MR-Spektroskopie bei metachromatischer Leukodystrophie

Mittels MR-Spektroskopie konnten in vivo zerebrale Metabolitenkonzentrationsunterschiede zwischen spätinfantilen und juvenilen MLD Patienten sowie Kontrollprobanden gemessen werden. Die MRS Parameter korrelierten dabei mit der motorischen und kognitiven Funktion von MLD Patienten und sind damit nicht nur biologisch, sondern auch klinisch sinnvolle Parameter. Eine höhere Konzentration an Myo-Inositol und Cholin, sowie eine niedrigere Konzentration an Kreatin, Glutamin und NAA gehen mit einer deutlicheren Einschränkung der Patienten einher und lassen Rückschlüsse auf den Fortschritt von Demyelinisierungsprozessen zu. Die schwerer betroffenen spätinfantilen MLD Patienten weisen eine stärkere Abweichung der Metabolitkonzentrationen von den Kontrollprobanden auf als die weniger von der Erkrankung betroffenen juvenilen MLD Patienten. MLD Patienten, die vor allem motorisch eingeschränkt sind, zeigen im Vergleich zu Kontrollprobanden stärkere Metabolitkonzentrationsunterschiede im kortikospinalen Trakt. Kognitiv eingeschränkte MLD Patienten, weisen vor allem Metabolitkonzentrationsunterschiede im frontalen Marklager auf. Generell war bei MLD Patienten die weiße Substanz stärker betroffen als die kaum von gesunden Kontrollprobanden zu unterscheidende graue Substanz, passend zur Pathophysiologie einer primären Leukodystrophie. Die MR-Spektroskopie als Methode erlaubt tieferen Einblick in biochemische Prozesse und kann zu einem tieferen Verständnis der MLD führen. MR-Spektroskopie könnte bei der Therapieplanung helfen, als Surrogatparameter, um Therapieerfolg zu monitoren. Zudem können die MRS-Parameter als sekundärer Endpunkt dienen. Die neue Herangehensweise der Datenauswertung über flexibel auswählbare, intervallorientierte Spektren als Modell-freie Methode, ermöglicht die Quantifizierung von Metaboliten, die von herkömmlichen MR-Spektroskopie Auswertungsprogrammen möglicherweise nicht erkannt werden. Dies ermöglicht die Erforschung von bisher unbeachteten Metabolitkonzentrationsänderungen, die sich auch in Überschneidungsbereichen verschiedener, gewissen Metaboliten zugeordneter Spektren abspielt. Von den für diese Arbeit ausgewerteten 10 Messintervallen scheint der dem Metabolit NAA zugeordnete Bereich am vielversprechendsten als Parameter zur objektivierbaren Einschätzung des MLD Krankheitsprogresses und zur Überwachung des Therapieverlaufs

Future heat extremes and impacts in a convection permitting climate ensemble over Germany

Heat extremes and associated impacts are considered the most pressing issue for German regional governments with respect to climate adaptation. We explore the potential of an unique high-resolution convection permitting (2.8 km), multi-GCM ensemble with COSMO-CLM regional simulations (1971&ndash;2100) over Germany regarding heat extremes and related impacts. We find an improved mean temperature beyond the effect of a better representation of orography on the convection permitting scale, with reduced bias particularly during summer. The projected increase in temperature and its variance favors the development of longer and hotter heat waves, especially in late summer and early autumn. In a 2&deg; (3&deg;) warmer world, a 26 % (100 %) increase in the Heat Wave Magnitude Index is anticipated. Human heat stress (UTCI &gt; 32&deg;C) and local-specific parameters tailored to climate adaptation, revealed a dependency on the major landscapes, resulting in significant higher heat exposure in flat regions as the Rhine Valley, accompanied by the strongest absolute increase. A non-linear, exponential increase is anticipated for parameters characterizing strong heat stress (UTCI &gt; 32&deg;C, tropical nights, very hot days). Providing local-specific and tailored climate information, we demonstrate the potential of convection permitting simulations to facilitate improved impact studies and narrow the gap between climate modelling and stakeholder requirements for climate adaptation.</p

Climate change signals of extreme precipitation return levels for Germany in a transient convection‐permitting simulation ensemble

