Einfluss des Pathogengenotyps auf die antagonistische Wirksamkeit von <i>Ulocladium atrum</i> gegen <i>Botrytis cinerea</i>

Der Pilz Botrytis cinerea (Pers.) ist ein weltweit verbreitetes nekrotrophes Pathogen mit einem großen Wirtsspektrum, verbunden mit hohen wirtschaftlichen Schäden. Wiederholte Anwendungen von Fungiziden mit dem gleichen Wirkmechanismus führen rasch zum Auftreten von resistenten Stämmen. Biologische Verfahren können daher eine Alternative bzw. Ergänzung zur chemischen Bekämpfung sein und ebenso zu einem Resistenzmanagement von Fungiziden genutzt werden. Der saprophytische Hyphomycet Ulocladium atrum wurde als Antagonist gegen den Erreger des Grauschimmels bereits an verschiedenen Kulturpflanzen beschrieben. Die antagonistische Wirksamkeit beruht auf der konkurrierenden Besiedlung von nekrotischem Pflanzengewebe, wodurch die epidemische Entwicklung von B. cinerea beeinflusst wird. In der vorliegenden Arbeit wurde die Wirksamkeit von U. atrum gegen verschiedene Genotypen von B. cinerea untersucht. Die verwendeten Pathogengenotypen wurden nach morphologischen und physiologischen Eigenschaften, sowie ihrer Sensitivität gegen Wirkstoffe verschiedener botrytizider Wirkstoffklassen differenziert. Die antagonistische Wirksamkeit von U. atrum konnte sowohl unter kontrollierten Bedingungen auf nekrotischen Rebenblättern, im Gewächshaus an Begonien-, Paprika- und Rebenjungpflanzen, sowie in mehrjährigen Erhebungen unter praktischen Anbaubedingungen an verschiedenen Standorten und Rebsorten im Weinbau nachgewiesen werden. Der Pathogengenotyp von B. cinerea hatte großen Einfluss auf die antagonistische Wirksamkeit von U. atrum. Dieser Einfluss stand jedoch nicht in Zusammenhang mit isolatspezifischen Eigenschaften, wie der Sporengröße, dem Wachstumsverhalten, der Aggressivität oder der Fungizidsensitivität. Desweiteren war eine geeignete Gestaltung von Ausbringungsparametern, wie dem Zeitpunkt, der Häufigkeit und der Sporendichte von U. atrum wichtig, aber auch das Anzuchtnährmedium war von erheblicher Bedeutung. Bei einer Etablierung des Antagonisten im Pflanzenbestand konnte weder ein negativer Einfluss auf die Entwicklung und Ertragsbildung der Kulturpflanze noch auf den Ausbau und die Qualität des Weines beobachtet werden. Durch eine befallsorientierte Staffelung von Anwendungen aus U. atrum und Fenhexamid konnte der Grauschimmelbefall der Trauben signifikant reduziert und zusätzlich der Botrytizideinsatz gemindert werden. Bei hohem Befallsdruck, wie im Jahr 2000, konnte mit U. atrum aufgrund der rasanten Entwicklung von B. cinerea an den Trauben keine signifikante Reduktion des Grauschimmels erzielt werden. Durch die geringe Sensitivität des Antagonisten gegen Pflanzenschutzmittel ist eine Integration in praxisübliche Pflanzenschutzmaßnahmen.Influence of pathogen genotype on the antagonistic efficacy of Ulocladium atrum in the control of Botrytis cinerea The necrotrophic fungus Botrytis cinerea (Pers.) is a pathogen with a wide host range causing economical losses in many crops worldwide. Effective control of the pathogen using fungicides with the same mode of action is restricted by the fast development of resistant isolates. Biocontrol may offer a supplementary or alternative crop protection tool and also can be used for the management of fungicide resistance. The saprophytic hyphomycete Ulocladium atrum has been described for its antagonistic potential against gray mould in various crops. The efficacy of U. atrum depends on the saprophytical competition with B. cinerea during the colonization of necrotic plant tissue, affecting the epidemic spread of the multicyclic pathogen. In this work the efficacy of U. atrum in the biocontrol of various genotypes of B. cinerea was investigated. The strains were differentiated for their morphological and physiological characteristics, as well as on their sensitivity against common botryticides from different chemical groups. The antagonistic potential of U. atrum has been proven under controlled conditions on necrotic grapevine leaves, in greenhouse crops such as begonia, sweat pepper and grapevine plantlings as well as under field conditions in grapes on different cultivars and at several locations over several years. The aggressiveness of B. cinerea strains differed in various crops indicating specific interactions between pathogen and host species. The efficacy of the antagonist U. atrum was also influenced by the genotype of the pathogen strain to be controlled. The differences in vulnerability to the antagonistic activity of U. atrum were neither correlation to strain specific characteristics like spore size, growth or aggressiveness nor to fungicide sensitivity. Furthermore, efficacy of disease control depended on the reasonable coordination of application parameters like spore concentration applied, timing and number of U. atrum applications, as well as the growth media used for spore production of the antagonist. Neither the crop development nor the quality of the wine fermentation was negatively affected by the application of U. atrum. Alternate applications of U. atrum and the botryticide fenhexamid reduced the gray mould infection on berries significantly, whereby the number and dosage of fungicides decreased. However, at high disease pressure like in 2000, the efficacy of U. atrum was not able to reduce significantly the rapid spread of B. cinerea on the grapes, because the incidence of U. atrum on berries decreased before harvest and the antagonistic activity depending on nutrient competition became insufficient. The antagonist showed low sensitivity against pesticides and may be integrated in existing crop protection strategies in viniculture

