth consisting of delamination and delamination-migrations from ply to ply during a dynamic impact load. This paper presents results from the shell model in a test-analysis correlation for impact testing of 7-ply and 56-ply laminates. Analysis results from a separate high-fidelity three-dimensional finite element analysis are included also for comparison in the case of the 7-ply laminate, but not in the case the 56-ply laminate due to excessive computational demand. This paper serves as the first application of both models in low-velocity impact simulation. The shell model is considerably more computationally efficient than the high-fidelity model by at least an order of magnitude and is shown to produce results, while not as accurate as the high-fidelity model, potentially sufficiently accurate for a wide range of engineering applications including structural design and rapid prototype assessments.
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| 41. |
- Mendham, Amy E., et al.
(author)
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Targeted proteomics identifies potential biomarkers of dysglycaemia, beta cell function and insulin sensitivity in Black African men and women
- 2023
-
In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66, s. 174-189
-
Journal article (peer-reviewed)abstract
- Aims/hypothesis: Using a targeted proteomics approach, we aimed to identify and validate circulating proteins associated with impaired glucose metabolism (IGM) and type 2 diabetes in a Black South African cohort. In addition, we assessed sex-specific associations between the validated proteins and pathophysiological pathways of type 2 diabetes.Methods: This cross-sectional study included Black South African men (n=380) and women (n=375) who were part of the Middle-Aged Soweto Cohort (MASC). Dual-energy x-ray absorptiometry was used to determine fat mass and visceral adipose tissue, and fasting venous blood samples were collected for analysis of glucose, insulin and C-peptide and for targeted proteomics, measuring a total of 184 pre-selected protein biomarkers. An OGTT was performed on participants without diabetes, and peripheral insulin sensitivity (Matsuda index), HOMA-IR, basal insulin clearance, insulin secretion (C-peptide index) and beta cell function (disposition index) were estimated. Participants were classified as having normal glucose tolerance (NGT; n=546), IGM (n=116) or type 2 diabetes (n=93). Proteins associated with dysglycaemia (IGM or type 2 diabetes) in the MASC were validated in the Swedish EpiHealth cohort (NGT, n=1706; impaired fasting glucose, n=550; type 2 diabetes, n=210).Results: We identified 73 proteins associated with dysglycaemia in the MASC, of which 34 were validated in the EpiHealth cohort. Among these validated proteins, 11 were associated with various measures of insulin dynamics, with the largest number of proteins being associated with HOMA-IR. In sex-specific analyses, IGF-binding protein 2 (IGFBP2) was associated with lower HOMA-IR in women (coefficient –0.35; 95% CI –0.44, –0.25) and men (coefficient –0.09; 95% CI –0.15, –0.03). Metalloproteinase inhibitor 4 (TIMP4) was associated with higher insulin secretion (coefficient 0.05; 95% CI 0.001, 0.11; p for interaction=0.025) and beta cell function (coefficient 0.06; 95% CI 0.02, 0.09; p for interaction=0.013) in women only. In contrast, a stronger positive association between IGFBP2 and insulin sensitivity determined using an OGTT (coefficient 0.38; 95% CI 0.27, 0.49) was observed in men (p for interaction=0.004). A posteriori analysis showed that the associations between TIMP4 and insulin dynamics were not mediated by adiposity. In contrast, most of the associations between IGFBP2 and insulin dynamics, except for insulin secretion, were mediated by either fat mass index or visceral adipose tissue in men and women. Fat mass index was the strongest mediator between IGFBP2 and insulin sensitivity (total effect mediated 40.7%; 95% CI 37.0, 43.6) and IGFBP2 and HOMA-IR (total effect mediated 39.1%; 95% CI 31.1, 43.5) in men.Conclusions/interpretation: We validated 34 proteins that were associated with type 2 diabetes, of which 11 were associated with measures of type 2 diabetes pathophysiology such as peripheral insulin sensitivity and beta cell function. This study highlights biomarkers that are similar between cohorts of different ancestry, with different lifestyles and sociodemographic profiles. The African-specific biomarkers identified require validation in African cohorts to identify risk markers and increase our understanding of the pathophysiology of type 2 diabetes in African populations.
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| 42. |
- Mtintsilana, Asanda, et al.
(author)
-
Adiposity Mediates the Association between the Dietary Inflammatory Index and Markers of Type 2 Diabetes Risk in Middle-Aged Black South African Women
- 2019
-
In: Nutrients. - : MDPI. - 2072-6643. ; 11:6
-
Journal article (peer-reviewed)abstract
- The dietary inflammatory index (DII®), a validated tool used to measure the inflammatory potential of the diet, has been associated with metabolic disorders in various settings, but not in African populations. The aim of this study was to investigate whether the DII is associated with markers of type 2 diabetes (T2D) risk, and if this association is mediated by adiposity and/or low-grade inflammation, in black South Africa women. Energy-adjusted-DII (E-DII) scores were calculated in 190 women (median age, 53 years) from the Birth-to-Twenty plus cohort using a validated food frequency questionnaire. Fasting glucose, insulin, HbA1c, and inflammatory cytokines were measured, and an oral glucose tolerance test performed. Basic anthropometry and dual-energy x-ray absorptiometry-derived body fat, including estimate of visceral adipose tissue (VAT) area, were measured. E-DII scores were associated with all markers of T2D risk, namely, fasting glucose and insulin, HbA1c, HOMA2-IR, two-hour glucose and Matsuda index (all p < 0.05). After adjusting for age, measures of adiposity, but not inflammatory cytokines, mediated the association between E-DII and markers of T2D risk (p < 0.05). Measures of central obesity had proportionally higher (range: 23.5–100%) mediation effects than total obesity (range: 10–60%). The E-DII is associated with T2D risk through obesity, in particular central obesity, among black middle-aged South African women.
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| 43. |
- Næss, Sigrid, et al.
(author)
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Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
- 2014
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
-
Journal article (peer-reviewed)abstract
- Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
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| 44. |
- Olsson, André
(author)
-
The role of the leukemia-associated ETO homologue repressors in hematopoiesis
- 2006
-
Doctoral thesis (other academic/artistic)abstract
- The fusion protein AML1-ETO is observed in acute myeloid patients with the chromosomal translocation t(8;21). Cells with this chimeric protein have impaired granulocytic and erythroid differentiation with accumulation of myeloblasts. The transcriptional co-repressor ETO (Eight Twenty One) was identified from the cloning of AML1-ETO. Subsequently, MTGR1 (Myeloid Translocation Gene-Related protein 1) and MTG16 (Myeloid Translocation Gene on chromosome 16) were found to be homologues to ETO, all these proteins being transcriptional co-repressors present in complexes together with other co-repressors such as SIN3, N-CoR and SMRT, and histone deacetylases. The objective of this thesis was to investigate the role of the ETO-homologues in hematopoiesis and leukemia. First, the finding of physical interactions between ETO homologues suggested a possible cooperation. Second, a ubiquitous expression was observed for MTGR1 and MTG16 in hematopoietic lineages. We also discovered that the expression of ETO was restricted to the erythroid lineage suggesting a role for ETO in erythroid development. Furthermore, we found that MTG16 was downregulated during erythroid and granulocytic differentiation, which also implements a role for MTG16 in the regulation of hematopoietic differentiation. Additionally, cells expressing AML1-ETO showed downregulation of MTG16, which possibly can contribute to the impaired differentiation of these cells. Finally, we studied the transcriptional repression of the ETO-homologues in a reporter gene system. MTG16 was found to be a potent co-repressor. Despite a physical interaction, the co-repressors N-CoR and hSIN3B did not augment MTG16-mediated repression. Collectively, our data suggests that the ETO homologues may have differential roles in the regulation of hematopoietic differentiation.
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| 45. |
- Olsson, Robin, et al.
(author)
-
Analytical modelling and FE simulation of impact response and damage growth in a thin-ply laminate
- 2015
-
In: ICCM International Conferences on Composite Materials. - : International Committee on Composite Materials.
-
Conference paper (peer-reviewed)abstract
- Thin-ply composites offer reduced or suppressed matrix cracking and higher strains to first ply failure. Initial tests indicate a significantly different impact damage than for conventional composites, with less delamination and more fibre fracture. The current paper presents models focused on the observed fibre damage, including an analytical model for the response and damage initiation during impact on thin ply composites as well as a finite element FE model for prediction of damage growth. The limitations and challenges of the analytical model and FE model are discussed and illustrated by comparisons with response histories and fractography for drop weight impact on a thin-ply composite laminate.
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| 46. |
- Olsson, Robin, et al.
(author)
-
Testing and modelling of tension after impact of a thin ply textile composite
- 2016
-
In: ECCM 2016 - Proceeding of the 17th European Conference on Composite Materials. - : European Conference on Composite Materials, ECCM. - 9783000533877
-
Conference paper (peer-reviewed)abstract
- This paper presents an experimental and numerical study of impact response, damage and tension after impact of thin ply HTS45/RTM6 carbon/epoxy laminates, manufactured via resin transfer moulding. A plain weave from carbon fibre spread-tow bands was used in a quasi-isotropic layup. Finite element simulations were performed using layered shell elements accounting for in-plane damage mechanics, with cohesive surfaces between a few layers of shell elements to account for delamination. The damage was found to include a combination of fibre damage and delaminations, in contrast to a previous study on similar cross-ply laminates, where fibre damage dominated. The rate of decrease in tensile strength after impact was similar to prepreg laminates with conventional ply thickness, but the impacted strength was slightly higher due to a higher undamaged strength for thin ply laminates.
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| 47. |
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| 48. |
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| 49. |
- Rehn, Matilda, et al.
(author)
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Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche.
- 2011
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:6, s. 1534-1543
-
Journal article (peer-reviewed)abstract
- Hypoxia is emerging as an important characteristic of the hematopoietic stem cell (HSC) niche, but the molecular mechanisms contributing to quiescence, self-renewal, and survival remain elusive. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis and hematopoiesis. Its expression is commonly regulated by hypoxia-inducible factors (HIF) that are functionally induced in low-oxygen conditions and that activate transcription by binding to hypoxia-response elements (HRE). Vegfa is indispensable for HSC survival, mediated by a cell-intrinsic, autocrine mechanism. We hypothesized that a hypoxic HSC microenvironment is required for maintenance or upregulation of Vegfa expression in HSCs and therefore crucial for HSC survival. We have tested this hypothesis in the mouse model Vegfa(δ/δ), where the HRE in the Vegfa promoter is mutated, preventing HIF binding. Vegfa expression was reduced in highly purified HSCs from Vegfa(δ/δ) mice, showing that HSCs reside in hypoxic areas. Loss of hypoxia-regulated Vegfa expression increases the numbers of phenotypically defined hematopoietic stem and progenitor cells. However, HSC function was clearly impaired when assessed in competitive transplantation assays. Our data provide further evidence that HSCs reside in a hypoxic microenvironment and demonstrate a novel way in which the hypoxic niche affects HSC fate, via the hypoxia-Vegfa axis.
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| 50. |
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