Biosynthesis of the Cytochalasans. The Mode of Incorporation of L-Methionine into the Cytochalasins A and B, Protophomin and Proxiphomin

Incorporation of [l3C,2H3-CHs]-L-methionine into cytochala-: sin A (I), cytochalasin B (II), proxiphomin (III) and protophomin (IV) by Phoma exiqua var. exiqua demonstrated that the two C-methylations occur with retention of all three H-atoms of the methyl group. Conclusions are drawn concerning the stage of the methylation reaction during the biogenetic pathway. On the basis of the results amore detailed general scheme of the cytochalasan biogenesis is propose

Soil biological quality in short- and long-term field trials with conventional and organic fertility input types

Soils of the DOK trial and three other field trials with manure input were analysed for effects on soil biology. While long-term effects indicate a new steady state at the DOK trial site, differences at the other field trials suggest that fresh manure at the Bonn trial and chicken manure at the UK sites are at least temporarily advantageous, probably due to their relatively fast mineralization

Erfahrungen mit RIMpro in Versuch und Praxis

Die Saison 2005 war ein ausgesprochen anspruchsvolles Jahr für die Bekämpfung von Schorf. In der Primärsaison wurden an 41 Tagen Ascosporenausstoss beobachtet, davon an 20 Tagen Ausstösse mit grösseren Mengen von Ascosporen. Gemäss Modellrechnungen nach RIMpro kam es dadurch zu 8 Ereignissen mit ernstzunehmendem Infektionsrisiko. Zum Vergleich: im Jahr 2004 wurden nur gerade 2-3 derartige Ereignisse verzeichnet. Der Vergleich des gemessenen Ascosporenausstosses mit den Modellrechnungen von RIMpro zeigt, dass die Modellrechnungen relativ gut mit der Realität übereinstimmen. Unsere Erfahrungen im Jahr 2005 zeigen aber, dass für die Kalibrierung des Modells Ascosporenzählungen zu Beginn der Saison unerlässlich sind. Nur wenn die ersten Austösse erfasst werden, können verlässliche Prognosen in der nachfolgenden Saison gerechnet werden. Aufgrund dieser Erfahrung werden wir weiterhin eine Sporenfalle am Standort Frick betreiben und in der Romandie nach Möglichkeit lokale Zählungen einbeziehen. Die Dienstleistung Schorfwarnung mit RIMpro und online Beratung, die wir seit 2004 anbieten (www.fibl.org/forschung/pflanzenschutz-krankheiten/schorfprognose/index.php), wird zunehmend von Produzenten als Entscheidungshilfe genutzt. Die 4 Referenzstationen stehen im Wallis, der Waadt, Frick und der Ostschweiz und werden während der Saison alle 2 Stunden aktualisiert, sodass topaktuelle Informationen zur Verfügung stehen. Die Daten und Informationen der Referenzstandorte sind als Anhaltspunkte für die Praxis gedacht. Die Interpretation der Informationen und den Bezug auf die eigene lokale Situation muss aber jeder Produzent selbst vornehmen

Personen, die nicht am Erwerbsleben teilnehmen - Analyse sozioökonomischer Merkmale unter besonderer Berücksichtigung des Haushaltskontextes und Bestimmung des Arbeitskräftepotenzials : Endbericht

Für die Fachkräftesicherung stellen bisher nicht am Arbeitsmarkt aktive Personen (sog. Nichterwerbspersonen) ein wichtiges Potenzial dar. Die vorliegende Studie untersucht die Eigenschaften dieser Personengruppe und schätzt auf dieser Grundlage ihr Aktivierungspotenzial ein. Betrachtet werden Aspekte wie sozio-demographische Merkmale von Nichterwerbspersonen, Übergänge in und aus Nichterwerbstätigkeit, Faktoren, die einen Austritt aus Nichterwerbstätigkeit fördern oder hemmen sowie Erwerbspläne von Nichterwerbspersonen. Mit Hilfe von Clusteranalysen werden Typen von Nichterwerbstätigen identifiziert, die die Grundlage für die Abschätzung von Wahrscheinlichkeiten zur Aktivierung bilden. Abschließend werden Aktivierungsmaßnahmen diskutiert

Psychographische Verortung von Menschen mit Diabetes: Auswirkungen auf die Produktgestaltung und Kommunikation

