The histone deacetylase Hda1 affects oxidative and osmotic stress response as well as mycoparasitic activity and secondary metabolite biosynthesis in Trichoderma atroviride.

The mycoparasitic fungus Trichoderma atroviride is applied in agriculture as a biostimulant and biologic control agent against fungal pathogens that infest crop plants. Secondary metabolites are among the main agents determining the strength and progress of the mycoparasitic attack. However, expression of most secondary metabolism-associated genes requires specific cues, as they are silent under routine laboratory conditions due to their maintenance in an inactive heterochromatin state. Therefore, histone modifications are crucial for the regulation of secondary metabolism. Here, we functionally investigated the role of the class II histone deacetylase encoding gene hda1 of T. atroviride by targeted gene deletion, phenotypic characterization, and multi-omics approaches. Deletion of hda1 did not result in obvious phenotypic alterations but led to an enhanced inhibitory activity of secreted metabolites and reduced mycoparasitic abilities of T. atroviride against the plant-pathogenic fungi Botrytis cinerea and Rhizoctonia solani. The ∆hda1 mutants emitted altered amounts of four volatile organic compounds along their development, produced different metabolite profiles upon growth in liquid culture, and showed a higher susceptibility to oxidative and osmotic stress. Moreover, hda1 deletion affected the expression of several notable gene categories such as polyketide synthases, transcription factors, and genes involved in the HOG MAPK pathway.IMPORTANCEHistone deacetylases play crucial roles in regulating chromatin structure and gene transcription. To date, classical-Zn2+ dependent-fungal histone deacetylases are divided into two classes, of which each comprises orthologues of the two sub-groups Rpd3 and Hos2 and Hda1 and Hos3 of yeast, respectively. However, the role of these chromatin remodelers in mycoparasitic fungi is poorly understood. In this study, we provide evidence that Hda1, the class II histone deacetylases of the mycoparasitic fungus Trichoderma atroviride, regulates its mycoparasitic activity, secondary metabolite biosynthesis, and osmotic and oxidative stress tolerance. The function of Hda1 in regulating bioactive metabolite production and mycoparasitism reveals the importance of chromatin-dependent regulation in the ability of T. atroviride to successfully control fungal plant pathogens.

Willingness to pay for a quality-adjusted life year for depressive disorders compared to heart disease based on population preferences.

PURPOSE: According to estimations of the World Health Organization, depressive disorders, and cardiovascular disease will be the leading causes for global burden of disease in 2030. The aim of the present study was to estimate the value a representative sample of the German population places on quality-adjusted life years (QALYs) for depressive disorders compared to heart disease. METHODS: A representative sample of N = 967 of the German general public was randomly presented with one of two hypothetical health-loss scenarios: One version of the questionnaire presented respondents with health loss due to depression, while the other version dealt with health loss due to experiencing a heart disease. Respondents were asked to indicate their willingness to pay (WTP) for four hypothetical health-gain scenarios with different treatment options. RESULTS: In the depression questionnaire median WTP values ranged from 1000 to 1500 EUR; in the heart disease questionnaire from 1000 to 2000 EUR. Results of the Mann-Whitney U-Test and Median Test indicate higher WTP values for heart disease compared to depressive disorders when QALY gains were minor and stretched over a long period of time, and when treatment with bypass operation (rather than treatment with ECT) was offered. Zero WTP was significantly higher in all scenarios of the depression questionnaire in comparison to the hearth disease questionnaire. CONCLUSION: Results indicate that respondents valued the necessity of paying for treatment higher when presented with heart disease compared to depression.

Monetary Valuation of a Quality-Adjusted Life Year (QALY) for Depressive Disorders Among Patients and Non-Patient Respondents: A Matched Willingness to Pay Study.

Background: As estimated by the World Health Organization, depressive disorders will be the leading contributor to the Global Burden of Disease by 2030. In light of this fact, we designed a study whose aim was to investigate whether the value placed on health-related quality of life (HRQoL) for a depressive disorder is higher in patients diagnosed with a major depressive disorder (MDD) compared to non-patients in a matched sample. Method: We collected data on willingness to pay (WTP) for a total of four health-gain scenarios, which were presented to 18 outpatients diagnosed with a MDD versus 18 matched non-patient respondents with no symptoms of depression. Matching characteristics included age, income, level of education, and type of health insurance. Respondents were presented with different HRQoL scenarios in which they could choose to pay money to regain their initial health state through various treatment options (e.g., inpatient treatment, electroconvulsive therapy). To test whether the probability of stating a positive WTP differed significantly between the two samples, Fisher's exact test was used. Differences regarding stated WTP between the samples were investigated using the Mann-Whitney U-test. Results: For most of the health scenarios, the probability of stating a positive WTP did not differ between the two samples. However, patient respondents declared WTP values up to 7.4 times higher than those stated by matched non-patient respondents. Conclusion: Although the perceived necessity to pay for mental-HRQoL gains did not differ between respondents with MDD and respondents with no symptoms of depression, patient respondents stated higher values.

Value of Electroconvulsive Therapy in the General Public: A Willingness to Pay Study in Germany.

OBJECTIVE: The aims of this study were to estimate the value a population-representative sample places on electroconvulsive therapy (ECT) through willingness to pay (WTP) and to assess the effects of individual characteristics on WTP for ECT. METHODS: A German population-representative sample of 518 was presented with a hypothetical health loss scenario of depression and was asked to indicate WTP for ECT. Probit and quantile regression were used to estimate the effects of individual characteristics on the probability of stating a positive WTP and on the amount of money respondents were willing to pay. RESULTS: Two thirds of respondents stated that they had no knowledge about ECT. Most (56.5%) respondents indicated zero WTP for health gains through ECT treatment. Mean WTP was €5201 ($5612); median WTP was €1000 ($1079). Respondents' monthly household income had a significant effect on the probability of stating a positive WTP. Assessing WTP above zero, income showed a significant positive effect, whereas a higher score of depressive complaints showed a significant negative effect on the amount respondents were willing to pay. CONCLUSION: Knowledge about ECT treatment is particularly low in the German public.