| 1. |
- Badam, Tejaswi, et al.
(författare)
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CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases
- 2022
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Ingår i: Epigenetics. - : Taylor & Francis Group. - 1559-2294 .- 1559-2308. ; 17:9, s. 1040-1055
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.
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| 2. |
- Bensberg, Maike, et al.
(författare)
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TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:34
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggres-sive malignancy resulting from overproduction of immature T-cells in the thymus and is typified by widespread alterations in DNA methyl-ation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development of targeted therapies to prevent relapse is key to improv-ing prognosis. Whereas mutations in the DNA demethylating enzyme TET2 are frequent in adult T-cell malignancies, TET2 mutations in T-ALL are rare. Here, we analyzed RNA-sequencing data of 321 primary T-ALLs, 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 is transcriptionally repressed or silenced in 71% and 17% of T-ALL, respec-tively. Furthermore, we show that TET2 silencing is often associated with hypermethylation of the TET2 promoter in primary T-ALL. Impor-tantly, treatment with the DNA demethylating agent, 5-azacytidine (5-aza), was significantly more toxic to TET2-silenced T-ALL cells and resulted in stable re-expression of the TET2 gene. Additionally, 5-aza led to up-regulation of methylated genes and human endogenous ret-roviruses (HERVs), which was further enhanced by the addition of phys-iological levels of vitamin C, a potent enhancer of TET activity. Together, our results clearly identify 5-aza as a potential targeted therapy for TET2-silenced T-ALL.
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| 3. |
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Beyond Borders : Essays on Entrepreneurship, Co-operatives and Education in Sweden and Tanzania
- 2021. - 1
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- The two topics highlighted in this volume, entrepreneurship and co-operatives, and education within these fields, may be regarded as essentially disparate themes. However, looking more closely it is apparent that these have some interesting intersections. The main focus relates to innovation and entrepreneurship among co-operatives, the public sector, and the private sectorThis work is a product of the collaboration between Södertörn University in Stockholm, Sweden, and Moshi Co-operative University in Moshi, Tanzania. In both countries we aim to understand, how enterprises with different ownership forms and other kinds of state and private organizations contribute to economic growth or decline. The volume is an overview of research about entrepreneurship and co-operatives but also of education in these areas. The intention is to contribute to the promotion of research on these topics in both countries and enhance future collaboration between the two Universities.
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| 4. |
- Björnsson, Bergthor, et al.
(författare)
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Digital twins to personalize medicine
- 2020
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
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| 5. |
- David, P., et al.
(författare)
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Gaia Focused Product Release: Asteroid orbital solution : Properties and assessment
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- Context. We report the exploitation of a sample of Solar System observations based on data from the third Gaia Data Release (Gaia DR3) of nearly 157 000 asteroids. It extends the epoch astrometric solution over the time coverage planned for the Gaia DR4, which is not expected before the end of 2025. This data set covers more than one full orbital period for the vast majority of these asteroids. The orbital solutions are derived from the Gaia data alone over a relatively short arc compared to the observation history of many of these asteroids.Aims. The work aims to produce orbital elements for a large set of asteroids based on 66 months of accurate astrometry provided by Gaia and to assess the accuracy of these orbital solutions with a comparison to the best available orbits derived from independent observations. A second validation is performed with accurate occultation timings.Methods. We processed the raw astrometric measurements of Gaia to obtain astrometric positions of moving objects with 1D sub-mas accuracy at the bright end. For each asteroid that we matched to the data, an orbit fitting was attempted in the form of the best fit of the initial conditions at the median epoch. The force model included Newtonian and relativistic accelerations to derive the observation equations, which were solved with a linear least-squares fit.Results. Orbits are provided in the form of state vectors in the International Celestial Reference Frame for 156 764 asteroids, including near-Earth objects, main-belt asteroids, and Trojans. For the asteroids with the best observations, the (formal) relative uncertainty σa/a is better than 10-10. Results are compared to orbits available from the Jet Propulsion Laboratory and MPC. Their orbits are based on much longer data arcs, but from positions of lower quality. The relative differences in semi-major axes have a mean of 5 × 10-10 and a scatter of 5 × 10-9
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| 6. |
- De Ridder, J., et al.
(författare)
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Gaia Data Release 3: Pulsations in main sequence OBAF-type stars
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (M ≥ 1.3 M⊙) of spectral types O, B, A, or F, known as β Cep, slowly pulsating B (SPB), δ Sct, and γ Dor stars. These stars are often multi-periodic and display low amplitudes, making them challenging targets to analyse with sparse time series.Aims. We investigate the extent to which the sparse Gaia DR3 data can be used to detect OBAF-type pulsators and discriminate them from other types of variables. We aim to probe the empirical instability strips and compare them with theoretical predictions. The most populated variability class is that of the δ Sct variables. For these stars, we aim to confirm their empirical period-luminosity (PL) relation, and verify the relation between their oscillation amplitude and rotation.Methods. All datasets used in this analysis are part of the Gaia DR3 data release. The photometric time series were used to perform a Fourier analysis, while the global astrophysical parameters necessary for the empirical instability strips were taken from the Gaia DR3 gspphot tables, and the v sin i data were taken from the Gaia DR3 esphs tables. The δ Sct PL relation was derived using the same photometric parallax method as the one recently used to establish the PL relation for classical Cepheids using Gaia data.Results. We show that for nearby OBAF-type pulsators, the Gaia DR3 data are precise and accurate enough to pinpoint them in the Hertzsprung-Russell (HR) diagram. We find empirical instability strips covering broader regions than theoretically predicted. In particular, our study reveals the presence of fast rotating gravity-mode pulsators outside the strips, as well as the co-existence of rotationally modulated variables inside the strips as reported before in the literature. We derive an extensive period–luminosity relation for δ Sct stars and provide evidence that the relation features different regimes depending on the oscillation period. We demonstrate how stellar rotation attenuates the amplitude of the dominant oscillation mode of δ Sct stars.Conclusions. The Gaia DR3 time-series photometry already allows for the detection of the dominant (non-)radial oscillation mode in about 100 000 intermediate- and high-mass dwarfs across the entire sky. This detection capability will increase as the time series becomes longer, allowing the additional delivery of frequencies and amplitudes of secondary pulsation modes.