Für den Erfolg eines Produktes oder einer Dienstleistung ist die umfassende Kenntnis der Bedürfnisse, Wahrnehmungs- und Entscheidungsfilter von Zielgruppen entscheidend. Nur eine zielgerichtete, zur Zielgruppe passende Produktentwicklung und -vermarktung kann Auf Dauer erfolgreich sein. Da soziodemographische Zielgruppendefinitionen heute alleine nicht valide genug sind, um Zielgruppen umfassend zu verstehen, werden im Marketing zu-nehmend psychographische Verortungen von Zielgruppen verwendet. Auch bei chronisch Kranken reichen rein soziodemographische und medizinische Kriterien nicht aus, um Produkte und Dienstleistungen passend zu gestalten. Psychographische Erkenntnisse können die klassischen Kriterien sinnvoll ergänzen. Am Beispiel von Menschen mit Diabetes wird in einer internationalen empirischen Studie gezeigt, dass sich Menschen mit Diabetes mit Hilfe eines neuropsychologisch fundierten, visuellen Testverfahrens (dem u.a. an der NORD-AKADEMIE entwickelten Visual Questionnaire, ViQ) eindeutig psychographisch verorten lassen. Die Implikationen und Anwendungsmöglichkeiten dieser psychographischen Erkenntnisse für die Produktentwicklung, Kommunikation, Vertrieb und Marketing bei Krankenkassen, medizinischem Personal und der Pharmabranche werden aufgezeigt und kritisch diskutiert. --

The Database of Cross-Linguistic Colexifications, reproducible analysis of cross-linguistic polysemies

Advances in computer-assisted linguistic research have been greatly infuential in reshaping linguistic research. With the increasing availability of interconnected datasets created and curated by researchers, more and more interwoven questions can now be investigated. Such advances, however, are bringing high requirements in terms of rigorousness for preparing and curating datasets. Here we present CLICS, a Database of Cross-Linguistic Colexifcations (CLICS). CLICS tackles interconnected interdisciplinary research questions about the colexifcation of words across semantic categories in the world's languages, and show-cases best practices for preparing data for cross-linguistic research. This is done by addressing shortcomings of an earlier version of the database, CLICS2, and by supplying an updated version with CLICS3, which massively increases the size and scope of the project. We provide tools and guidelines for this purpose and discuss insights resulting from organizing student tasks for database updatesTT, MSW, NES, YL, and JML were funded by the the ERC Starting Grant 715618 Computer-Assisted Language Comparison (http://calc.digling.org). SJG was supported by the Australian Research Council’s Discovery Projects funding scheme (project number DE 120101954) and the ARC Center of Excellence for the Dynamics of Language grant (CE140100041). MKT was supported by the Riksbankens Jubileums Fond (Grant SAB17-0588:1). TB was funded by the Swiss National Science Foundation, P2BEP1_181779, “Reconstruction of Proto-Western Kho-Bwa”

Stretching and challenging the boundaries of law: varieties of knowledge in biotechnologies regulation

The paper addresses the question of adaptation of existing regulatory frameworks in the face of innovation in biotechnologies, and specifically the roles played in this by various expert knowledge practices. We identify two overlapping ideal types of adaptation: first, the stretching and maintenance of a pre-existing legal framework, and second, a breaking of existing classifications and establishment of a novel regime. We approach this issue by focusing on varieties of regulatory knowledge which, contributing to and parting of political legitimacy, in principle enable the making of legally binding decisions about risks and benefits of technologies. We base the discussion around two case studies, one of animal biotechnology ethical regulation, the other of ‘advanced therapy’ medicinal product regulation, both in the context of European Union frameworks. Specifically, we explore the knowledge configurations constituting expert committees and other institutional formations of expert regulatory knowledge in their political context. We show that where sectoral and moral boundaries are challenged, different modes of regulatory knowledge beyond scientific forms – legal, procedural, moral, economic and industrial – can shape regulatory innovations either by maintenance of regimes through commensuration and stretching, or through differentiation and separation creating new frameworks. We conclude that establishing an essential techno-scientific difference between pre-existing and novel technologies does not in itself require new regulatory structures, and that the regulatory strategy that is followed will be determined by a combination of different forms of knowledge

Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency

BACKGROUND: Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. OBJECTIVE: We explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance. METHODS: Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type vs. mutant LIG4 were performed in LIG4 knock-out Jurkat T cells and DNA damage tolerance was subsequently assessed. RESULTS: A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naïve CD4$^{+}$ T cells and low TCR-Vα7.2$^{+}$ T cells, while T/B-cell receptor repertoires showed only mild alterations. Cohort screening identified two other non-related patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T cell-intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient. CONCLUSION: We provide evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes