| 1. |
- Middeldorp, Christel M., et al.
(författare)
-
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
|
|
| 2. |
- Edvardsson, David, et al.
(författare)
-
Advancing Long-Term Care Science Through Using Common Data Elements : Candidate Measures for Care Outcomes of Personhood, Well-Being, and Quality of Life
- 2019
-
Ingår i: Gerontology and geriatric medicine. - : Sage Publications. - 2333-7214. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- To support the development of internationally comparable common data elements (CDEs) that can be used to measure essential aspects of long-term care (LTC) across low-, middle-, and high-income countries, a group of researchers in medicine, nursing, behavioral, and social sciences from 21 different countries have joined forces and launched the Worldwide Elements to Harmonize Research in LTC Living Environments (WE-THRIVE) initiative. This initiative aims to develop a common data infrastructure for international use across the domains of organizational context, workforce and staffing, person-centered care, and care outcomes, as these are critical to LTC quality, experiences, and outcomes. This article reports measurement recommendations for the care outcomes domain, focusing on previously prioritized care outcomes concepts of well-being, quality of life (QoL), and personhood for residents in LTC. Through literature review and expert ranking, we recommend nine measures of well-being, QoL, and personhood, as a basis for developing CDEs for long-term care outcomes across countries. Data in LTC have often included deficit-oriented measures; while important, reductions do not necessarily mean that residents are concurrently experiencing well-being. Enhancing measurement efforts with the inclusion of these positive LTC outcomes across countries would facilitate international LTC research and align with global shifts toward healthy aging and person-centered LTC models.
|
|
| 3. |
|
|
| 4. |
- Lagerholm, Vendela K., et al.
(författare)
-
Range shifts or extinction? Ancient DNA and distribution modelling reveal past and future responses to climate warming in cold-adapted birds
- 2017
-
Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:4, s. 1425-1435
-
Tidskriftsartikel (refereegranskat)abstract
- Global warming is predicted to cause substantial habitat rearrangements, with the most severe effects expected to occur in high-latitude biomes. However, one major uncertainty is whether species will be able to shift their ranges to keep pace with climate-driven environmental changes. Many recent studies on mammals have shown that past range contractions have been associated with local extinctions rather than survival by habitat tracking. Here, we have used an interdisciplinary approach that combines ancient DNA techniques, coalescent simulations and species distribution modelling, to investigate how two common cold-adapted bird species, willow and rock ptarmigan (Lagopus lagopus and Lagopus muta), respond to long-term climate warming. Contrary to previous findings in mammals, we demonstrate a genetic continuity in Europe over the last 20 millennia. Results from back-casted species distribution models suggest that this continuity may have been facilitated by uninterrupted habitat availability and potentially also the greater dispersal ability of birds. However, our predictions show that in the near future, some isolated regions will have little suitable habitat left, implying a future decrease in local populations at a scale unprecedented since the last glacial maximum.
|
|
| 5. |
- Nik-Zainal, Serena, et al.
(författare)
-
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
-
Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
|
|
| 6. |
- Palor, Machaela, et al.
(författare)
-
Cholesterol sensing by CD81 is important for hepatitis C virus entry
- 2020
-
Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 295:50, s. 16931-16948
-
Tidskriftsartikel (refereegranskat)abstract
- CD81 plays a role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus. Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81-cholesterol association, but had disparate effects on HCV, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified an allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol unbound) or closed (cholesterol bound) conformation. The open mutant of CD81 exhibited reduced receptor activity whereas the closed mutant was enhanced. These data are consistent with cholesterol switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81-partner networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in health and disease.
|
|
| 7. |
- Shepherd, Rosalie H., et al.
(författare)
-
Measurement of gas-phase OH radical oxidation and film thickness of organic films at the air-water interface using material extracted from urban, remote and wood smoke aerosol
- 2022
-
Ingår i: Environmental Science. - : Royal Society of Chemistry (RSC). - 2634-3606. ; 2:4, s. 574-590
-
Tidskriftsartikel (refereegranskat)abstract
- The presence of an organic film on a cloud droplet or aqueous aerosol particle has the potential to alter the chemical, optical and physical properties of the droplet or particle. In the study presented, water insoluble organic materials extracted from urban, remote (Antarctica) and wood burning atmospheric aerosol were found to have stable, compressible, films at the air-water interface that were typically similar to 6-18 angstrom thick. These films are reactive towards gas-phase OH radicals and decay exponentially, with bimolecular rate constants for reaction with gas-phase OH radicals of typically 0.08-1.5 x 10(-10) cm(3) molecule(-1) s(-1). These bimolecular rate constants equate to initial OH radical uptake coefficients estimated to be similar to 0.6-1 except woodsmoke (similar to 0.05). The film thickness and the neutron scattering length density of the extracted atmosphere aerosol material (from urban, remote and wood burning) were measured by neutron reflection as they were exposed to OH radicals. For the first time neutron reflection has been demonstrated as an excellent technique for studying the thin films formed at air-water interfaces from materials extracted from atmospheric aerosol samples. Additionally, the kinetics of gas-phase OH radicals with a proxy compound, the lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) was studied displaying significantly different behaviour, thus demonstrating it is not a good proxy for atmospheric materials that may form films at the air-water interface. The atmospheric lifetimes, with respect to OH radical oxidation, of the insoluble organic materials extracted from atmospheric aerosol at the air-water interface were a few hours. Relative to a possible physical atmospheric lifetime of 4 days, the oxidation of these films is important and needs inclusion in atmospheric models. The optical properties of these films were previously reported [Shepherd et al., Atmos. Chem. Phys., 2018, 18, 5235-5252] and there is a significant change in top of the atmosphere albedo for these thin films on core-shell atmospheric aerosol using the film thickness data and confirmation of stable film formation at the air-water interface presented here.
|
|
