Genetic, Phenotypic and Metabolic Diversity of Yeasts From Wheat Flag Leaves.

The phyllosphere, the aboveground part of a plant, is a harsh environment with diverse abiotic and biotic stresses, including oscillating nutrient availability and temperature as well as exposure to UV radiation. Microbial colonization of this dynamic environment requires specific adaptive traits, including tolerance to fluctuating temperatures, the production of secondary metabolites and pigments to successfully compete with other microorganisms and to withstand abiotic stresses. Here, we isolated 175 yeasts, comprising 15 different genera, from the wheat flag leaf and characterized a selection of these for various adaptive traits such as substrate utilization, tolerance to different temperatures, biofilm formation, and antagonism toward the fungal leaf pathogen Fusarium graminearum. Collectively our results revealed that the wheat flag leaf is a rich resource of taxonomically and phenotypically diverse yeast genera that exhibit various traits that can contribute to survival in the harsh phyllosphere environment.

Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning.

In primary fibroblasts from Leigh Syndrome (LS) patients, isolated mitochondrial complex I deficiency is associated with increased reactive oxygen species levels and mitochondrial morpho-functional changes. Empirical evidence suggests these aberrations constitute linked therapeutic targets for small chemical molecules. However, the latter generally induce multiple subtle effects, meaning that in vitro potency analysis or single-parameter high-throughput cell screening are of limited use to identify these molecules. We combine automated image quantification and artificial intelligence to discriminate between primary fibroblasts of a healthy individual and a LS patient based upon their mitochondrial morpho-functional phenotype. We then evaluate the effects of newly developed Trolox variants in LS patient cells. This revealed that Trolox ornithylamide hydrochloride best counterbalanced mitochondrial morpho-functional aberrations, effectively scavenged ROS and increased the maximal activity of mitochondrial complexes I, IV and citrate synthase. Our results suggest that Trolox-derived antioxidants are promising candidates in therapy development for human mitochondrial disorders.

Quetiapine treatment and improved cognitive functioning in borderline personality disorder.

OBJECTIVE: We aimed to assess whether executive functioning improved over time in a sample of borderline personality disorder (BPD) subjects that took part in a quetiapine treatment trial. METHODS: Performance on the following neurocognitive tasks was assessed at enrolment and at the end of the 12 weeks quetiapine treatment: Trail Making Task, Word Fluency Task and Tower of London Task. Forty-one BPD patients were recruited, of whom 32 completed the trial. An intention-to-treat analysis with a mixed linear model was applied. RESULTS: The data show that participants significantly improved on most executive functioning measures. Patients' scores decreased significantly (mean [SD] difference; p-value) on the Trail Making Task Part A (11.7 [2.3]; p < 0.0001), Part B (51.8 [9.2]; p < 0.0001) and 'B minus A' (40.1 [8.2]; p < 0.0001), on a Phonological (15.9 [1.6]; p < 0.0001) and Semantic (9.8 [1.1]; p < 0.0001) Verbal Fluency tasks, and on the Tower of London total correct score (2.5 [0.4]; p < 0.0001), total move score (29.5 [4.5]; p < 0.0001) and total time (172.9 [35.8]; p < 0.0001). CONCLUSIONS: In this study we have demonstrated that executive functioning in BPD is improved after treatment with quetiapine. Neurocognitive measures of executive functioning should be considered as valuable outcomes in the study of treatment efficacy in BPD.

Efficacy of quetiapine for impulsivity and affective symptoms in borderline personality disorder.

Data on the efficacy of quetiapine in borderline personality disorder (BPD) are still scarce. We aimed to investigate the efficacy of quetiapine for impulsivity and a broad range of affective symptoms in BPD. In this 12-week open-label study, we included individuals with BPD who presented to psychiatric in- and outpatient services. After a gradual titration of quetiapine, a flexible dose (range, 100-800 mg) was administered. The main outcome measures consisted of the scores on patient-rated questionnaires (Barratt Impulsiveness Scale, Buss-Durkee Hostility Inventory, Affective Lability Scale, Spielberger State and Trait Anxiety Inventory, Spielberger State and Trait Anger Inventory, and Beck Depression Inventory) and on neurocognitive tasks related to impulsivity (Stroop Color Word Task and IOWA Gambling Task). A mixed linear model, correcting for age, sex, antidepressant use, and weeks in psychotherapy, was applied. Forty-one patients (34 females and 7 males; mean [SD] age, 27.0 [9.0] years) were enrolled in the study, 32 of which completed the trial. Patients' scores decreased significantly (mean [SD] difference; P value) on the Barratt Impulsiveness Scale (19.7 [2.0]; P < 0.0001), Buss-Durkee Hostility Inventory (11.5 [1.4]; P < 0.0001), Affective Lability Scale (0.75 [0.08]; P < 0.0001), Beck Depression Inventory (25.0 [1.7]; P < 0.0001), Spielberger State and Trait Anxiety Inventory state (19.9 [1.9]; P < 0.0001) and trait (20.8 [1.7]; P < 0.0001) subscale, and Spielberger State and Trait Anger Inventory state (7.3 [1.1]; P < 0.0001) and trait (10.1 [1.0]; P < 0.0001) subscale. In addition, patients showed significantly less inference on the Stroop Color Word Task and had more 'good choices' on the IOWA Gambling Task. These results suggest that quetiapine may be efficacious in the treatment of impulsivity and affective symptoms in BPD.