| 1. |
- Kananen, L, et al.
(författare)
-
Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
- 2023
-
Ingår i: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 45:1, s. 85-103
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
|
|
| 2. |
- Kananen, L, et al.
(författare)
-
Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 6139-
-
Tidskriftsartikel (refereegranskat)abstract
- Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual’s subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.
|
|
| 3. |
- Poorter, Lourens, et al.
(författare)
-
Functional recovery of secondary tropical forests
- 2021
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:49, s. e2003405118-e2003405118
-
Tidskriftsartikel (refereegranskat)abstract
- One-third of all Neotropical forests are secondary forests that regrow naturally after agricultural use through secondary succession. We need to understand better how and why succession varies across environmental gradients and broad geographic scales. Here, we analyze functional recovery using community data on seven plant characteristics (traits) of 1,016 forest plots from 30 chronosequence sites across the Neotropics. By analyzing communities in terms of their traits, we enhance understanding of the mechanisms of succession, assess ecosystem recovery, and use these insights to propose successful forest restoration strategies. Wet and dry forests diverged markedly for several traits that increase growth rate in wet forests but come at the expense of reduced drought tolerance, delay, or avoidance, which is important in seasonally dry forests. Dry and wet forests showed different successional pathways for several traits. In dry forests, species turnover is driven by drought tolerance traits that are important early in succession and in wet forests by shade tolerance traits that are important later in succession. In both forests, deciduous and compound-leaved trees decreased with forest age, probably because microclimatic conditions became less hot and dry. Our results suggest that climatic water availability drives functional recovery by influencing the start and trajectory of succession, resulting in a convergence of community trait values with forest age when vegetation cover builds up. Within plots, the range in functional trait values increased with age. Based on the observed successional trait changes, we indicate the consequences for carbon and nutrient cycling and propose an ecologically sound strategy to improve forest restoration success.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Ravaioli, F, et al.
(författare)
-
DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome
- 2022
-
Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 792165-
-
Tidskriftsartikel (refereegranskat)abstract
- Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome.
|
|
| 7. |
- Jones, Geraint H., et al.
(författare)
-
The Comet Interceptor Mission
- 2024
-
Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
-
Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
|
|
| 8. |
- Moreno-Garcia, D., et al.
(författare)
-
A Resonant Graphene NEMS Vibrometer
- 2022
-
Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 18:28
-
Tidskriftsartikel (refereegranskat)abstract
- Measuring vibrations is essential to ensuring building structural safety and machine stability. Predictive maintenance is a central internet of things (IoT) application within the new industrial revolution, where sustainability and performance increase over time are going to be paramount. To reduce the footprint and cost of vibration sensors while improving their performance, new sensor concepts are needed. Here, double-layer graphene membranes are utilized with a suspended silicon proof demonstrating their operation as resonant vibration sensors that show outstanding performance for a given footprint and proof mass. The unveiled sensing effect is based on resonant transduction and has important implications for experimental studies involving thin nano and micro mechanical resonators that are excited by an external shaker.
|
|
| 9. |
- Obon-Santacana, M, et al.
(författare)
-
Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:17
-
Tidskriftsartikel (refereegranskat)abstract
- The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78–0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66–0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41–0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs.
|
|
