Hair Cortisol and Perceived Stress-Predictors for the Onset of Tics?:A European Longitudinal Study on High-Risk Children

Some retrospective studies suggest that psychosocial stressors trigger the onset of tics. This study examined prospective hypothalamic-pituitary-adrenal (HPA) axis activity and perceived stress prior to tic onset. In the present study, 259 children at high risk for developing tics were assessed for hair cortisol concentration (HCC) and parent-on-child-reported perceived stress four-monthly over a three-year period. We used (i) generalised additive modelling (GAM) to investigate the time effects on HCC (hair samples n = 765) and perceived stress (questionnaires n = 1019) prior to tic onset and (ii) binary logistic regression to predict tic onset in a smaller subsample with at least three consecutive assessments (six to nine months before, two to five months before, and at tic onset). GAM results indicated a non-linear increasing course of HCC in children who developed tics, and a steady HCC course in those without tics, as well as a linear-increasing course of perceived stress in both groups. Logistic regression showed that with a higher HCC in hair samples collected in a range of two to five months before tic onset (which refers to cortisol exposure in a range of four to eight months), the relative likelihood of tic onset rose. Our study suggests increased stress prior to tic onset, as evidenced by higher HCC several months before tic onset. </p

Evolution and development of fruits of Erycina pusilla and other orchid species

Fruits play a crucial role in seed dispersal. They open along dehiscence zones. Fruit dehiscence zone formation has been intensively studied in Arabidopsis thaliana. However, little is known about the mechanisms and genes involved in the formation of fruit dehiscence zones in species outside the Brassicaceae. The dehiscence zone of A. thaliana contains a lignified layer, while dehiscence zone tissues of the emerging orchid model Erycina pusilla include a lipid layer. Here we present an analysis of evolution and development of fruit dehiscence zones in orchids. We performed ancestral state reconstructions across the five orchid subfamilies to study the evolution of selected fruit traits and explored dehiscence zone developmental genes using RNA-seq and qPCR. We found that erect dehiscent fruits with non-lignified dehiscence zones and a short ripening period are ancestral characters in orchids. Lignified dehiscence zones in orchid fruits evolved multiple times from non-lignified zones. Furthermore, we carried out gene expression analysis of tissues from different developmental stages of E. pusilla fruits. We found that fruit dehiscence genes from the MADS-box gene family and other important regulators in E. pusilla differed in their expression pattern from their homologs in A. thaliana. This suggests that the current A. thaliana fruit dehiscence model requires adjustment for orchids. Additionally, we discovered that homologs of A. thaliana genes involved in the development of carpel, gynoecium and ovules, and genes involved in lipid biosynthesis were expressed in the fruit valves of E. pusilla, implying that these genes may play a novel role in formation of dehiscence zone tissues in orchids. Future functional analysis of developmental regulators, lipid identification and quantification can shed more light on lipid-layer based dehiscence of orchid fruits

Hair cortisol-a stress marker in children and adolescents with chronic tic disorders? A large European cross-sectional study

Background: There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods: Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3-16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3-10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results: There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion: A link between HCC and TDs is not supported by the present results

Hair cortisol-a stress marker in children and adolescents with chronic tic disorders? A large European cross-sectional study

Background There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion A link between HCC and TDs is not supported by the present result

Dynamic genome evolution in a model fern

The large size and complexity of most fern genomes have hampered efforts to elucidate fundamental aspects of fern biology and land plant evolution through genome-enabled research. Here we present a chromosomal genome assembly and associated methylome, transcriptome and metabolome analyses for the model fern species Ceratopteris richardii. The assembly reveals a history of remarkably dynamic genome evolution including rapid changes in genome content and structure following the most recent whole-genome duplication approximately 60 million years ago. These changes include massive gene loss, rampant tandem duplications and multiple horizontal gene transfers from bacteria, contributing to the diversification of defence-related gene families. The insertion of transposable elements into introns has led to the large size of the Ceratopteris genome and to exceptionally long genes relative to other plants. Gene family analyses indicate that genes directing seed development were co-opted from those controlling the development of fern sporangia, providing insights into seed plant evolution. Our findings and annotated genome assembly extend the utility of Ceratopteris as a model for investigating and teaching plant biology

The Modulating Role of Stress in the Onset and Course of Tourette’s Syndrome: A Review

Accumulating data indicate a common occurrence of tic exacerbations and periods of psychosocial stress. Patients with Tourette’s syndrome (TS) also exhibit aberrant markers of hypothalamic-pituitary-adrenal (HPA) axis activation. Based on these findings, a functional relationship between stress and tic disorders has been suggested, but the underlying mechanism of how stress may affect tic pathology remains to be elucidated. We suggest that dopaminergic and noradrenergic neurotransmission as well as immunology play a crucial role in mediating this relationship. Two possibilities of causal direction might be assumed: (a) psychosocial stress might lead to an exacerbation of tics via activation of HPA axis and subsequent changes in neurotransmission or immunology and (b) TS-related abnormalities in neurotransmission or immunology result in a higher vulnerability of affecte

Hair cortisol-a stress marker in children and adolescents with chronic tic disorders? A large European cross-sectional study.

There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3-16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3-10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. A link between HCC and TDs is not supported by the present results

Evolution and development of fruits of Erycina pusilla and other orchid species.

Fruits play a crucial role in seed dispersal. They open along dehiscence zones. Fruit dehiscence zone formation has been intensively studied in Arabidopsis thaliana. However, little is known about the mechanisms and genes involved in the formation of fruit dehiscence zones in species outside the Brassicaceae. The dehiscence zone of A. thaliana contains a lignified layer, while dehiscence zone tissues of the emerging orchid model Erycina pusilla include a lipid layer. Here we present an analysis of evolution and development of fruit dehiscence zones in orchids. We performed ancestral state reconstructions across the five orchid subfamilies to study the evolution of selected fruit traits and explored dehiscence zone developmental genes using RNA-seq and qPCR. We found that erect dehiscent fruits with non-lignified dehiscence zones and a short ripening period are ancestral characters in orchids. Lignified dehiscence zones in orchid fruits evolved multiple times from non-lignified zones. Furthermore, we carried out gene expression analysis of tissues from different developmental stages of E. pusilla fruits. We found that fruit dehiscence genes from the MADS-box gene family and other important regulators in E. pusilla differed in their expression pattern from their homologs in A. thaliana. This suggests that the current A. thaliana fruit dehiscence model requires adjustment for orchids. Additionally, we discovered that homologs of A. thaliana genes involved in the development of carpel, gynoecium and ovules, and genes involved in lipid biosynthesis were expressed in the fruit valves of E. pusilla, implying that these genes may play a novel role in formation of dehiscence zone tissues in orchids. Future functional analysis of developmental regulators, lipid identification and quantification can shed more light on lipid-layer based dehiscence of orchid fruits

Good Manufacturing Practice-Compliant Production and Lot-Release of Ex Vivo Expanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders

In recent years, the exploration of regulatory T cell (Treg)-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer. Here, we present a protocol for the GMP-compliant production, lot-release and validation of ex vivo expanded Tregs for treatment of patients with autoimmune and inflammatory disorders. In the presented production protocol, large numbers of Treg, previously enriched from a leukapheresis product by using the CliniMACS® system, are ex vivo expanded in the presence of anti-CD3/anti-CD28 expander beads, exogenous IL-2 and rapamycin during 21 days. The expanded Treg drug product passed predefined lot-release criteria. These criteria include (i) sterility testing, (ii) assessment of Treg phenotype, (iii) assessment of non-Treg cellular impurities, (iv) confirmation of successful anti-CD3/anti-CD28 expander bead removal after expansion, and (v) confirmation of the biological function of the Treg product. Furthermore, the Treg drug product was shown to retain its stability and suppressive function for at least 1 year after freezing and thawing. Also, dilution of the Treg drug product in 0.9% physiological saline did not affect Treg phenotype and Treg function for up to 90 min. These data indicate that these cells are ready to use in a clinical setting in which a cell infusion time of up to 90 min can be expected. The presented production process has recently undergone on site GMP-conform evaluation and received GMP certification from the Bavarian authorities in Germany. This protocol can now be used for Treg-based therapy of various inflammatory and autoimmune disorders