A Prospective, Randomized, Double-blind, Vehicle-controlled, Multi-centre Clinical Trial of Efficacy, Safety and Local Tolerability

This study was a prospective, parallel-group, randomized, double-blind, vehicle-controlled, multi-centre clinical trial to compare the efficacy of topical sertaconazole 2% cream with vehicle in reducing chronic pruritus in subjects with atopic dermatitis, and to assess its safety and local tolerability. A total of 70 subjects applied either of the 2 treatments twice daily for a period of 4 weeks on affected, itchy skin areas. Treatment efficacy was evaluated primarily considering the item itch intensity on a 5-point verbal rating scale. Insomnia, state of atopic dermatitis (Scoring Atopic Dermatitis; SCORAD), quality of life and therapy benefit were also assessed. No significant difference between active treatment and vehicle was found at any of the time-points for any of the investigated parameters. Under the experimental conditions of the study, sertaconazole 2% cream did not exert anti-pruritic effects that were better than vehicle in subjects with atopic dermatitis who had chronic pruritus. Trial registration ClinicalTrials.gov #NCT01792713

Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: Marker candidates for dementia with Lewy bodies

Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nonclemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of HFABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum HFABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio >= 8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB. Copyright (c) 2007 S. Karger AG, Basel

Granulocyte-Colony Stimulating Factor (G-CSF) Improves Motor Recovery in the Rat Impactor Model for Spinal Cord Injury

Granulocyte-colony stimulating factor (G-CSF) improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function

S2k guideline: Diagnosis and treatment of chronic pruritus

Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org

Th2/Th17 cell associated cytokines found in seroma fluids after breast cancer surgery

Purpose The development of a seroma after breast cancer surgery is a common postoperative complication seen after simple mastectomy and axillary surgery. We could recently demonstrate that breast cancer patients undergoing a simple mastectomy with subsequent seroma formation developed a T-helper cell increase within the aspirated fluid measured by flow cytometry. The same study revealed a Th2 and/or a Th17 immune response in peripheral blood and seroma fluid of the same patient. Based on these results and within the same study population, we now analyzed the Th2/Th17 cell associated cytokine content as well as the best known clinical important cytokine IL-6. Methods Multiplex cytokine measurements (IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22) were done on 34 seroma fluids (Sf) after fine needle aspiration of patients who developed a seroma after a simple mastectomy. Serum of the same patient (Sp) and that of healthy volunteers (Sc) were used as controls. Results We found the Sf to be highly cytokine rich. Almost all analyzed cytokines were significantly higher in abundance in the Sf compared to Sp and Sc, especially IL-6, which promotes Th17 differentiation as well as suppresses Th1 differentiation in favor of Th2 development. Conclusion Our Sf cytokine measurements reflect a local immune event. In contrast, former study results on T-helper cell populations in both Sf and Sp tend to demonstrate a systemic immune process

Synergy between multiple microtubule-generating pathways confers robustness to centrosome-driven mitotic spindle formation.

notes: PMCID: PMC3898610types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.The mitotic spindle is defined by its organized, bipolar mass of microtubules, which drive chromosome alignment and segregation. Although different cells have been shown to use different molecular pathways to generate the microtubules required for spindle formation, how these pathways are coordinated within a single cell is poorly understood. We have tested the limits within which the Drosophila embryonic spindle forms, disrupting the inherent temporal control that overlays mitotic microtubule generation, interfering with the molecular mechanism that generates new microtubules from preexisting ones, and disrupting the spatial relationship between microtubule nucleation and the usually dominant centrosome. Our work uncovers the possible routes to spindle formation in embryos and establishes the central role of Augmin in all microtubule-generating pathways. It also demonstrates that the contributions of each pathway to spindle formation are integrated, highlighting the remarkable flexibility with which cells can respond to perturbations that limit their capacity to generate microtubules.Biotechnology and Biological Sciences Research Council PhD studentship (to D.H.)Wellcome Trust Institutional Strategic Support Fund WT097835MF (to J.G.W. and J.M.)

Single-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors

Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we establish and characterize different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identify distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validate that MYC RT originate from these progenitor cells. We uncover an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impair tumor growth in vitro and in vivo. In summary, our work sheds light on the origin of RT and supports the clinical relevance of DNA methyltransferase inhibitors against this disease

Real-world clinical experience with Idebenone in the treatment of Leber hereditary optic neuropathy

Background: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. Methods: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. Results: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. Conclusions: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone