Fluoreszierende Metaboliten im Tryptophanstoffwechsel von M. furfur

M. furfur synthetisiert tryptophanabhängig ein braunes Pigment („Rohextrakt“), das aus einer Vielzahl von Pigmenten und Fluorochromen besteht. Zur näheren Charakterisierung der fluoreszierenden Substanzen wurde M. furfur 14 Tage auf einem tryptophanhaltigen Medium bei 32° C inkubiert und das gebildete Pigment aus dem Nährboden extrahiert. Der Rohextrakt wurde über Säulenchromatographie, Dünnschichtchromatographie und HPLC aufgereinigt. Es konnte ein erstes Fluorochrom isoliert und über Massenspektroskopie strukturell aufgeklärt werden. Pityrialacton (C20H12N2O3) ist eine in der Natur bisher nicht beschriebene Substanz. Es besteht aus zwei über einen Fünfring mit einer Lactoneinheit verbundenen Indolgruppen und fluoresziert in Lösung gelbgrün. Interessanterweise hat Pityrialacton im Fluoreszenzspektrum in wässriger Lösung ein Anregungsmaximum von 366 nm. Die gelbgrün fluoreszierende Substanz stellt damit einen Erklärungsansatz für die Fluoreszenzerscheinungen der Pityriasis versicolor im Wood-Licht (366 nm) dar. Dabei könnten sich die in der Literatur beschriebenen Farbunterschiede der fluoreszierenden Hautläsionen entsprechend den Farbvariationen des Pityrialacton in wässrigem (gelblich) oder lipophilerem Milieu (bläulich) aus einem individuell unterschiedlichen Hautmilieu (abhängig von der Schweiß- bzw. Talgproduktion) ergeben. Weiterhin kann durch die Bildung von UV-schützenden Substanzen die verminderte Sonnenbrandneigung in den depigmentierten Arealen bei der Pityriasis versicolor alba erklärt werden. Die Beteiligung der fluoreszierenden Bestandteile des Rohextraktes an dieser Wirkung konnte in einem Hefemodell nachgewiesen werden und findet im Charakter der Fluoreszenz, nämlich der Abgabe von absorbierter Energie in Form von Licht mit einem kleinen Wärmeanteil ihr Korrelat. Ferner sind auch andere nicht fluoreszierende Substanzen wie das Pityriacitrin an der Lichtschutzwirkung beteiligt. Außer dem gelbgrün fluoreszierenden Pityrialacton konnte orangefarbene Pityriaanhydrid (C20H12N2O3) aus dem Rohextrakt isoliert werden. Pityriaanhydrid imponiert rot-orange und ist ein Strukturisomer von Pityrialacton. Auch Pityriaanhydrid wurde bisher nicht als Naturstoff beschrieben, tritt aber als Zwischenstufe bei der Synthese von einer Gruppe von Proteinkinase C-Inhibitoren, den Bisindolylmaleimiden, auf. Durch die Identifizierung der ersten Substanzen aus dem Rohextrakt konnten Erklärungsansätze für verschiedene klinische Phänomene der Pityriasis versicolor geschaffen werden. Weitere Untersuchungen könnten dazu beitragen, neue Erkenntnisse über Stoffwechselprozesse bei M. furfur und die Pathogenese der Pityriasis versicolor zu gewinnen.With tryptophane as the main nitrogen source M. furfur produces a brownish pigment (“crude extract”), that consists of many pigments and fluorochromes. For investigation of the fluorochromes, M. furfur was incubated for 14 days at 32° C on a pigment-inducing medium and the pigment was extracted from the agar. The crude extract was purified by means of column chromatography, thin-layer chromatography and HPLC. A fluorochrome could be isolated and the structure of the pure metabolite was determined by mass spectrometry. Pityrialactone (C20H12N2O3) is a compound hitherto unknown in nature. It is a bisindolyl compound with a furan-2,3-dione structure which shows green-yellow fluorescence in solution. The green-yellow fluorescence of pityrialactone can explain the hitherto unelucidated fluorescence phenomena in pityriasis versicolor. Interestingly, excitation maxima of pityrialacton dissolved in water (366 nm) are exactly within the Wood’s lamp emission range. According to the different colours from pityrialactone in a watery or in a lipophilic milieu, the different colours of the skin lesions in pityriasis versicolor could result from a varying skin environment (dependent on the production of sweat and sebum). The production of UV-protective agents could explain the decreased sunburn risk in the depigmented areas in pityriasis versicolor alba. The protective properties of the fluorescing substances could be shown in a yeast model. During fluorescence, a large part of absorbed light energy is emitted as photon, only a small part is converted to heat. Thus, fluorochromes provide a reasonable mechanism to limit cellular damage by UV exposure. It appears that other non-fluorescing metabolites as the pityriacitrin also have UV-protective properties. Apart from the fluorescing pityrialactone, the isomeric pityriaanhydrid (C20H12N2O3) was isolated from the crude extract. Pityriaanhydrid has a red-orange colour. It has also not been described as a natural product but is an intermediate in the synthesis of a group of proteinkinase-C-inhibitors, the bisindolylmaleimids. The identification of the first compounds of the crude extract could explain different clinical phenomena in pityriasis versicolor. Further investigations could elucidate metabolic processes of M. furfur and pathogenesis of pityriasis versicolor

