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Sulfur is present in plants in a large range of essential primary metabolites, as well as in numerous natural products. Many of these secondary metabolites contain sulfur in the oxidized form of organic sulfate. However, except of glucosinolates, very little is known about other classes of such sulfated metabolites, mainly because of lack of specific and quantitative analytical methods. We developed an LC-MS method to analyze sulfated flavonoids, a group of sulfated secondary metabolites prominent, e.g., in plants of the genus . The method uses a linear gradient of methanol/formic acid in water on a Restek Raptor C Core-Shell column for separation of the compounds. The sulfated flavonoids are detected by mass spectrometry (MS) in a negative mode, using a neutral loss of 80 Da after a collision induced dissociation. With this method we were also able to quantify the sulfated flavonoids. We could detect all (mono)sulfated flavonoids described before in plus a number of new ones, such as isorhamnetin-sulfate-glycoside. In addition, we showed that sulfated flavonoids represent a substantial sulfur pool in , larger than the thiols glutathione and cysteine. The individual species possess different sulfated flavonoids, but there is no correlation between the qualitative pattern and type of photosynthesis. Similar to other sulfur-containing secondary compounds, the concentration of sulfated flavonoids in leaves is reduced by sulfur starvation. The new LC-MS method will enable qualitative and quantitative detection of these secondary metabolites in plants as a pre-requisite to addressing their functions.

Although inflammatory bowel disease (IBD) affects patients’ psychological well-being, previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life. Therefore, we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management skills, delivered in an interactive manner, and evaluated it in a large, cluster-randomized trial. We assigned 540 rehabilitation inpatients suffering from IBD (mean age 43 years, 66% female) to either the new intervention or a control group comprising the same overall intensity and the same medical information, but only general psychosocial information. The primary outcome was patient-reported IBD-related concerns. Secondary outcomes included disease knowledge, coping, self-management skills, fear of progression, anxiety, depression and quality of life. Assessments took place at baseline, end of rehabilitation and after 3 and 12 months. The psychoeducational self-management program did not prove superior to the control group regarding primary and secondary outcomes. However, positive changes over time occurred in both groups regarding most outcomes. The superior effectiveness of the newly developed psychoeducational program could not be demonstrated. Since the intervention and control groups may have been too similar, this trial may have been too conservative to produce between-group effects.

Abstract The objective was to evaluate the effectiveness of a self-management patient education programme for fibromyalgia syndrome (FMS) as compared with usual care education in inpatient rehabilitation. In a multicentre cluster-randomized controlled trial, 583 inpatients in 3 rehabilitation centres received an advanced self-management patient education programme or usual care education. Patients completed questionnaires at admission, discharge and after 6 and 12 months. Primary outcomes were disease- and treatment-specific knowledge at discharge, and self-management-competencies after 6 months. Secondary outcomes included satisfaction, attitudes, coping competencies, psychological distress and health impairment. We found a medium-sized effect on disease- and treatment-specific knowledge at discharge (P < 0.05, Cohen’s d = 0.45, 95% CI = 0.27–0.63), and small effects for subjective knowledge, pain-related control, self-monitoring and insight, communication about disease, action planning for physical activity and treatment satisfaction (all P < 0.05). Only the effect on knowledge persisted for 6 and 12 months. This advanced education programme seemed to be more effective in the short term than usual education. However, intermediate- and long-term effects did not emerge. While superior long-term effects on knowledge as well as short-term effects on self-management skills may suggest implementation, additional long-term effects on other patient-relevant outcomes would be desirable. Trial registration: German Clinical Trials Register, DRKS00008782, Registered 8 July 2015.

Sulfur plays a vital role in the primary and secondary metabolism of plants, and carries an important function in a large number of different compounds. Despite this importance, compared to other mineral nutrients, relatively little is known about sulfur sensing and signalling, as well as about the mechanisms controlling sulfur metabolism and homeostasis. Sulfur contents in plants vary largely not only among different species, but also among accessions of the same species. We previously used associative transcriptomics to identify several genes potentially controlling variation in sulfate content in the leaves of Brassica napus, including an OASC gene for mitochondrial O-acetylserine thiollyase (OAS-TL), an enzyme involved in cysteine synthesis. Here, we show that loss of OASC in Arabidopsis thaliana lowers not only sulfate, but also glutathione levels in the leaves. The reduced accumulation is caused by lower sulfate uptake and translocation to the shoots; however, the flux through the pathway is not affected. In addition, we identified a single nucleotide polymorphism in the OASC gene among A. thaliana accessions that is linked to variation in sulfate content. Both genetic and transgenic complementation confirmed that the exchange of arginine at position 81 for lysine in numerous accessions resulted in a less active OASC and a lower sulfate content in the leaves. The mitochondrial isoform of OAS-TL is, thus, after the ATPS1 isoform of sulfurylase and the APR2 form of APS reductase 2, the next metabolic enzyme with a role in regulation of sulfate content in Arabidopsis.

The evolution of C₄ photosynthesis led to an increase in carbon assimilation rates and plant growth compared to C₃ photosynthetic plants. This enhanced plant growth, in turn, affects the requirement for soil-derived mineral nutrients. However, mineral plant nutrition has scarcely been considered in connection with C₄ photosynthesis. Sulfur is crucial for plant growth and development, and preliminary studies in the genus Flaveria suggested metabolic differences in sulfate assimilation along the C₄ evolutionary trajectory. Here, we show that in controlled conditions, foliar accumulation of the reduced sulfur compounds Cys and glutathione (GSH) increased with progressing establishment of the C₄ photosynthetic cycle in different Flaveria species. An enhanced demand for reduced sulfur in C₄ Flaveria species is reflected in high rates of [³⁵S]sulfate incorporation into GSH upon sulfate deprivation and increased GSH turnover as a reaction to the inhibition of GSH synthesis. Expression analyses indicate that the 𝛾-glutamyl cycle is crucial for the recycling of GSH in C₄ species. Sulfate reduction and GSH synthesis seems to be preferentially localized in the roots of C4 species, which might be linked to its colocalization with the phosphorylated pathway of Ser biosynthesis. Interspecies grafting experiments of F. robusta (C₃) and F. bidentis (C₄) revealed that the root system primarily controls sulfate acquisition, GSH synthesis, and sulfate and metabolite allocation in C₃ and C₄ plants. This study thus shows that evolution of C₄ photosynthesis resulted in a wide range of adaptations of sulfur metabolism and points out the need for broader studies on importance of mineral nutrition for C₄ plants.

The evolution of C photosynthesis led to an increase in carbon assimilation rates and plant growth compared to C photosynthetic plants. This enhanced plant growth, in turn, affects the requirement for soil-derived mineral nutrients. However, mineral plant nutrition has scarcely been considered in connection with C photosynthesis. Sulfur is crucial for plant growth and development, and preliminary studies in the genus suggested metabolic differences in sulfate assimilation along the C evolutionary trajectory. Here, we show that in controlled conditions, foliar accumulation of the reduced sulfur compounds Cys and glutathione (GSH) increased with progressing establishment of the C photosynthetic cycle in different species. An enhanced demand for reduced sulfur in C species is reflected in high rates of [ S]sulfate incorporation into GSH upon sulfate deprivation and increased GSH turnover as a reaction to the inhibition of GSH synthesis. Expression analyses indicate that the γ-glutamyl cycle is crucial for the recycling of GSH in C species. Sulfate reduction and GSH synthesis seems to be preferentially localized in the roots of C species, which might be linked to its colocalization with the phosphorylated pathway of Ser biosynthesis. Interspecies grafting experiments of (C ) and (C ) revealed that the root system primarily controls sulfate acquisition, GSH synthesis, and sulfate and metabolite allocation in C and C plants. This study thus shows that evolution of C photosynthesis resulted in a wide range of adaptations of sulfur metabolism and points out the need for broader studies on importance of mineral nutrition for C plants.

Sulfur plays a vital role in the primary and secondary metabolism of plants, and carries an important function in a large number of different compounds. Despite this importance, compared to other mineral nutrients, relatively little is known about sulfur sensing and signalling, as well as about the mechanisms controlling sulfur metabolism and homeostasis. Sulfur contents in plants vary largely not only among different species, but also among accessions of the same species. We previously used associative transcriptomics to identify several genes potentially controlling variation in sulfate content in the leaves of Brassica napus, including an OASC gene for mitochondrial O-acetylserine thiollyase (OAS-TL), an enzyme involved in cysteine synthesis. Here, we show that loss of OASC in Arabidopsis thaliana lowers not only sulfate, but also glutathione levels in the leaves. The reduced accumulation is caused by lower sulfate uptake and translocation to the shoots; however, the flux through the pathway is not affected. In addition, we identified a single nucleotide polymorphism in the OASC gene among A. thaliana accessions that is linked to variation in sulfate content. Both genetic and transgenic complementation confirmed that the exchange of arginine at position 81 for lysine in numerous accessions resulted in a less active OASC and a lower sulfate content in the leaves. The mitochondrial isoform of OAS-TL is, thus, after the ATPS1 isoform of sulfurylase and the APR2 form of APS reductase 2, the next metabolic enzyme with a role in regulation of sulfate content in Arabidopsis.

Background Fibromyalgia syndrome (FMS) is a complex chronic condition that makes high demands on patients’ self-management skills. Thus, patient education is considered an important component of multimodal therapy, although evidence regarding its effectiveness is scarce. The main objective of this study is to assess the effectiveness of an advanced self-management patient education program for patients with FMS as compared to usual care in the context of inpatient rehabilitation. Methods/Design We conducted a multicenter cluster randomized controlled trial in 3 rehabilitation clinics. Clusters are groups of patients with FMS consecutively recruited within one week after admission. Patients of the intervention group receive the advanced multidisciplinary self-management patient education program (considering new knowledge on FMS, with a focus on transfer into everyday life), whereas patients in the control group receive standard patient education programs including information on FMS and coping with pain. A total of 566 patients are assessed at admission, at discharge and after 6 and 12 months, using patient reported questionnaires. Primary outcomes are patients’ disease- and treatment-specific knowledge at discharge and self-management skills after 6 months. Secondary outcomes include satisfaction, attitudes and coping competences, health-promoting behavior, psychological distress, health impairment and participation. Treatment effects between groups are evaluated using multilevel regression analysis adjusting for baseline values. Discussion The study evaluates the effectiveness of a self-management patient education program for patients with FMS in the context of inpatient rehabilitation in a cluster randomized trial. Study results will show whether self-management patient education is beneficial for this group of patients. Trial registration German Clinical Trials Register, DRKS00008782 , Registered 8 July 2015

Measurements are presented of inclusive charm and beauty cross sections in e(+)p collisions at HERA for values of photon virtuality Q(2) > 150 GeV2 and of inelasticity 0.1 < y < 0.7. The charm and beauty fractions are determined using a method based on the impact parameter, in the transverse plane, of tracks to the primary vertex, as measured by the H1 vertex detector. The data are divided into four regions in Q(2) and Bjorken x, and values for the structure functions F-2(c (c) over bar) and F-2(b (b) over bar) are obtained. The results are found to be compatible with the predictions of perturbative quantum chromodynamics.

Inclusive D* production is measured in deep-inelastic ep scattering at HERA with the H1 detector. In addition, the production of dijets in events with a D* meson is investigated. The analysis covers values of photon virtuality 2< Q^2 <=100 GeV^2 and of inelasticity 0.05<= y <= 0.7. Differential cross sections are measured as a function of Q^2 and x and of various D* meson and jet observables. Within the experimental and theoretical uncertainties all measured cross sections are found to be adequately described by next-to-leading order (NLO) QCD calculations, based on the photon-gluon fusion process and DGLAP evolution, without the need for an additional resolved component of the photon beyond what is included at NLO. A reasonable description of the data is also achieved by a prediction based on the CCFM evolution of partons involving the k_T-unintegrated gluon distribution of the proton.