Biology subjects

Almqvist, C.

Publications and source records attributed to Almqvist, C..

6 recordsLinked to original sources

bioRxiv2023

A conserved graft formation process in Picea abies and Arabidopsis thaliana identifies the PAT gene family as central regulators of wound healing

The widespread use of plant grafting has enabled eudicots and gymnosperms to join with closely related species and grow as one. Gymnosperms have dominated forests for over 200 million years and despite their economic and ecological relevance, we know little about how they graft. Here, we developed a micrografting method in conifers using young tissues that allowed efficient grafting between closely related species and distantly related genera. Conifer graft junctions rapidly connected vasculature and differentially expressed thousands of genes including auxin and cell wall-related genes. By comparing these genes to those induced during Arabidopsis thaliana graft formation, we found a common activation of cambium, cell division, phloem and xylem-related genes. A gene regulatory network analysis in Picea abies (Norway spruce) predicted that PHYTOCHROME A SIGNAL TRANSDUCTION 1 (PAT1) acted as a core regulator of graft healing. This gene was strongly upregulation during both P. abies and Arabidopsis grafting, and Arabidopsis mutants lacking PAT-genes failed to attach tissues or successfully graft. Complementing Arabidopsis PAT mutants with the P. abies PAT1 homolog rescued tissue attachment and enhance callus formation. Together, our data demonstrate an ability for young tissues to facilitate grafting with distantly related species and identifies the PAT gene family as conserved regulators of graft healing and tissue regeneration.

plant biology↗

bioRxiv2022

Biological age is increased by stress and restored upon recovery

Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. By applying advanced epigenetic aging clocks, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment of animals. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. Elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

systems biology↗

bioRxiv2019

Comprehensive longitudinal study of epigenetic mutations in aging

BackgroundThe role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.\n\nResultsWe verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.\n\nConclusionsHere we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.

genetics↗

bioRxiv2019

Relation of in-utero exposure to antiepileptic drugs to pregnancy duration and size at birth

BackgroundThe associations of individual antiepileptic drugs (AEDs) with pregnancy duration and size at birth, and potential dose relations, are not well characterized.\n\nMethodsThis cohort study used nationwide Swedish register data (1996-2013). Adjusting for smoking, epilepsy and other AED indications, we used linear and quantile regression to explore associations with pregnancy duration, and birth weight, length, and head circumference (the last three operationalized as z-scores). We used logistic regression for preterm delivery, small for gestational age, and microcephaly. Lamotrigine was the reference drug.\n\nResults6,720 infants were exposed to AEDs in utero; AED exposure increased over the study period. Relative to lamotrigine-exposed infants, carbamazepine-exposed infants were born, on average, 1.3 days earlier (mean [95% confidence interval]: -1.3 [-2.3 to -0.3]); were 0.1 standard deviations (SDs) lighter (-0.1 [-0.2 to 0.0]); and had a head circumference that was 0.2 SDs smaller (-0.2 [-0.3 to -0.1]). Pregabalin-exposed infants were born, on average, 1.1 days earlier (1.1 [-3.0 to 0.8]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had the same head circumference. Levetiracetam-exposed infants were born, on average, 0.5 days earlier (-0.5 [-2.6 to 1.6]); were 0. 1 SDs lighter (-0.1 [-0.3 to 0.0]); and were 0.1 SDs smaller (-0.1 [-0.3 to 0.1]) in head circumference. Valproic acid-exposed infants had, on average, the same duration of gestation and birth weight z-score, but were 0.2 SDs smaller (-0.2 [-0.2 to -0.1]) in head circumference. More negative associations at the left tail of pregnancy duration and birth weight z-score, effect-measure modification, and dose-response relations were noted for some of the associations. Observed associations were generally of smaller magnitude than that of smoking, assessed as a potential confounder in the same models.\n\nConclusionsIn comparison with lamotrigine, valproic acid and carbamazepine had a more negative association with head circumference than other study AEDs.

epidemiology↗

bioRxiv2019

Asthma and affective traits in adults: a genetically informative study

Depression, anxiety and high neuroticism (affective traits) are often comorbid with asthma. A causal direction between the affective traits and asthma is difficult to determine, however, it may be that there is a common underlying pathway attributable to shared genetic factors. Our aim was to determine whether a common genetic susceptibility exists for asthma and each of the affective traits. An adult twin cohort from the Swedish Twin Register underwent questionnaire-based health assessments (n=23 693) and genotyping (n=15 908). Firstly, questionnaire-based associations between asthma and affective traits were explored. This was followed by genetic analyses: a) polygenic risk scores (PRS) for affective traits were used as predictors of asthma, and b) linkage-disequilibrium score regression based on genome-wide association results from UK Biobank was used to quantify genetic correlations. Analyses found that the questionnaire-based associations between asthma and each affective trait were associated (OR 1.7, 95%CI 1.5-1.9 major depression, OR 1.5, 95%CI 1.3-1.6 anxiety, and OR 1.6, 95% 1.4-1.8 high neuroticism). Genetic susceptibility for neuroticism explained the variance in asthma with a dose response effect; that is, those in the highest neuroticism PRS quartile were more likely to have asthma than those in the lowest quartile (OR 1.4, 95%CI 1.2-1.6). Genetic correlations were found between depression and asthma (rg= 0.17), but not for anxiety or neuroticism score. We conclude that the observed comorbidity between asthma and the affective traits may in part be due to shared genetic influences between asthma and depression and neuroticism, but not anxiety.

genetics↗

bioRxiv2017

Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins

Age-related changes in DNA methylation have been observed in many cross-sectional studies, but longitudinal evidence is still very limited. Here, we aimed to characterize longitudinal age-related methylation patterns (Illumina HumanMethylation450 array) using 1011 blood samples collected from 385 old Swedish twins (mean age of 69 at baseline) up to five times over 20 years. We identified 1316 age-associated methylation sites (p<1.3x10-7) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in PIVUS (p<3.9x10-5) and 594 were replicated in LBC (p<5.1x10-5). Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other unannotated transcription factor binding sites. We further investigated genetic influences on methylation (methylation quantitative trait loci) and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased over time, where monozygotic twins had smaller intra-pair differences than dizygotic twins. We show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. Moreover, the changes are under genetic influence, although this effect is independent of age. In addition, inter-individual methylation variations increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.

genetics↗