Dissemination strategies of the entomopathogenic fungus Lecanicillium muscarium (Petch.) Zare, Gams syn. Verticillium lecanii in populations of the western flower thrips Frankliniella occidentalis (Pergande 1895)

Die Wirksamkeit des entomopathogenen Pilzes (EPP) L. muscarium im Einsatz gegen F. occidentalis ist in unseren Versuchen mehrfach belegt worden. In verschiedenen Schalen-, Käfig- und Gewächshausuntersuchungen wurde festgestellt, dass die Applikation der Sporensuspension in das Wirtshabitat zur Infektion und zum Absterben der Wirte führt. Dabei konnte auch die saprophytische Entwicklung des Pilzes als Mycel mit Sporulation auf den Kadavern beobachtet werden (Hetsch 2004, Lerche et al. 2004, 2005). Ausgehend von den sporulierenden Kadavern sind die Disseminationsstrategien in der Wirt-Parasit-Beziehung F. occidentalis und L. muscarium, in Relation zum Verhalten des Wirtes sowie der physikalischen Faktoren Wasser und Luftbewegung, untersucht worden. Die Aufklärung dieser Zusammenhänge ist entscheidend für eine höhere Effizienz und Nachhaltigkeit des Pilzes im Praxiseinsatz.The entomopathogenic fungus L. muscarium can be used to control populations of the western flower thrips F. occidentalis. In laboratory, semi-field and greenhouse trials the infection and mortality of the host population were recorded. Secondarily the fungus grew and sporulated on the cadavers of F. occidentalis. Now trials were conducted to describe the dissemination strategies of L. muscarium in this host-pathogen-relationship. The results show different possibilities of pathogen dispersal. One of the most important ways of dissemination is by the behaviour and movement of the hosts. The dispersal was horizontally within the population, in and between the generations. The second way of pathogen dispersal by the host was the contamination of the insect’s habitat. This included the growth of the fungus after death of the host, the sporulation of infectious stages in cast exuviae after moulting and by the loss of spores during the movement of the host. The physical agent running water also dispersed the pathogen efficient within the host habitat. The results were discussed

Investigation of the distribution of Strauzia longipennis Wied. in Berlin and in the Federal Land Brandenburg

Außerhalb Nordamerikas wurde die dort endemische Sonnenblumenfruchtfliege Strauzia longipennis Wied. erstmals 2009/10 durch Sichtungen und Fänge in Berlin dokumentiert. Da die Adaption dieser Fruchtfliege an gemäßigte Klimate den Verdacht nahelegte, dass eine Überwinterung in unseren Breiten möglich ist und darüber hinaus die Art als Quarantäneschädling geführt wird, fanden im Jahr 2011 umfangreiche systematische Erhebungen zur Verbreitung dieser Art in Berlin und im Bundesland Brandenburg an Sonnenblumen Helianthus annuus L. und Topinambur H. tuberosus L. statt. Es wurden Pflanzen sowohl von Feldern mit erwerbsmäßigem Anbau von H. annuus als auch von Feldern mit Durchwuchs, von Feldrändern, aus einer Gärtnerei, von Versuchsflächen und aus dem Bereich von Haus- und Kleingärten auf den Befall mit S. longi­pennis untersucht. Dieses Monitoring wurde 2012 als Übersichtsbonitur weitergeführt. Im Jahr 2011 wurden im Land Brandenburg insgesamt 27 Fundorte festgestellt, wobei es sich hauptsächlich um Schläge mit feldmäßigem Anbau von H. annuus handelte. Nur in den Landkreisen Oberspreewald-Lausitz und Prignitz konnte der Schädling nicht beobachtet werden. In Berlin wurden 16 Fundorte nach­gewiesen. Im Jahr 2012 sank die Zahl der in Brandenburg positiv bonitierten Orte auf zwei; hier war nur ein geringer Befall zu verzeichnen. An zwei Standorten in Berlin wurde S. longipennis jedoch mit hoher Abundanz nachgewiesen. Die Ergebnisse der beiden Boniturjahre belegen, dass die Sonnenblumenfruchtfliege in Berlin und im Land Brandenburg territorial bereits weit verbreitet ist, aber deutlichen Abundanzschwankungen unterliegt. Das wiederholte Auftreten der Art auf Flächen in Berlin und im Land Brandenburg im Jahr 2012 beweist, dass sich die Art in der Region dauerhaft etabliert hat. Zusätzlich belegen die Ergebnisse, dass die Einschleppung in Deutschland bereits deutlich früher als 2009/10 – bei der ersten Registrierung in Berlin – stattgefunden haben muss. Darüber hinaus zeigten die Untersuchungen, dass Topinambur ebenfalls zum Wirtspflanzenspektrum der Fruchtfliege in Deutschland gehört. Das Auftreten der Art in Berlin und im Land Brandenburg über mehrere Jahre und der Mangel an Wissen über die eingeschleppte Population macht weitere Forschung zu verschiedenen Aspekten dringend notwendig.    The sunflower maggot Strauzia longipennis Wied. is endemic in North America. First observations on the fruit fly in Europe were obtained in Berlin and dates back to 2009/10. Considering the adaption of the species to climatic conditions in Central Europe and the status as quarantine pest an extensive survey on the occurrence of the fruit fly was carried out in Berlin and Federal Land Brandenburg in 2011. The infestation with S. longipennis was investigated on sunflower H. annuus as well as Jerusalem artichoke H. tuberosus L. Therefore, plants were examined growing on fields i.e. sunflower fields and other crops (plants growing through or growing on the edges) as well as plants from a nursery, from experimental fields, backyards, allotments and roadsides. Further monitoring was conducted in 2012 in Land Brandenburg to achieve an overview of the situation of infestation, whereas in Berlin, two sides were closely examined. In 2011 S. longipennis was found in Land Brandenburg and Berlin. In Brandenburg, on 27 locations mostly cultivated with Helianthus annuus L. were plants registered to be infested with the fruit fly. Only in districts Oberspreewald-Lausitz and Prigniz, the sunflower maggot could not be detected. In Berlin infested plants were observed at 16 locations. One year later, the number of positively tested fields in Brandenburg declined. The sunflower maggot could be detected only on two fields. Furthermore, abundance on these fields was low. Nevertheless, relatively high abundance of the species was observed at two locations in Berlin. The results of both years verify the territorial wide distribution of the sunflower maggot within Berlin and the Federal Land Brandenburg. Further, significant variations of abundance between the years were shown. Despite the differences in the years, the repeated presence of S. longipennis in Berlin and Land Brandenburg proves the permanent establishment of the species within the region. Additionally, it can be assumed that the introduction of the species in Germany must have taken place quite earlier than with the first detection in Berlin in 2009/10. Furthermore, the study demonstrates the Jerusalem artichoke H. tuberosus as another host plant of the fly species within Germany. The occurence of S. longipennis in Berlin and Land Brandenburg for several years and the lack of knowledge regarding the introduced population emphasize the need for further research.   &nbsp

