| 1. |
- Howe, LJ, et al.
(författare)
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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:65, s. 581-
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Tidskriftsartikel (refereegranskat)abstract
- Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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| 2. |
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| 3. |
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| 4. |
- Illana, A., et al.
(författare)
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Coulomb excitation of 74,76Zn
- 2023
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Ingår i: Physical Review C. - 2469-9985. ; 108:4
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Tidskriftsartikel (refereegranskat)abstract
- The first experiment using radioactive beams post-accelerated by the HIE-ISOLDE facility has enabled to obtain a precise set of B(E2) transition probabilities in neutron-rich 74,76Zn isotopes. The resulting B(E2; 2+1→0+1) values are consistent with those determined in earlier REX-ISOLDE measurements. While the B(E2; 4+1→2+1) transition probability in 76Zn is also in agreement with earlier Coulomb-excitation results, the value obtained for 74Zn is considerably lower. For the first time, a spectroscopic quadrupole moment of the 2+1 state was measured for an exotic nucleus in this mass region. A detailed comparison is presented with large-scale shell-model and Monte Carlo shell-model calculations.
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| 6. |
- Bekkhus, Tove, et al.
(författare)
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Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Tumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer. The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
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| 7. |
- Brandao, Luiz Eduardo M., et al.
(författare)
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Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial
- 2022
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (similar to 27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.
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| 8. |
- Havukainen, Martti, et al.
(författare)
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A Case Study on Co-designing Digital Games with Older Adults and Children : Game Elements, Assets, and Challenges
- 2020
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Ingår i: The Computer Games Journal. - : Springer. - 2052-773X. ; 9:2, s. 163-188
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Tidskriftsartikel (refereegranskat)abstract
- Digital games have traditionally been targeted at younger generations, although the proportion of older adult players is increasing. However, the design processes of digital games often do not consider the special needs of older adults. Co-design is a potential method to address this, but there is little research on co-designing games with older adults. In our study, we proposed a co-design process model that considers the intergenerational perspective. Using this model, eight older adults (two males and six females aged 47–80) and 22 sixth graders (11 males and 11 females aged 12–13) co-designed a digital game. The content of the game was based on old concepts used by the designers during their childhood. Similarly, game content involving new words and concepts were produced by the sixth graders. We collected data using semi-structured interviews and observations during the co-design process over a period of 24 months and then processed the data using grounded theory. The results indicated that the older adults identified seven game elements as essential to make games fun—appearance and aesthetics, competition, manageability of gameplay, social impact, familiarity, unpredictability, and intergenerational gameplay. Furthermore, we identified six assets that older adults have as game co-designers and five challenges that co-designing games with older adults may entail.
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| 9. |
- Mackenbach, J. P., et al.
(författare)
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Progress against inequalities in mortality : register-based study of 15 European countries between 1990 and 2015
- 2020
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Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 34:12, s. 1131-1142
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic inequalities in mortality are a challenge for public health around the world, but appear to be resistant to policy-making. We aimed to identify European countries which have been more successful than others in narrowing inequalities in mortality, and the factors associated with narrowing inequalities. We collected and harmonised mortality data by educational level in 15 European countries over the last 25 years, and quantified changes in inequalities in mortality using a range of measures capturing different perspectives on inequality (e.g., ‘relative’ and ‘absolute’ inequalities, inequalities in ‘attainment’ and ‘shortfall’). We determined which causes of death contributed to narrowing of inequalities, and conducted country- and period-fixed effects analyses to assess which country-level factors were associated with narrowing of inequalities in mortality. Mortality among the low educated has declined rapidly in all European countries, and a narrowing of absolute, but not relative inequalities was seen in many countries. Best performers were Austria, Italy (Turin) and Switzerland among men, and Spain (Barcelona), England and Wales, and Austria among women. Ischemic heart disease, smoking-related causes (men) and amenable causes often contributed to narrowing inequalities. Trends in income inequality, level of democracy and smoking were associated with widening inequalities, but rising health care expenditure was associated with narrowing inequalities. Trends in inequalities in mortality have not been as unfavourable as often claimed. Our results suggest that health care expansion has counteracted the inequalities widening effect of other influences. © 2019, The Author(s).
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| 10. |
- Martikainen, Maria-Viola, et al.
(författare)
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TUBE project: Transport-derived ultrafines and the brain effects
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- The adverse effects of air pollutants on the respiratory and cardiovascular systems are unquestionable. However, in recent years, indications of effects beyond these organ systems have become more evident. Traffic-related air pollution has been linked with neurological diseases, exacerbated cognitive dysfunction, and Alzheimer’s disease. However, the exact air pollutant compositions and exposure scenarios leading to these adverse health effects are not known. Although several components of air pollution may be at play, recent experimental studies point to a key role of ultrafine particles (UFPs). While the importance of UFPs has been recognized, almost nothing is known about the smallest fraction of UFPs, and only >23 nm emissions are regulated in the EU. Moreover, the role of the semivolatile fraction of the emissions has been neglected. The Transport-Derived Ultrafines and the Brain Effects (TUBE) project will increase knowledge on harmful ultrafine air pollutants, as well as semivolatile compounds related to adverse health effects. By including all the major current combustion and emission control technologies, the TUBE project aims to provide new information on the adverse health effects of current traffic, as well as information for decision makers to develop more effective emission legislation. Most importantly, the TUBE project will include adverse health effects beyond the respiratory system; TUBE will assess how air pollution affects the brain and how air pollution particles might be removed from the brain. The purpose of this report is to describe the TUBE project, its background, and its goals.
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