| 1. |
- Kuschmierz, Paul, et al.
(författare)
-
European first-year university students accept evolution but lack substantial knowledge about it : A standardized European cross-country assessment
- 2021
-
Ingår i: Evolution. - : BioMed Central (BMC). - 1936-6426 .- 1936-6434. ; 14:1, s. 1-22
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Investigations of evolution knowledge and acceptance and their relation are central to evolution education research. Ambiguous results in this field of study demonstrate a variety of measuring issues, for instance differently theorized constructs, or a lack of standardized methods, especially for cross-country comparisons. In particular, meaningful comparisons across European countries, with their varying cultural backgrounds and education systems, are rare, often include only few countries, and lack standardization. To address these deficits, we conducted a standardized European survey, on 9200 first-year university students in 26 European countries utilizing a validated, comprehensive questionnaire, the “Evolution Education Questionnaire”, to assess evolution acceptance and knowledge, as well as influencing factors on evolution acceptance. Results: We found that, despite European countries’ different cultural backgrounds and education systems, European first-year university students generally accept evolution. At the same time, they lack substantial knowledge about it, even if they are enrolled in a biology-related study program. Additionally, we developed a multilevel-model that determines religious faith as the main influencing factor in accepting evolution. According to our model, knowledge about evolution and interest in biological topics also increase acceptance of evolution, but to a much lesser extent than religious faith. The effect of age and sex, as well as the country’s affiliation, students’ denomination, and whether or not a student is enrolled in a biology-related university program, is negligible. Conclusions: Our findings indicate that, despite all their differences, most of the European education systems for upper secondary education lead to acceptance of evolution at least in university students. It appears that, at least in this sample, the differences in knowledge between countries reflect neither the extent to which school curricula cover evolutionary biology nor the percentage of biology-related students in the country samples. Future studies should investigate the role of different European school curricula, identify particularly problematic or underrepresented evolutionary concepts in biology education, and analyze the role of religious faith when teaching evolution.
|
|
| 2. |
|
|
| 3. |
- Argyriou, A, et al.
(författare)
-
Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4046-
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4+ T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4+ T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (TPH) states and a cytotoxic CD4+ T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13high TPH CD4+ T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, TPH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13high TPH CD4+ T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two TPH clusters and effector CD4+ T cells. Our study provides comprehensive immunoprofiling of the synovial CD4+ T cell subsets in ACPA+ and ACPA- RA.
|
|
| 4. |
- Argyriou, A, et al.
(författare)
-
SINGLE CELL SEQUENCING REVEALS CLONALLY EXPANDED CYTOTOXIC CD4+T CELLS IN THE JOINTS OF ACPA plus RA PATIENTS
- 2021
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 38-39
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- CD4+ T cells with cytotoxic functions (CD4+ CTL) have gained attention in recent years. Accumulating evidence supports their importance in defense against human viral infections such as CMV1, EBV2, dengue3, HIV4, 5 and SARS-CoV-26. Moreover, expansion of so called CD28null cytotoxic CD4+ T cells have been reported in the blood of patients with rheumatic diseases such as rheumatoid arthritis (RA)7, myositis8 and vasculitis9 as well as in cardiovascular diseases10.Objectives:Here, we aimed to investigate the presence and clonal expansion of CD4+ CTL in the peripheral blood (PB) and synovial fluid (SF) of RA patients using single cell technologies.Methods:We assessed the expression of cytotoxic effector molecules and transcription factors in CD4+ T cells in synovial fluid (n=21) and paired peripheral blood (n=16) from ACPA- and APCA+ RA patients by multi-parameter flow cytometry. We performed single cell sequencing, in combination with 5´ TCRab sequencing, on purified CD4+ T cells from the peripheral blood (PB) and synovial fluid (SF) of ACPA+ RA patients (n=7).Results:Flow cytometry experiments show that Granzyme-B+ Perforin-1+ CD4+ CTL