Kronborghansen2203

We confirmed that the gene(s) from group O is(are) not present in A. thaliana and is(are) also missing in the family Brassicaceae. However, cisZOG or its metabolites are found among Brassicaceae clade, indicating that remaining genes from other groups (UGT73-group D and UGT85-group G) are able, at least in part, to substitute the function of group O lost during evolution. This study is the first detailed evolutionary evaluation of relationships among different plant ZOGs within angiosperms.APOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. Foscenvivint Epigenetic Reader Domain inhibitor The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.Pathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to produce RS, SI and control F1 offspring, respectively. Compared to controls, while paternal RS decreased anxiety-like behavior (ALB) in both female and male offspring, paternal SI increased ALB only in female offspring. Next-generation sequencing and bioinformatics using RS and SI female offspring identified 5 candidate anxiety-transmitting (CAT) genes; each showed a consistent pattern of DNA methylation from F0 spermatozoa through F1 blastocysts to fetal and adult hippocampi. Further analyses validated 4 CAT genes, demonstrated that paternal SI caused ALB differences between male and female offspring through modifying the CAT genes, and indicated a strong correlation between inflammation and ALB pathogenesis and an important function for intronic DNA methylation in regulating ALB-related genes. In conclusion, this study identified important CAT genes and suggested the possibility that stresses on males might alter offspring's ALB by modifying sperm DNA methylation.Cortisol is often measured as a marker for stress. Therefore, a profound validation of the time-lag between the stressor and the increase and peak in cortisol levels is needed. No study measured both the urinary and salivary cortisol time-lag after a psychological stressor. In this study, we used a frequent sampling study design to (1) describe the urinary and salivary cortisol pattern during a control day; and (2) characterize the induced excretion pattern of urinary and salivary cortisol after a psychological stressor in six zoo-housed bonobos. Liquid chromatography-tandem mass spectrometry was used to analyze 71 urine and 162 saliva samples collected on a control and a test day. We found that the time-lag between the stressor and the maximal cortisol concentration was similar in urine and saliva (160 min after the stressor). However, salivary cortisol after the stressor did show a faster and steeper increase than urinary cortisol. We also show inter-individual variation in the baseline and stress levels of cortisol, which should be considered in future cortisol studies. Our research highlights the importance of validation studies to confirm relevant sampling windows for cortisol sampling in order to obtain biologically meaningful results.Parkinsonian motor symptoms are linked to pathologically increased beta-oscillations in the basal ganglia. While pharmacological treatment and deep brain stimulation (DBS) reduce these pathological oscillations concomitantly with improving motor performance, we set out to explore neurofeedback as an endogenous modulatory method. We implemented real-time processing of pathological subthalamic beta oscillations through implanted DBS electrodes to provide deep brain electrical neurofeedback. Patients volitionally controlled ongoing beta-oscillatory activity by visual neurofeedback within minutes of training. During a single one-hour training session, the reduction of beta-oscillatory activity became gradually stronger and we observed improved motor performance. Lastly, endogenous control over deep brain activity was possible even after removing visual neurofeedback, suggesting that neurofeedback-acquired strategies were retained in the short-term. Moreover, we observed motor improvement when the learnt mental strategies were applied 2 days later without neurofeedback. Further training of deep brain neurofeedback might provide therapeutic benefits for Parkinson patients by improving symptom control using strategies optimized through neurofeedback.Streptococcus pneumoniae invades the CNS and triggers a strong cellular response. To date, signaling events that occur in the human brain microvascular endothelial cells (hBMECs), in response to pneumococci or its surface adhesins are not mapped comprehensively. We evaluated the response of hBMECs to the adhesion lipoprotein (a laminin binding protein-Lbp) or live pneumococci. Lbp is a surface adhesin recently identified as a potential ligand, which binds to the hBMECs. Transcriptomic analysis was performed by RNA-seq of three independent biological replicates and validated with qRT-PCR using 11 genes. In total 350 differentially expressed genes (DEGs) were identified after infection with S. pneumoniae, whereas 443 DEGs when challenged with Lbp. Total 231 DEGs were common in both treatments. Integrative functional analysis revealed participation of DEGs in cytokine, chemokine, TNF signaling pathways and phagosome formation. Moreover, Lbp induced cell senescence and breakdown, and remodeling of ECM. This is the first report which maps complete picture of cell signaling events in the hBMECs triggered against S.