Fast and easy bioassay for the necrotizing fungus Botrytis cinerea on poplar leaves.

BACKGROUND: Necrotizing pathogens pose an immense economic and ecological threat to trees and forests, but the molecular analysis of these pathogens is still in its infancy because of lacking model systems. To close this gap, we developed a reliable bioassay for the widespread necrotic pathogen Botrytis cinerea on poplars (Populus sp.), which are established model organisms to study tree molecular biology. RESULTS: Botrytis cinerea was isolated from Populus x canescens leaves. We developed an infection system using fungal agar plugs, which are easy to handle. The method does not require costly machinery and results in very high infection success and significant fungal proliferation within four days. We successfully tested the fungal plug infection on 18 poplar species from five different sections. Emerging necroses were phenotypically and anatomically examined in Populus x canescens leaves. We adapted methods for image analyses of necrotic areas. We calibrated B. cinerea DNA against Ct-values obtained by quantitative real-time polymerase chain reaction and measured the amounts of fungal DNA in infected leaves. Increases in necrotic area and fungal DNA were strictly correlated within the first four days after inoculation. Methyl jasmonate pretreatment of poplar leaves decreased the spreading of the infection. CONCLUSIONS: We provide a simple and rapid protocol to study the effects of a necrotizing pathogen on poplar leaves. The bioassay and fungal DNA quantification for Botrytis cinerea set the stage for in-depth molecular studies of immunity and resistance to a generalist necrotic pathogen in trees.

Substitution of Copper by Magnesium in Malachite: Insights into the Synthesis and Structural Effects.

The phase width of the copper hydroxycarbonate malachite, Cu2CO3(OH)2, upon substitution with magnesium has been studied in detail. In extension of a previous study on amorphous precursors, the introduction of a hydrothermal aging step allowed the retrieval of crystalline hydroxycarbonate samples with up to 37 atom % Mg (metal content) that are suitable candidates as precursors to Cu/MgO catalysts for CO hydrogenation. Simultaneous refinements of X-ray powder diffraction and pair distribution function (PDF) data as well as complementary spectroscopic insight (X-ray absorption and infrared spectroscopy) revealed that samples with up to 18 atom % Mg are phase-pure magnesian malachites but the magnesium content can be increased beyond this threshold when mcguinnessite (CuMgCO3(OH)2) is accepted as a side phase. In a complementary study, a continuous increase of the magnesium fraction was found during aging and the corresponding structural evolution was studied by means of PDF. These findings add significant insight into the aging chemistry of crystalline Cu,Mg hydroxycarbonates. Furthermore, both phase-pure magnesian malachite and mcguinnessite-containing samples with up to 37 atom % Mg have been examined by thermogravimetry, X-ray powder diffraction, and N2 physisorption and were found to be promising candidates for use as precursors for the preparation of Cu/MgO catalysts.

Pulmonary affection of patients with Pseudoxanthoma elasticum: Long-term development and genotype-phenotype-correlation.

Pseudoxanthoma elasticum (PXE) is a rare, heritable disease caused by various, mainly recessively transmitted mutations in the ABCC6 gene. Due to calcification of soft connective tissue phenotypic hallmarks are progressive loss of vision, alternation of the skin and early onset atherosclerosis. Beside these main features patients also suffer from impaired alveolar diffusion. The present study focused on impaired lung functioning based on a large cohort of patients with PXE, its long-term development, and genotype-phenotype correlation. Retrospectively, 98 patients and 45 controls were enrolled. All patients underwent body plethysmography and carbon monoxide diffusion testing. Of 35 patients three or more body plethysmographic records were available for long-term analysis. For genotype-phenotype analysis ABCC6 genotypes were grouped as two missense, mixed, or two nonsense mutations. Patients with PXE showed significantly reduced vital capacity (p < 0.05), diffusion capacity (p < 0.01), and diffusion transfer coefficient (p < 0.05). Over a mean period of 38 months diffusion capacity (p < 0.05) and diffusion transfer coefficient (p < 0.01) dropped significantly whereas lung volumes remained unchanged. Genotype-phenotype correlation revealed no connection between gene variants and lung functioning. In conclusion, PXE is accompanied by progressive reduction of alveolar diffusion indicating progressive alterations of lung tissue. Genotype-phenotype correlation with genotypes sorted as missense and nonsense mutations do not explain impaired lung functioning.