are significantly increased in the SF of ACPA+ RA patients as compared to ACPA- RA patients (p=0.0072). The presence of CD4+ CTL could be confirmed by single cell sequencing in SF of each ACPA+ RA patient tested (n=7). Moreover, we found that the adhesion G-protein coupled receptor GPR56 is selectively expressed on the recently described peripheral helper (TPH) T-cell subset11 and associates with the expression of tissue resident memory markers LAG-3, CXCR6 and CD69. In blood, we confirmed a previous report12 showing that GPR56 delineates cytotoxic CD4+ T cells. Finally, expanded TCR clones expressing cytotoxic effector molecules were identified in synovial fluid of ACPA+ RA patients and, for some patients, in their corresponding peripheral blood.Conclusion:We identified GPR56 as a marker of TPH cells in SF of ACPA+ RA patients that associates with tissue residency receptors. The combination of single cell sequencing and multi-parameter flow cytometry highlights the importance of CD4+ CTL in ACPA+ RA and suggests a potential therapeutic target (Figure 1).References:[1]Casazza J. P. et al., J Exp Med2006,203 (13), 2865-77.[2]Landais E. et al., Blood2004,103 (4), 1408-16.[3]Kurane I. et al. J Exp Med1989,170 (3), 763-75.[4]Appay V. et al. J Immunol2002,168 (11), 5954-8.[5]Juno J. A. et al. Front Immunol2017,8, 19.[6]Meckiff B. J. et al. Cell2020,183 (5), 1340-1353 e16.[7]Schmidt D. et al. J Clin Invest1996,97 (9), 2027-37.[8]Fasth A. E. et al. J Immunol2009,183 (7), 4792-9.[9]Moosig F. et al. Clin Exp Immunol1998,114 (1), 113-8.[10]Sato K. et al. J Exp Med2006,203 (1), 239-50.[11]Rao D. A., et al. Nature2017,542 (7639), 110-114.[12]Peng Y. M. et al. J Leukoc Biol2011,90 (4), 735-40.Acknowledgements:We thank the patients who donated samples and the medical staff at the Rheumatology Clinic of Karolinska University Hospital. Julia Boström, Gloria Rostvall, and Susana Hernandez Machado are acknowledged for organizing the sampling, storage, and administration of biomaterial. This study is supported by grants from Dr. Margaretha Nilssons, the Nanna Svartz, the Ulla and Gustaf af Ugglas foundations and the Swedish association against rheumatism.Disclosure of Interests:Alexandra Argyriou: None declared, Marc H Wadsworth II Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Adrian Lendvai: None declared, Stephen Christensen Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Aase Hensvold: None declared, Christina Gerstner: None declared, Kellie Kravarik Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Aaron Winkler Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Vivianne Malmström: None declared, Karine Chemin: None declared
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Sečenji, M, et al.
(författare)
-
Differences in root functions during long-term drought adaptation : comparison of active gene sets of two wheat genotypes
- 2010
-
Ingår i: Plant Biology. - : Wiley-Blackwell. - 1435-8603 .- 1438-8677. ; 12:6, s. 871-882
-
Tidskriftsartikel (refereegranskat)abstract
- In an attempt to shed light on the role of root systems in differential responses of wheat genotypes to long-term water limitation, transcriptional differences between two wheat genotypes (Triticum aestivum L., cv. Plainsman V and landrace Kobomugi) were identified during adaptation to moderate water stress at the tillering stage. Differences in organ sizes, water-use efficiency and seed production were detected in plants grown in soil, and root functions were characterised by expression profiling. The molecular genetic background of the behaviour of the two genotypes during this stress was revealed using a cDNA macroarray for transcript profiling of the roots. During a 4-week period of moderate water deficit, a set of up-regulated genes displaying transiently increased expression was identified in young plantlets, mostly in the second week in the roots of Kobomugi, while transcript levels remained constantly high in roots of Plainsman V. These genes encode proteins with various functions, such as transport, protein metabolism, osmoprotectant biosynthesis, cell wall biogenesis and detoxification, and also regulatory proteins. Oxidoreductases, peroxidases and cell wall-related genes were induced significantly only in Plainsman V, while induction of stress- and defence-related genes was more pronounced in Kobomugi. Real-time qPCR analysis of selected members of the glutathione S-transferase gene family revealed differences in regulation of family members in the two genotypes and confirmed the macroarray results. The TaGSTZ gene was stress-activated only in the roots of Kobomugi.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Bausch, Birke, et al.
(författare)
-
Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
-
Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
|
|