Controlled ecological evaluation of an implemented exercise-training programme to prevent lower limb injuries in sport: Population-level trends in hospital-treated injuries

Objective: Exercise-training programmes have reduced lower limb injuries in trials, but their population-level effectiveness has not been reported in implementation trials. This study aimed to demonstrate that routinely collected hospital data can be used to evaluate population-level programme effectiveness. Method: A controlled ecological design was used to evaluate the effect of FootyFirst, an exercise-training programme, on the number of hospital-treated lower limb injuries sustained by males aged 16–50 years while participating in community-level Australian Football. FootyFirst was implemented with ‘support’ (FootyFirst+S) or ‘without support’ (FootyFirst+NS) in different geographic regions of Victoria, Australia: 22 clubs in region 1: FootyFirst+S in 2012/2013; 25 clubs in region 2: FootyFirst+NS in 2012/2013; 31 clubs region 3: control in 2012, FootyFirst+S in 2013. Interrupted time-series analysis compared injury counts across regions and against trends in the rest of Victoria. Results: After 1 year of FootyFirst+S, there was a non-statistically significant decline in the number of lower limb injuries in region 1 (2012) and region 3 (2013); this was not maintained after 2 years in region 1. Compared with before FootyFirst in 2006–2011, injury count changes at the end of 2013 were: region 1: 20.0% reduction (after 2 years support); region 2: 21.5% increase (after 2 years without support); region 3: 21.8% increase (after first year no programme, second year programme with support); rest of Victoria: 12.6% increase. Conclusion: Ecological analyses using routinely collected hospital data show promise as the basis of population-level programme evaluation. The implementation and sustainability of sports injury prevention programmes at the population-level remains challenging

A maximum rupture model for the central and southern Cascadia subduction zone—reassessing ages for coastal evidence of megathrust earthquakes and tsunamis

A new history of great earthquakes (and their tsunamis) for the central and southern Cascadia subduction zone shows more frequent (17 in the past 6700 yr) megathrust ruptures than previous coastal chronologies. The history is based on along-strike correlations of Bayesian age models derived from evaluation of 554 radiocarbon ages that date earthquake evidence at 14 coastal sites. We reconstruct a history that accounts for all dated stratigraphic evidence with the fewest possible ruptures by evaluating the sequence of age models for earthquake or tsunami contacts at each site, comparing the degree of temporal overlap of correlated site age models, considering evidence for closely spaced earthquakes at four sites, and hypothesizing only maximum-length megathrust ruptures. For the past 6700 yr, recurrence for all earthquakes is 370–420 yr. But correlations suggest that ruptures at ∼1.5 ka and ∼1.1 ka were of limited extent (<400 km). If so, post-3-ka recurrence for ruptures extending throughout central and southern Cascadia is 510–540 yr. But the range in the times between earthquakes is large: two instances may be ∼50 yr, whereas the longest are ∼550 and ∼850 yr. The closely spaced ruptures about 1.6 ka may illustrate a pattern common at subduction zones of a long gap ending with a great earthquake rupturing much of the subduction zone, shortly followed by a rupture of more limited extent. The ruptures of limited extent support the continued inclusion of magnitude-8 earthquakes, with longer ruptures near magnitude 9, in assessments of seismic hazard in the region

Geodiversity assessment of Paraná state (Brazil): an innovative approach

Geodiversity is considered as the natural range of geological, geomorphological, and soil features, including their assemblages, relationships, properties, interpretations, and systems. A method developed for the quantitative assessment of geodiversity was applied to Parana ́ , a Brazilian state with an area of about 200,000 km2. The method is based on the overlay of a grid over different maps at scales ranging from 1/500,000 to 1/650,000, with the final Geodiversity Index the sum of five partial indexes calculated on a 25 9 25 km grid. The partial indexes represent the main components of geodi- versity, including geology (stratigraphy and lithology), geomorphology, paleontology, and soils. The fifth partial index covers mineral occurrences of geodiversity, such precious stones and metals, energy and industrial minerals, mineral waters, and springs. The Geodiversity Index takes the form of an isoline map that can be used as a tool in land-use planning, particularly in identifying priority areas for conservation, management, and use of natural resources at the state level.The Portuguese authors express their gratitude for the financial support given by the Fundacao para a Ciencia e a Tecnologia to the Centro de Geologia da Universidade do Porto, which partially supports this research. The Brazilian author expresses his gratitude for the financial support given by the CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) (Process Number 200074/2011-3)

Evolution of Exon-Intron Structure and Alternative Splicing

Despite significant advances in high-throughput DNA sequencing, many important species remain understudied at the genome level. In this study we addressed a question of what can be predicted about the genome-wide characteristics of less studied species, based on the genomic data from completely sequenced species. Using NCBI databases we performed a comparative genome-wide analysis of such characteristics as alternative splicing, number of genes, gene products and exons in 36 completely sequenced model species. We created statistical regression models to fit these data and applied them to loblolly pine (Pinus taeda L.), an example of an important species whose genome has not been completely sequenced yet. Using these models, the genome-wide characteristics, such as total number of genes and exons, can be roughly predicted based on parameters estimated from available limited genomic data, e.g. exon length and exon/gene ratio

Early Geometrical Thinking in the Environment of Patterns, Mosaics and Isometries

This book discusses the learning and teaching of geometry, with a special focus on kindergarten and primary education. It examines important new trends and developments in research and practice, and emphasizes theoretical, empirical and developmental issues. Further, it discusses various topics, including curriculum studies and implementation, spatial abilities and geometric reasoning, as well as the psychological roots of geometrical thinking and teacher preparation in geometry education. It considers these issues from historical, epistemological, cognitive semiotic and educational points of view in the context of students' difficulties and the design of teaching and curricula

Expectations and outcomes of prolonged mechanical ventilation*

Prolonged mechanical ventilation (PMV) provision is increasing markedly despite poor patient outcomes. Misunderstanding prognosis in the PMV decision making process could provide an explanation to this phenomenon. Therefore, we aimed to compare PMV decision makers' expectations for long-term patient outcomes with prospectively observed outcomes

Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs

To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs). Design: Cross-sectional electronic survey. Setting: Email-based Research Electronic Data Capture survey. Patients: Neonates undergoing ECMO for respiratory failure at level IV NICUs. Interventions: A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children\u27s Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals. Measurements and main results: Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16-20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9-10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10-15 (60%), and Fio2 22-30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6-7 (45%), PIP of 21-25 (55%), and tidal volume 5-5.9 mL/kg (50%). Conclusions: The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Shannon Information Theory and Molecular Biology

The role and the contribution of Shannon Information Theory to the development of Molecular Biology has been the object of stimulating debates during the last thirty years. This seems to be connected with some semantic charms associated with the use of the word \u201cinformation\u201d in the biological context. Furthermore information itself, if viewed in a broader perspective, is far from being completely defined in a fashion that overcomes the technical level at which the classical Information Theory has been conceived. This review aims at building on the acknowledged contribution of Shannon Information Theory to Molecular Biology, so as to discover if it is only a technical tool to analyze DNA and proteinic sequences, or if it can rise, at least in perspective, to a higher role that exerts an influence on the construction of a suitable model for handling the genetic information in Molecular Biology