Feasibility of a Multimodal Telemedical Intervention for Patients with Parkinson's Disease-A Pilot Study.

Symptoms of Parkinson's disease (PD) can be controlled well, but treatment often requires expert judgment. Telemedicine and sensor-based assessments can allow physicians to better observe the evolvement of symptoms over time, in particular with motor fluctuations. In addition, they potentially allow less frequent visits to the expert's office and facilitate care in rural areas. A variety of systems with different strengths and shortcomings has been investigated in recent years. We designed a multimodal telehealth intervention (TelePark) to mitigate the shortcomings of individual systems and assessed the feasibility of our approach in 12 patients with PD over 12 weeks in preparation for a larger randomized controlled trial. TelePark uses video visits, a smartphone app, a camera system, and wearable sensors. Structured training included setting up the equipment in patients' homes and group-based online training. Usability was assessed by questionnaires and semi-standardized telephone interviews. Overall, 11 out of 12 patients completed the trial (5 female, 6 male). Mean age was 65 years, mean disease duration 7 years, mean MoCA score 27. Adherence was stable throughout the study and 79% for a short questionnaire administered every second day, 62% for medication confirmation, and 33% for an electronic Hauser diary. Quality of life did not change in the course of the study, and a larger cohort will be required to determine the effect on motor symptoms. Interviews with trial participants identified motivations to use such systems and areas for improvements. These insights can be helpful in designing similar trials.

Interpersonal Musical Synchronization and Prosocial Behavior in Children: No Effects in a Controlled Field Experiment.

Prosocial effects of music have recently attracted increased attention in research and media. An often-cited experiment, carried out by Kirschner and Tomasello in 2010 under laboratory conditions, found that children at the age of four years were more willing to help each other after they had engaged in synchronous musical activities. The aim of the current study was to replicate this research under controlled field conditions in the children's social environment, and to disentangle the musical synchronization effect by introducing a verbal interaction (singing together) and a motor interaction (tapping together) task, contrasted by an asynchronous control condition. In a between-participants design, no effects of musical synchronization nor the children's gender were found. Furthermore, age was not related to prosocial behavior. Explanations are systematically discussed, yet it remains possible that the original effect found in 2010 might be overestimated and less consistently reproducible as previously assumed.

Pacritinib protects dendritic cells more efficiently than ruxolitinib.

Targeting Janus kinase (JAK) has revolutionized the treatment of myeloproliferative neoplasms. The JAK inhibitor ruxolitinib has improved the outcome and quality of life of patients dramatically at the cost of increased risk of infections. As previously reported, ruxolitinib severely impairs the differentiation of peripheral blood mononuclear cells to monocyte-derived dendritic cells and inhibits the function of dendritic cells in vitro and in vivo, which expanded its use as an immunomodulatory compound. Pacritinib is a novel JAK inhibitor that will soon be approved for the treatment of myeloproliferative neoplasms, and early results are promising. We investigated the impact of the novel JAK inhibitor pacritinib on the function of monocyte-derived dendritic cells and compared it with that of ruxolitinib. In contrast to ruxolitinib, pacritinib exhibits only mild suppressive effects on dendritic cells. The upregulation of activation markers and CCR7 after TLR4 ligation is not or is only marginally affected by pacritinib. Pacritinib, at concentrations reflecting patients' plasma levels, reduces interleukin (IL)-12 secretion, whereas IL-6 and tumor necrosis factor α levels are unchanged at this concentration. In conclusion, the immunosuppressive effect of pacritinib on dendritic cells is significantly less pronounced than the effect of ruxolitinib. Therefore, our data may help to identify those patients with myelofibrosis who may benefit from pacritinib treatment.

Rheumatologic diseases impact the risk of progression of MGUS to overt multiple myeloma.

Monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition, is associated with various chronic inflammatory rheumatic diseases (RDs) and is frequently observed as an incidental finding during routine work-up. The association of MGUS and chronic RDs is well established, but the impact of RDs on the risk of transformation into overt multiple myeloma (MM) has not been evaluated so far. MGUS patients diagnosed between January 2000 and August 2016 were identified and screened for concomitant RDs. RDs were grouped into antibody (Ab)-mediated RDs and non-Ab-mediated RDs (polymyalgia rheumatica, large-vessel giant cell arteritis, spondyloarthritis, and gout). Progression to MM was defined as a categorical (yes/no) or continuous time-dependent (time to progression) variable. Of 2935 MGUS patients, 255 (9%) had a concomitant RD. MGUS patients diagnosed with non-Ab-mediated RDs had a doubled risk of progression compared with those without a concomitant RD (hazard ratio, 2.1; 95% CI, 1.1-3.9; P = .02). These data translate into a 5-year risk of progression of 4% in MGUS patients without rheumatologic comorbidity, 10% in those with concomitant non-Ab-mediated RDS, and 2% in those with Ab-mediated RDs. By using the complex risk stratification model that includes myeloma protein (M-protein) concentration, immunoglobulin type, and level of free light chain ratio as variables, patients with non-Ab-mediated RDs (n = 57) had the highest risk for progression (hazard ratio, 6.8; 95% CI, 1.5-30.7; P = .01) compared with patients with Ab-mediated RDs (n = 77). Chronic inflammatory diseases have an impact on the risk of MGUS progressing into overt MM, with a doubled risk of transformation observed in patients with non-Ab-mediated RDs. Future research can elucidate whether comorbidities such as RDs should be included in currently applied prognostic MGUS scores.

"Overcoming the Fear That Haunts Your Success" - The Effectiveness of Interventions for Reducing the Impostor Phenomenon.

The impostor phenomenon (IP) refers to intense thoughts of fraudulence reported by high-achieving individuals. Since it has been shown to account for several personal and work-related complications, effective interventions are greatly needed. Against the background of mindset theory, we developed and tested two mindset interventions. We evaluated the impact of a coaching and a training intervention adopting a randomized controlled outcome design. One hundred and three young employees were randomly assigned to receive coaching (n = 36), training (n = 33), or no intervention (n = 34). Results reveal that coaching was an effective mindset intervention for sustainably reducing IP scores. Fear of negative evaluation emerged to mediate the relation between the coaching intervention and the reduced IP scores significantly. Moreover, coaching improved self-enhancing attributions and self-efficacy and reduced the tendency to cover up errors as well as the fear of negative evaluation. Training was superior in regard to knowledge acquisition. Specific implications are discussed.

FVIII half-life extension by coadministration of a D'D3 albumin fusion protein in mice, rabbits, rats, and monkeys.

A novel mechanism for extending the circulatory half-life of coagulation factor VIII (FVIII) has been established and evaluated preclinically. The FVIII binding domain of von Willebrand factor (D'D3) fused to human albumin (rD'D3-FP) dose dependently improved pharmacokinetics parameters of coadministered FVIII in all animal species tested, from mouse to cynomolgus monkey, after IV injection. At higher doses, the half-life of recombinant FVIII (rVIII-SingleChain) was calculated to be increased 2.6-fold to fivefold compared with rVIII-SingleChain administered alone in rats, rabbits, and cynomolgus monkeys, and it was increased 3.1-fold to 9.1-fold in mice. Sustained pharmacodynamics effects were observed (ie, activated partial thromboplastin time and thrombin generation measured ex vivo). No increased risk of thrombosis was observed with coadministration of rVIII-SingleChain and rD'D3-FP compared with rVIII-SingleChain alone. At concentrations beyond the anticipated therapeutic range, rD'D3-FP reduced the hemostatic efficacy of coadministered rVIII-SingleChain. This finding might be due to scavenging of activated FVIII by the excessive amount of rD'D3-FP which, in turn, might result in a reduced probability of the formation of the tenase complex. This observation underlines the importance of a fine-tuned balance between FVIII and its binding partner, von Willebrand factor, for hemostasis in general.

Disease activity-dependent expression of nerve growth factor TRKA and P75 receptors on elevated dendritic cells and peripheral leucocytes in patients with systemic lupus erythematosus.

INTRODUCTION: The nervous system modulates rheumatic diseases in neurogenic inflammation (NI). Nerve growth factor (NGF) plays a pivotal role in NI and chronic nociceptive pain. However, the role of NGF in autoimmune inflammatory diseases is not well understood. The aim of this study was to analyse NGF high- (TrkA) and low-affinity (p75) receptors on all major leucocyte subsets of patients with systemic lupus erythematosus (SLE) as a potential indicator of NI. METHODS: A total of 13 patients were analysed by fluorescence-activated cell sorting and compared to 13 healthy control (HC) subjects. Patients were also stratified for high or low disease activity (CRP, ESR, SLEDAI, ANA, anti-dsDNA and C3/C4). Statistics included the Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: When comparing patients and HC, TrkA was not differentially expressed. In contrast, p75 was increased on CD16+ and CD56+ leucocytes in patients. CD11c+ dendritic cells (DC) were in total increased in SLE. DCs were also significantly elevated in active patients. Furthermore, we found an intermediate CD11b+ population strongly expressing TrkA in patients and HC. CONCLUSION: We demonstrate for the first time differential NGF receptor expression in SLE. The increased CD11c+ DCs might indicate additional activation in SLE.

Computerized Cognitive Training in Multiple Sclerosis: A Systematic Review and Meta-analysis.

Background. Cognitive impairments are common in people with multiple sclerosis (MS). Systematic reviews reported promising evidence for various cognitive interventions in this population. Computerized cognitive training (CCT) has strong evidence for safety and efficacy in several populations, but its effects in MS have yet to be specified. Objective. We aimed to synthesize the evidence from randomized controlled trials (RCTs) investigating the effects of CCT on cognitive, psychosocial, and functional outcomes in adults with MS. Method. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL from inception to March 2019. We calculated standardized mean difference (Hedges' g) of change from baseline in untrained measures of cognition, individual domains, psychosocial functioning, and daily function between CCT and control groups using a random-effects model. Results. A total of 20 RCTs encompassing 982 participants (78% with relapsing-remitting MS) were included. The overall cognitive effect size was moderate (g = 0.30; 95% CI = 0.18-0.43), with no evidence of small-study effect or between-study heterogeneity (prediction interval = 0.17-0.44). Small to moderate effect sizes were found for attention/processing speed, executive functions, and verbal and visuospatial memory. Evidence for working memory, fatigue, and psychosocial and daily functioning were inconclusive. Cognitive effects waned without further training. Conclusions. CCT is efficacious for overall and key cognitive domains in adults with MS, but efficacy on other outcomes and in progressive subtypes remains unclear. Long-term and well-powered trials with diverse cohorts are needed to optimize and maintain the efficacy of CCT, investigate transfer to daily living, and determine who can benefit and whether CCT is a cost-effective strategy to attenuate cognitive decline in MS.

Patients with Idiopathic Membranous Nephropathy: A Real-World Clinical and Economic Analysis of U.S. Claims Data.

BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in nondiabetic adults. Approximately one third of patients with MN progress to end-stage renal disease (ESRD), while others may be successfully treated to remission. Patients with MN represent a high-risk population for whom management strategies can alter and improve outcomes. Currently, there is little real-world evidence regarding the burden of MN on health plans. OBJECTIVES: To (a) characterize clinical and economic outcomes during a 1-year time frame among a prevalent cohort of patients with MN and (b) compare the 5% of patients incurring the highest cost with the remaining 95%. METHODS: A retrospective analysis of commercially insured patients was conducted using MarketScan administrative health care claims data from January 1, 2012, to December 31, 2015. Patients were aged ≥ 18 years, enrolled In a fee-for-service plan, and had ≥ 2 medical claims for an MN diagnosis (ICD-9-CM codes 581.1, 582.1, and 583.1). Diagnoses indicating clear secondary causes were excluded wherever possible. Demographics were determined as of the first diagnosis date; clinical characteristics (e.g., MN-specific therapy, complications, and procedures), health care resource utilization (HCRU; inpatient, outpatient including other outpatient and emergency department [ED], and prescriptions), and costs were evaluated for 1 year following MN diagnosis. Total costs and cost distribution (2017 U.S. dollars) were examined using plan-paid and patient-paid amounts. The 95th percentile was used to categorize and compare the subcohorts: high-cost cohort (HCC) patients (top 5%) and non-high-cost cohort (NHCC) patients (the remaining 95%). Descriptive analyses, chi-square tests, and Wilcoxon rank-sum tests were conducted. RESULTS: 2,689 patients were identified (60.0% male, mean age = 46.4 years). Severity and advanced disease were observed In a higher proportion of HCC patients (n = 134) versus NHC patients (n = 2,555) via adverse health outcomes, procedures, and immunosuppressant use. HCC patients used significantly more resources on average than NHCC patients (additional use): 1.7 inpatient, 1.2 ED, and 4.8 outpatient office visits; 15 prescriptions; and 64.8 other outpatient visits (i.e., outpatient, hospital, and ESRD facilities). Total MN-related cost and mean (SD) cost per patient were $123.2 million and $45,814 ($101,353); HCC patients accounted for 43.7% of total costs for a mean cost per patient of $401,608 versus NHCC patients at 56.3% and mean cost per patient of $27,154. The greatest costs for both groups were related to outpatient visits (HCC = 46.7%; NHCC = 52.8%), inpatient visits (HCC = 27.7%; NHCC = 28.6%), and prescriptions (HCC = 25.7%; NHCC = 18.6%). CONCLUSIONS: Patients with MN are significantly burdened with high disease severity and adverse health outcomes, resulting In substantial HCRU and costs. Health plan cost drivers for MN (HCC and NHCC patients) occurred primarily In the outpatient setting, followed by the inpatient setting and prescriptions. Modifiable aspects preceding progression to advanced renal disease and worse outcomes should be explored to Identify effective interventions and improve resource allocation earlier In the disease pathway, before ESRD. DISCLOSURES: This study was funded by Mallinckrodt Pharmaceuticals. Kirkemo, Pavlova-Wolf, and Bartels-Peculis are employees and stockholders of Mallinckrodt Pharmaceuticals. Nazareth was an employee of Mallinckrodt Pharmaceuticals at the time of this study. Kariburyo, Xie, and Vaidya are employees of STATinMED Research, a paid consultant to Mallinckrodt Pharmaceuticals. Sim received an investigator-initiated research grant from Mallinkcrodt Pharmaceuticals. A portion of the study results were previously presented at the American Society of Nephrology (ASN) Kidney Week 2017; November 2, 2017; New Orleans, LA.

Phenotypic characterization of haemophilia B - Understanding the underlying biology of coagulation factor IX.

Haemophilia B is a recessive, X-linked bleeding disorder due to inherited deficiency in vitamin K-dependent coagulation factor IX (FIX). FIX activity levels, as a basis for the definition of disease severity, do not clearly correlate with bleeding phenotype, likely due to the multiple steps regulating coagulation. Timely, with the availability of extended half-life products and successful steps in gene therapy, haemophilia B therapy is in an active developmental phase. Therefore, increased knowledge of the factors contributing to the variation of haemostatic and clinical outcome and response to therapy is welcomed. FIX acts at the crossroads of both the extrinsic and intrinsic pathways, and on the platelet procoagulant membrane at the site of vascular injury, and therefore, FIX biology is targeted for multiple effectors and regulators. The synthesis, cellular and molecular interactions, and elimination routes of FIX are not as well studied as for FVIII. The specific roles of magnesium in both platelet adhesion and FIX activation, and of vascular collagen at the haemostatic site of platelet adhesion and FIX residence are of particular interest. Biochemical and translational research on these issues should improve our understanding of the mechanisms involved, leading to the development of relevant assays that measure both haemostasis and treatment response. The latter is becoming increasingly important in the new era of haemophilia management and ultimately may lead to improved treatment strategies individually tailored to a patient's needs and cost-efficiency.

Curious Case of 2-Selenouracil: Efficient Population of Triplet States and Yet Photostable.

Excited-state MS-CASPT2 and ADC(2) quantum chemical calculations and nonadiabatic dynamics simulations show that 2-selenouracil is able to both efficiently populate and depopulate reactive triplet states in an ultrashort time scale. Thus, the heavier homologue of 2-thiouracil unites the ultrafast, high-yield intersystem crossing of 2-thiouracil with the short excited-state lifetime and photostability of the parent nucleobase uracil-two properties that have been traditionally thought to be diametrically opposed. Remarkably, while the S2 → S1 → T2 → T1 deactivation dynamics of 2-selenouracil is analogous to that of 2-thiouracil, the calculations show that the triplet lifetime of 2-selenouracil should decrease by up to 3 orders of magnitude in comparison to that 2-thiouracil, possibly down to the few-picosecond time scale. The main reasons for this decrease are the lack of a second T1 minimum, the enhanced spin-orbit coupling, and the reduction of the energy barrier to access the T1/ S0 crossing-in particular in aqueous solution-compared to 2-thiouracil. Such unusual photophysical properties, together with its significant red-shifted absorption spectrum, could make 2-selenouracil a useful specialized photosensitizer for photodynamical therapy.

Comparative transcriptome of neurons after oxygen-glucose deprivation: Potential differences in neuroprotection versus reperfusion.

In the context of ischemic stroke, rescuing neurons can be theoretically achieved with either reperfusion or neuroprotection. Reperfusion works via the rapid restoration of oxygen and glucose delivery. Neuroprotection comprises molecular strategies that seek to block excitotoxicity, oxidative stress or various cell death pathways. Here, we propose the hypothesis that neurons rescued with reperfusion are different from neurons rescued with molecular neuroprotection. Neurons were subjected to oxygen-glucose deprivation (OGD) and then treated with "in vitro reperfusion" (i.e. energetic rescue via restoration of oxygen and glucose) or Z-VADfmk (to block apoptosis) or MK-801 (to block excitotoxicity). Levels of injury were titrated so that equivalent levels of neuronal salvage were achieved with reperfusion or neuroprotection. Gene arrays showed that OGD significantly altered the transcriptomic profiles of surviving neurons. Pathway analysis confirmed that a large spectrum of metabolic, inflammation, and signaling genes were perturbed. In spite of the fact that equal levels of neuronal salvage were achieved, energetic rescue renormalized the transcriptomic profiles in surviving neurons to a larger degree compared to neuroprotection with either Z-VADfmk or MK-801. These findings suggest that upstream reperfusion may bring salvaged neurons back "closer to normal" compared to downstream molecular neuroprotection.

Different in the dark: The effect of habitat characteristics on community composition and beta diversity in bromeliad microfauna.

The mechanisms which structure communities have been the focus of a large body of research. Here, we address the question if habitat characteristics describing habitat quality may drive changes in community composition and beta diversity of bromeliad-inhabiting microfauna. In our system, changes in canopy cover along an environmental gradient may affect resource availability, disturbance in form of daily water temperature fluctuations and predation, and thus may lead to changes in community structure of bromeliad microfauna through differences in habitat quality along this gradient. Indeed, we observed distinct changes in microfauna community composition along the environmental gradient explained by changes in the extent of daily water temperature fluctuations. We found beta diversity to be higher under low habitat quality (low canopy cover) than under high habitat quality (high canopy cover), which could potentially be explained by a higher relative importance of stochastic processes under low habitat quality. We also partitioned beta diversity into turnover and nestedness components and we found a nested pattern of beta diversity along the environmental gradient, with communities from the lower-quality habitat being nested subsets of communities from the higher-quality habitat. However, this pattern resulted from an increase in microfauna alpha diversity with an increase in habitat quality. By providing insights into microfauna-environment relationships our results contribute to the mechanistic understanding of community dynamics in small freshwater bodies. Here, we highlight the importance of habitat characteristics representing habitat quality in structuring communities, and suggest that this information may help to improve conservation practices of small freshwater ecosystems.

Neuromyths in Music Education: Prevalence and Predictors of Misconceptions among Teachers and Students.

In the last decade, educational neuroscience has become increasingly important in the context of instruction, and its applications have been transformed into new teaching methods. Although teachers are interested in educational neuroscience, communication between scientists and teachers is not always straightforward. Thus, misunderstandings of neuroscientific research results can evolve into so-called neuromyths. The aim of the present study was to investigate the prevalence of such music-related neuromyths among music teachers and music students. Based on an extensive literature research, 26 theses were compiled and subsequently evaluated by four experts. Fourteen theses were selected, of which seven were designated as scientifically substantiated and seven as scientifically unsubstantiated (hereafter labeled as "neuromyths"). One group of adult music teachers (n = 91) and one group of music education students (n = 125) evaluated the theses (forced-choice discrimination task) in two separate online surveys. Additionally, in both surveys person-characteristic variables were gathered to determine possible predictors for the discrimination performance. As a result, identification rates of the seven scientifically substantiated theses were similar for teachers (76%) and students (78%). Teachers and students correctly rejected 60 and 59%, respectively, of the seven neuromyths as scientifically unsubstantiated statements. Sensitivity analysis by signal detection theory revealed a discrimination performance of d' = 1.25 (SD = 1.12) for the group of teachers and d' = 1.48 (SD = 1.22) for the students. Both groups showed a general tendency to evaluate the theses as scientifically substantiated (teachers: c = -0.35, students: c = -0.41). Specifically, buzz words such as "brain hemisphere" or "cognitive enhancement" were often classified as correct. For the group of teachers, the best predictor of discrimination performance was having read a large number of media about educational neuroscience and related topics (R2 = 0.06). For the group of students, the best predictors for discrimination performance were a high number of read media and the hitherto completed number of semesters (R2 = 0.14). Our findings make clear that both teachers and students are far from being experts on topics related to educational neuroscience in music and would therefore benefit from current education-related research in psychology and neuroscience.

Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging.

Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

JAK/STAT disruption induces immuno-deficiency: Rationale for the development of JAK inhibitors as immunosuppressive drugs.

Cytokines are mediating immune cells responses through the activation of the JAK/STAT signaling pathway. Being critical for immune cells, a defective JAK/STAT signaling leads to various immune disorders, such as immunodeficiency. In contrast, hyperactivation of JAK/STAT signaling is linked to autoimmunity and cancer. Targeting the JAK/STAT proteins by small protein inhibitors impedes immune cell function by uncoupling cells from cytokine effects and by interfering with functional immune cell hallmarks, such as cell migration. This review will explore immune syndromes driven by JAK/STAT deregulation and discuss the emerging role of JAK inhibitors as immunosuppressive drugs used in autoimmunity and transplantation medicine.