The increase in extreme precipitation with global warming (GW) and associated uncertainties are major challenges for climate adaptation. To project future extreme precipitation on different time and intensity scales (return periods [RPs] from 1 to 100 a and durations from 1 h to 3 days), we use a novel convection-permitting (CP), multi-global climate model ensemble of COSMO-CLM regional simulations with a transient projection time (1971–2100) over Germany. We find an added value of the CP scale (2.8 km) with respect to the representation of hourly extreme precipitation intensities compared to the coarser scale with parametrized deep convection (7 km). In general, the return levels (RLs) calculated from the CP simulations are in better agreement with those of the conventional observation-based risk products for the region for short event durations than for longer durations, where an overestimation by the simulation-based results was found. A maximum climate change signal of 6–8.5% increase per degree of GW is projected within the CP ensemble, with the largest changes expected for short durations and long RPs. Analysis of the uncertainty in the climate change signal shows a substantial residual standard deviation of a linear approximation, highlighting the need for transient data sets instead of time-slice experiments to increase confidence in the estimates. Furthermore, the ensemble spread is found to be smallest for intensities of short duration, where changes are expected to be based mainly on thermodynamic contributions. The ensemble spread is larger for long, multi-day durations, where a stronger dependence on the dynamical component is ascribed. In addition, an increase in spatial variance of the RLs with GW implies a more variable future climate and points to an increasing importance of accounting for uncertainties

Fungal transformation of selenium and tellurium located in a volcanogenic sulfide deposit

© 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.Peer reviewedPostprin

Identifying seaweed consumption by sheep using isotope analysis of their bones and teeth : Modern reference δ13C and δ15N values and their archaeological implications

This research was funded by the British Natural Environment Research Council (NERC; NER/B/S/2003/00223) and the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme. Stable isotope values in tooth enamel were measured at the SSMIM (Paris, MNHN) with technical support of Joël Ughetto. Modern sheep mandibles and/or information on sheep herding practices on Orkney were kindly provided by Robert Mainland (Rousay), Linda Haganand Una Gordon (Holm of Aikerness), Billy Muir, Dr Kevin Woodbridge and the North Ronaldsay Sheep Court (North Ronaldsay). We would like to thank Anne Brundle, Tankerness House Museum, Orkney (Point of Cott), Dr Colleen Batey, University of Glasgow (Earl’s Bu) and ProfJane Downes and Nick Card, Orkney College, UHI (Mine Howe) for providing access to the archaeological mandibles. The authors would also like to thank Jane Outram and Mandy Jay for assistance in preparation and isotopic measurement of the vegetation samples, which were kindly collected by Robert Craigie, and Karen Chapman for preparing the mandibles. Lastly, the authors are also grateful for the constructive comments of the editors and anonymous reviewers.Peer reviewedPostprin

Fungal formation of selenium and tellurium nanoparticles

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Tracking a Tuberculosis Outbreak Over 21 Years: Strain-Specific Single-Nucleotide Polymorphism Typing Combined With Targeted Whole-Genome Sequencing

Background. Whole-genome sequencing (WGS) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. We combined strain-specific single-nucleotide polymorphism (SNP) typing and targeted WGS to investigate a tuberculosis cluster spanning 21 years in Bern, Switzerland. Methods. On the basis of genome sequences of 3 historical outbreak Mycobacterium tuberculosis isolates, we developed a strain-specific SNP-typing assay to identify further cases. We screened 1642 patient isolates and performed WGS on all identified cluster isolates. We extracted SNPs to construct genomic networks. Clinical and social data were retrospectively collected. Results. We identified 68 patients associated with the outbreak strain. Most received a tuberculosis diagnosis in 1991-1995, but cases were observed until 2011. Two thirds were homeless and/or substance abusers. Targeted WGS revealed 133 variable SNP positions among outbreak isolates. Genomic network analyses suggested a single origin of the outbreak, with subsequent division into 3 subclusters. Isolates from patients with confirmed epidemiological links differed by 0-11 SNPs. Conclusions. Strain-specific SNP genotyping allowed rapid and inexpensive identification of M. tuberculosis outbreak isolates in a population-based strain collection. Subsequent targeted WGS provided detailed insights into transmission dynamics. This combined approach could be applied to track bacterial pathogens in real time and at high resolutio