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| 7. |
- Drimmel, R., et al.
(författare)
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Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. With the most recent Gaia data release, the number of sources with complete 6D phase space information (position and velocity) has increased to well over 33 million stars, while stellar astrophysical parameters are provided for more than 470 million sources, and more than 11 million variable stars are identified.Aims. Using the astrophysical parameters and variability classifications provided in Gaia DR3, we selected various stellar populations to explore and identify non-axisymmetric features in the disc of the Milky Way in configuration and velocity space.Methods. Using more about 580 000 sources identified as hot OB stars, together with 988 known open clusters younger than 100 Myr, we mapped the spiral structure associated with star formation 4−5 kpc from the Sun. We selected over 2800 Classical Cepheids younger than 200 Myr that show spiral features extending as far as 10 kpc from the Sun in the outer disc. We also identified more than 8.7 million sources on the red giant branch (RGB), of which 5.7 million have line-of-sight velocities. This later sample allows the velocity field of the Milky Way to be mapped as far as 8 kpc from the Sun, including the inner disc.Results. The spiral structure revealed by the young populations is consistent with recent results using Gaia EDR3 astrometry and source lists based on near-infrared photometry, showing the Local (Orion) Arm to be at least 8 kpc long, and an outer arm consistent with what is seen in HI surveys, which seems to be a continuation of the Perseus arm into the third quadrant. The subset of RGB stars with velocities clearly reveals the large-scale kinematic signature of the bar in the inner disc, as well as evidence of streaming motions in the outer disc that might be associated with spiral arms or bar resonances. A local comparison of the velocity field of the OB stars reveals similarities and differences with the RGB sample.Conclusions. This cursory study of Gaia DR3 data shows there is a rich bounty of kinematic information to be explored more deeply, which will undoubtedly lead us to a clearer understanding of the dynamical nature of the non-axisymmetric structures of the Milky Way.
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| 8. |
- Franks, P. W., et al.
(författare)
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Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
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Forskningsöversikt (refereegranskat)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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| 9. |
- Galluccio, L., et al.
(författare)
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Gaia Data Release 3: Reflectance spectra of Solar System small bodies
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Gaia mission of the European Space Agency (ESA) has been routinely observing Solar System objects (SSOs) since the beginning of its operations in August 2014. The Gaia data release three (DR3) includes, for the first time, the mean reflectance spectra of a selected sample of 60 518 SSOs, primarily asteroids, observed between August 5, 2014, and May 28, 2017. Each reflectance spectrum was derived from measurements obtained by means of the Blue and Red photometers (BP/RP), which were binned in 16 discrete wavelength bands. For every spectrum, the DR3 also contains additional information about the data quality for each band.Aims. We describe the processing of the Gaia spectral data of SSOs, explaining both the criteria used to select the subset of asteroid spectra published in Gaia DR3, and the different steps of our internal validation procedures. In order to further assess the quality of Gaia SSO reflectance spectra, we carried out external validation against SSO reflectance spectra obtained from ground-based and space-borne telescopes and available in the literature; we present our validation approach.Methods. For each selected SSO, an epoch reflectance was computed by dividing the calibrated spectrum observed by the BP/RP at each transit on the focal plane by the mean spectrum of a solar analogue. The latter was obtained by averaging the Gaia spectral measurements of a selected sample of stars known to have very similar spectra to that of the Sun. Finally, a mean of the epoch reflectance spectra was calculated in 16 spectral bands for each SSO.Results. Gaia SSO reflectance spectra are in general agreement with those obtained from a ground-based spectroscopic campaign specifically designed to cover the same spectral interval as Gaia and mimic the illumination and observing geometry characterising Gaia SSO observations. In addition, the agreement between Gaia mean reflectance spectra and those available in the literature is good for bright SSOs, regardless of their taxonomic spectral class. We identify an increase in the spectral slope of S-type SSOs with increasing phase angle. Moreover, we show that the spectral slope increases and the depth of the 1 μm absorption band decreases for increasing ages of S-type asteroid families. The latter can be interpreted as proof of progressive ageing of S-type asteroid surfaces due to their exposure to space weathering effects.
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| 10. |
- Gawel, Danuta, et al.
(författare)
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Clinical translation of genomic medicine : Stor potential när genomikdata kan implementeras i klinisk rutin.
- 2021
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Ingår i: Läkartidningen. - 1652-7518. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Recent technical developments and early clinical examples support that precision medicine has potential to provide novel diagnostic and therapeutic solutions for patients with complex diseases, who are not responding to existing therapies. Those solutions will require integration of genomic data with routine clinical, imaging, sensor, biobank and registry data. Moreover, user-friendly tools for informed decision support for both patients and clinicians will be needed. While this will entail huge technical, ethical, societal and regulatory challenges, it may contribute to transforming and improving health care towards becoming predictive, preventive, personalised and participatory (4P-medicine).
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