The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus

BACKGROUND: The increase in antibiotic resistant bacteria has led to renewed interest in development of alternative antimicrobial compounds such as antimicrobial peptides (AMPs), either naturally-occurring or synthetically-derived. Knowledge of the mode of action (MOA) of synthetic compounds mimicking the function of AMPs is highly valuable both when developing new types of antimicrobials and when predicting resistance development. Despite many functional studies of AMPs, only a few of the synthetic peptides have been studied in detail. RESULTS: We investigated the MOA of the lysine-peptoid hybrid, LP5, which previously has been shown to display antimicrobial activity against Staphylococcus aureus. At concentrations of LP5 above the minimal inhibitory concentration (MIC), the peptoid caused ATP leakage from bacterial cells. However, at concentrations close to the MIC, LP5 inhibited the growth of S. aureus without ATP leakage. Instead, LP5 bound DNA and inhibited macromolecular synthesis. The binding to DNA also led to inhibition of DNA gyrase and topoisomerase IV and caused induction of the SOS response. CONCLUSIONS: Our data demonstrate that LP5 may have a dual mode of action against S. aureus. At MIC concentrations, LP5 binds DNA and inhibits macromolecular synthesis and growth, whereas at concentrations above the MIC, LP5 targets the bacterial membrane leading to disruption of the membrane. These results add new information about the MOA of a new synthetic AMP and aid in the future design of synthetic peptides with increased therapeutic potential

Alles im grünen Bereich!

ALLES IM GRÜNEN BEREICH! Alles im grünen Bereich! / Miller, Leif (Rights reserved) ( -

Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect

Anoctamins are a family of Ca$^{2+}$-activated proteins that may act as ion channels and/or phospholipid scramblases with limited understanding of function and disease association. Here, we identified five de novo and two inherited missense variants in ANO4 (alias TMEM16D) as a cause of fever-sensitive developmental and epileptic or epileptic encephalopathy (DEE/EE) and generalized epilepsy with febrile seizures plus (GEFS+) or temporal lobe epilepsy. In silico modeling of the ANO4 structure predicted that all identified variants lead to destabilization of the ANO4 structure. Four variants are localized close to the Ca$^{2+}$ binding sites of ANO4, suggesting impaired protein function. Variant mapping to the protein topology suggests a preliminary genotype-phenotype correlation. Moreover, the observation of a heterozygous ANO4 deletion in a healthy individual suggests a dysfunctional protein as disease mechanism rather than haploinsufficiency. To test this hypothesis, we examined mutant ANO4 functional properties in a heterologous expression system by patchclamp recordings, immunocytochemistry, and surface expression of annexin A5 as a measure of phosphatidylserine scramblase activity. All ANO4 variants showed severe loss of ion channel function and DEE/EE associated variants presented mild loss of surface expression due to impaired plasma membrane trafficking. Increased levels of Ca$^{2+}$-independent annexin A5 at the cell surface suggested an increased apoptosis rate in DEE-mutant expressing cells, but no changes in Ca$^{2+}$-dependent scramblase activity were observed. Co-transfection with ANO4 wild-type suggested a dominant-negative effect. In summary, we expand the genetic base for both encephalopathic sporadic and inherited fever-sensitive epilepsies and link germline variants in ANO4 to a hereditary disease

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges