Beckmann Rearrangement of Cyclotriveratrylene (CTV) Oxime: Tandem Beckmann-Electrophilic Aromatic Addition

The Beckmann rearrangement has been performed on the oxime of cyclotriveratrylene (CTV) with thionyl chloride affording the ring-expanded 10-membered ring amide exclusively in high yield. Modified conditions afford a helical pentacycle derived from an unusual tandem Beckmann rearrangement and electrophilic aromatic addition followed by demethylation and tautomerization

Signaling between bacterial and fungal biocontrol agents in a strain mixture

The use of bacterial and fungal strain mixtures is a promising way to improve efficacy of biocontrol treatments. Certain Pseudomonas and Trichoderma strains belong to the most common studied biocontrol agents. One key factor for the biocontrol efficacy of several P. fluorescens strains is the synthesis of 2,4-diacetylphloroglucinol (DAPG). Production of chitinases, such as the ECH42 endochitinase and the NAG1 N-acetyl-β-d-glucosaminidase, is a primary mechanism of action for T. atroviride. We examined the molecular interactions between the DAPG-producing P. fluorescens strains CHA0 and Q2-87 and chitinase-producing T. atroviride P1. Interactions were monitored using the reporter gene constructs, phlA'-'lacZ translational fusion in P. fluorescens CHA0 and ech42-goxA or nag1-goxA fusions in T. atroviride P1. We found that DAPG enhanced nag1, but not ech42 expression, whereas an unidentified substance from P. fluorescens CHA0 repressed expression of both Trichoderma chitinases. Addition of T. atroviride P1 culture filtrates to growing cultures of P. fluorescens enhanced phlA expression transiently during growth. These results indicate that negative and positive effects on expression of key biocontrol genes may occur while mixing antagonist

Large-Scale Application of a Telephone-Based Test of Cognitive Functioning in Older Adults

Aims: The study of cognitive functioning in large epidemiological settings is hampered by a lack of instruments for the remote assessment of cognitive performance, especially when targeting variability across the full range of adult functioning. The present study examined the practicability of such investigations using a recently developed telephone interview (Cognitive Telephone Screening Instrument, COGTEL). Methods: A subcohort of an ongoing epidemiological study in the elderly German population (ESTHER) was interviewed via telephone by trained personnel. These data were combined with sociodemographic information obtained by standardized self-administered questionnaires, and analysed by tabulation, histograms and regression models. Results: A total of 1,697 interviews could be analysed. The eligible participants had a mean age ± standard deviation of 74.0 ± 2.8 years. The COGTEL total scores closely followed a normal distribution with no evidence of a ceiling effect. In adjusted regression models, COGTEL total and subcomponent scores were negatively associated with age and strongly positively with higher education, whereas the association with sex was less consistent. Conclusions: The results suggest that the COGTEL can readily be administered to large study populations and produces plausible and informative results. Education should be considered in all investigations using this instrument and requires further in-depth analyses. Future studies will need to elucidate its associations with risk factors and its prognostic potential for cognitive decline and dementia.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Combinations of low-frequency genetic variants might predispose to familial pancreatic cancer

Familial pancreatic cancer (FPC) is an established but rare inherited tumor syndrome that accounts for approximately 5% of pancreatic ductal adenocarcinoma (PDAC) cases. No major causative gene defect has yet been identified, but germline mutations in predisposition genes BRCA1/2, CDKN2A and PALB2 could be detected in 10–15% of analyzed families. Thus, the genetic basis of disease susceptibility in the majority of FPC families remains unknown. In an attempt to identify new candidate genes, we performed whole-genome sequencing on affected patients from 15 FPC families, without detecting BRCA1/2, CDKN2A or PALB2 mutations, using an Illumina based platform. Annotations from CADD, PolyPhen-2, SIFT, Mutation Taster and PROVEAN were used to assess the potential impact of a variant on the function of a gene. Variants that did not segregate with pancreatic disease in respective families were excluded. Potential predisposing candidate genes ATM, SUFU, DAB1, POLQ, FGFBP3, MAP3K3 and ACAD9 were identified in 7 of 15 families. All identified gene mutations segregated with pancreatic disease, but sometimes with incomplete penetrance. An analysis of up to 46 additional FPC families revealed that the identified gene mutations appeared to be unique in most cases, despite a potentially deleterious ACAD9 Ala326Thr germline variant, which occurred in 4 (8.7%) of 46 FPC families. Notably, affected PDAC patients within a family carried identical germline mutations in up to three different genes, e.g., DAB1, POLQ and FGFBP3. These results support the hypothesis that FPC is a highly heterogeneous polygenetic disease caused by low-frequency or rare variants

Lehrende lernen Lernberatung : Qualitativ-interaktionsanalytische Betrachtung einer Lernberatungssequenz zum Kursinhalt Autogenes Training im Rahmen eines Qualifizierungsprojekts für Kursleiter/innen

Im Kontext der Diskussion um selbstgesteuertes Lernen werden gegenüber der Erwachsenenbildung seit Beginn der 1990er Jahre umfassende Transformations- und Innovationsanforderungen auf unterschiedlichen Ebenen formuliert. Bezogen auf die Personengruppe der Kursleitenden verdichtet sich die Debatte in der Forderung nach einer mehr oder weniger radikalen Veränderung des professionellen Selbstverständnisses und reüssiert unter dem Begriff ‚Lernberatung’. Mit diesem Schlagwort, das seine Attraktivität u.a. auch aus seiner Funktion als begriffliche Schnittstelle zweier aktuell hochkonjunktureller Diskussionsbereiche innerhalb der Erwachsenenbildung (selbstgesteuertes Lernen und Beratung) bezieht, wird – wenn auch oft relativ unspezifisch – eine Abwendung vom Prinzip der linearen Wissensvermittlung mit dem Ziel der Ermöglichung, Begleitung und Unterstützung stärker selbstgesteuerter Lernprozesse gefasst. Dabei bleibt jedoch (neben vielem anderen, wie beispielsweise den Konsequenzen auf der organisationalen oder finanzierungstechnischen Ebene) nach wie vor unklar, welche konkreten Kompetenzen Lernberatende für ihr verändertes professionelles Handeln benötigen und wie diese zu erwerben sind. Hinzu kommt, dass Lernberatung auch konzeptionell bisher keineswegs einheitlich gefasst ist. Gleichwohl wird Lernberatung als veränderte Handlungs- und Interaktionsform – (nicht nur) in vielfältigen Forschungs- und Modellprojekten – bereits durchgeführt und ist damit unbestreitbar Teil, erwachsenenbildnerischer Realität. Doch was geschieht tatsächlich in diesen Lernberatungsprozessen? In welcher Weise nehmen Kursleitende ihre neue Rolle wahr? Wie etablieren sie eine Lernberatungssituation? Auf welche Verhaltensmuster, welches Vorwissen greifen sie zurück, um in einer neuen Tätigkeit Handlungssicherheit zu erlangen? Und: Wie verhalten sich die Teilnehmenden im Umgang mit dem neuen Element erwachsenenbildnerischer Praxis? Was erwarten sie von ihren Lernberater/innen? In welchen Situationen, mit welchen Zielsetzungen und Erwartungen nehmen sie Lernberatung wahr? Welche Schwierigkeiten tauchen dabei auf? Kurz: Wie gelingt es den Akteur/innen, der neuen Praxis durch ihre Handlungen Sinn zu geben? Und wie stellen sich Lernberatungen dann als Teil der erwachsenenbildnerischen Realität dar? Um sich dieser Frage zu nähern, wendet sich die vorliegende Arbeit dem Phänomen Lernberatung empirisch zu. Dafür wird eine Lernberatungssequenz, die in einem Kurs zum Thema Autogenes Training im Kontext eines Qualifizierungsprojekts für Kursleitende stattfand, ausgewertet. Die Analyse erfolgt dabei als qualitative Interaktionsanalyse, die sich dadurch auszeichnet, dass die zu erforschende Handlung in ihrer Sequenzialität, d.h. in ihrem tatsächlichen Interaktionsverlauf aufgegriffen und eng am Text Satz für Satz mikroanalytisch interpretiert wird. Als methodologische Orientierungspunkte werden hierfür sowohl die (ethnomethodologische) Konversationsanalyse als auch die Objektive Hermeneutik herangezogen. Die empirische Analyse wird dabei gerahmt von einem theoretisch orientierten Teil, in dem die Debatte um selbstgesteuertes Lernen historisch, begrifflich und hinsichtlich der verwendeten Begründungsebenen aufgearbeitet wird (Kapitel 2) und unterschiedliche Konzepte zur Lernberatung referiert werden (Kapitel 3), sowie von einer forschungsgeschichtlich-methodologischen Einordnung, in der neben einem Exkurs zur Geschichte empirischer Forschungen in der Erwachsenenbildung die gewählte Analyseform der Sequenzanalyse sowohl hinsichtlich ihrer theoretischen und methodologischen Bezüge als auch anhand der Darstellung exemplarischer Studien umfassend dargestellt wird. Als eine zentrale Erkenntnis der empirischen Analyse lässt sich formulieren, dass Lernberatungshandeln in der Praxis offensichtlich nicht ausschließlich – wie in der Literatur häufig beschrieben – vom Handlungsschema der Lehre abzugrenzen ist, sondern – gerade im Bereich körper- und gesundheitsbezogener Angebote – die Grenze zum (quasi-)therapeutischen Gespräch schnell überschritten werden kann. Die Mikroanalyse kann dabei aufzeigen, wie sich dies im Gespräch im Einzelnen vollzieht, wie die Bedeutung im Gesprächsverlauf zwischen den Beteiligten interaktiv ausgehandelt wird und wie sie ihre Erwartungen, Rollenvorstellungen und Selbstbilder dabei in die gemeinsame Situation einbringen.Within the debate surrounding the increasingly discussed role of self-directed learning in continuing adult education, one repeatedly finds the demand for a shift in the professional conduct of overseeing learning from traditional approaches to a facilitated learning environment. This thesis illustrates relevant theoretical background and empirically deals with the question, how such learning consultation take place in adult education practice. Which expectations do the participants themselves introduce to situations and how do they negotiate expectations and interpretations in the course of interaction? For this thesis an analytical assessment of a learning consultation situation within an autogenous training seminar was conducted. As one main result can be asserted that the learning consultation in practice obviously is not only reliant upon action schemes for teaching but also relies to some degree upon almost therapeutic-type consultations that can quickly go beyond the boundaries of ordinary learning environments

Digital research data: from analysis of existing standards to a scientific foundation for a modular metadata schema in nanosafety

Background: Assessing the safety of engineered nanomaterials (ENMs) is an interdisciplinary and complex process producing huge amounts of information and data. To make such data and metadata reusable for researchers, manufacturers, and regulatory authorities, there is an urgent need to record and provide this information in a structured, harmonized, and digitized way. Results: This study aimed to identify appropriate description standards and quality criteria for the special use in nanosafety. There are many existing standards and guidelines designed for collecting data and metadata, ranging from regulatory guidelines to specific databases. Most of them are incomplete or not specifically designed for ENM research. However, by merging the content of several existing standards and guidelines, a basic catalogue of descriptive information and quality criteria was generated. In an iterative process, our interdisciplinary team identified deficits and added missing information into a comprehensive schema. Subsequently, this overview was externally evaluated by a panel of experts during a workshop. This whole process resulted in a minimum information table (MIT), specifying necessary minimum information to be provided along with experimental results on effects of ENMs in the biological context in a flexible and modular manner. The MIT is divided into six modules: general information, material information, biological model information, exposure information, endpoint read out information and analysis and statistics. These modules are further partitioned into module subdivisions serving to include more detailed information. A comparison with existing ontologies, which also aim to electronically collect data and metadata on nanosafety studies, showed that the newly developed MIT exhibits a higher level of detail compared to those existing schemas, making it more usable to prevent gaps in the communication of information. Conclusion: Implementing the requirements of the MIT into e.g., electronic lab notebooks (ELNs) would make the collection of all necessary data and metadata a daily routine and thereby would improve the reproducibility and reusability of experiments. Furthermore, this approach is particularly beneficial regarding the rapidly expanding developments and applications of novel non-animal alternative testing methods

Organic matter characteristics of a rapidly eroding permafrost cliff in NE Siberia (Lena Delta, Laptev Sea region)

Organic carbon (OC) stored in Arctic permafrost represents one of Earth’s largest and most vulnerable terrestrial carbon pools. Amplified climate warming across the Arctic results in widespread permafrost thaw. Permafrost deposits exposed at river cliffs and coasts are particularly susceptible to thawing processes. Accelerating erosion of terrestrial permafrost along shorelines leads to increased transfer of organic matter (OM) to nearshore waters. However, the amount of terrestrial permafrost carbon and nitrogen as well as the OM quality in these deposits is still poorly quantified. We define the OM quality as the intrinsic potential for further transformation, decomposition and mineralisation. Here, we characterise the sources and the quality of OM supplied to the Lena River at a rapidly eroding permafrost river shoreline cliff in the eastern part of the delta (Sobo-Sise Island). Our multi-proxy approach captures bulk elemental, molecular geochemical and carbon isotopic analyses of Late Pleistocene Yedoma permafrost and Holocene cover deposits, discontinuously spanning the last ~52 kyr. We showed that the ancient permafrost exposed in the Sobo-Sise cliff has a high organic carbon content (mean of about 5 wt %). The oldest sediments stem from Marine Isotope Stage (MIS) 3 interstadial deposits (dated to 52 to 28 cal ka BP) and are overlaid by last glacial MIS 2 (dated to 28 to 15 cal ka BP) and Holocene MIS 1 (dated to 7–0 cal ka BP) deposits. The relatively high average chain length (ACL) index of n-alkanes along the cliff profile indicates a predominant contribution of vascular plants to the OM composition. The elevated ratio of iso and anteiso-branched fatty acids (FAs) relative to mid- and long-chain (C�20) n-FAs in the interstadial MIS 3 and the interglacial MIS 1 deposits suggests stronger microbial activity and consequently higher input of bacterial biomass during these climatically warmer periods. The overall high carbon preference index (CPI) and higher plant fatty acid (HPFA) values as well as high C=N ratios point to a good quality of the preserved OM and thus to a high potential of the OM for decomposition upon thaw. A decrease in HPFA values downwards along the profile probably indicates stronger OM decomposition in the oldest (MIS 3) deposits of the cliff. The characterisation of OM from eroding permafrost leads to a better assessment of the greenhouse gas potential of the OC released into river and nearshore waters in the future

Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood

Background: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in children is scarce. Methods: Six children with genetically proven HPS-2 presented to the chILD-EU register between 2009 and 2017; the data were collected systematically and imaging studies were scored blinded. Results: Pulmonary symptoms including dyspnea, coughing, need for oxygen, and clubbing started 3.3 years before the diagnosis was made at the mean age of 8.83 years (range 2-15). All children had recurrent pulmonary infections, 3 had a spontaneous pneumothorax, and 4 developed scoliosis. The frequency of pulmonary complaints increased over time. The leading radiographic pattern was ground-glass opacities with a rapid increase in reticular pattern and traction bronchiectasis between initial and follow-up Computer tomography (CT) in all subjects. Honeycombing and cysts were newly detectable in 3 patients. Half of the patients received a lung biopsy for diagnosis; histological patterns were cellular non-specific interstitial pneumonia, usual interstitial pneumonia-like, and desquamative interstitial pneumonia. Conclusions: HPS-2 is characterized by a rapidly fibrosing lung disease during early childhood. Effective treatments are required

Evaluating Depressive Symptoms in Schizophrenia: A Psychometric Comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale

Background: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. Sampling and Methods: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. Results: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS sub-scores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. Conclusions:The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients. Copyright (c) 2012 S. Karger AG, Base