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Spirometry is the most commonly used pulmonary function test. The aim of this comparative study was to evaluate four commercially available spirometers with different measurement principles (turbine-, ultrasound-, differential pressure- and hot-wire anemometer). In particular, the measurement accuracy in breathing manoeuvres with low flow rates was investigated, which is highly relevant for paediatric use. Among the tested devices the hot-wire based spirometer showed the highest measurement accuracy at low flows whilst fully complying with the ATS/ERS standards.

Die absoluten Level von 5-Hydroxymethyl- (hmC) und 5-Methylcytosin (mC) in humanen Hirngeweben wurden in Abhangigkeit vom Lebensalter bestimmt. Zusatzlich wurden die absoluten 5-Formylcytosin-Level (fC) in adulten Individuen und die Level dieser modifizierten Cytosinbasen in menschlichen Neuronen quantifiziert. Wir vergleichen diese Daten mit den altersabhangigen Mengen von fC, hmC und mC in Hirngeweben der Maus. Bei hmC wird mit zunehmendem Alter zunachst ein Anstieg der Modifikationsdichte beobachtet. Im voll entwickelten Gehirn steigt das hmC-Level nicht weiter an, sondern bleibt auf einem konstant hohen Niveau von ca. 1.2 % beim Menschen. Dieser Wert ist etwa doppelt so hoch wie das hmC-Level im zerebralen Cortex der adulten Maus. Im Unterschied dazu sinkt das fC-Level in den fruhen Entwicklungsstadien mit zunehmendem Alter stark ab. Bei hmC konnte es sich dementsprechend um eine stabile epigenetische Modifikation handeln, wahrend fC in den fruhen Gehirnentwicklungsphasen vermutlich eher als Intermediat der aktiven DNA-Demethylierung auftritt.

The absolute levels of 5-hydroxymethylcytosine (hmC) and 5-methylcytosine (mC) in human brain tissues at various ages were determined. Additionally, absolute levels of 5-formylcytosine (fC) in adult individuals and cytosine modification levels in sorted neurons were quantified. These data were compared with age-related fC, hmC, and mC levels in mouse brain samples. For hmC, an initial steady increase is observed, which levels off with age to a final steady-state value of 1.2 % in human brain tissue. This level is nearly twice as high as in mouse cerebral cortex. In contrast, fC declines rapidly with age during early developmental stages, thus suggesting that while hmC is a stable epigenetic mark, fC is more likely an intermediate of active DNA demethylation during early brain development. The trends in global cytosine modification dynamics during the lifespan of an organism are conserved between humans and mice and show similar patterns in different organs.

SummaryTen-eleven translocation hydroxylases (TET1-3) oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). In neurons, increased 5hmC levels within gene bodies correlate positively with gene expression. The mechanisms controlling TET activity and 5hmC levels are poorly understood. In particular, it is not known how the neuronal TET3 isoform lacking a DNA-binding domain is targeted to the DNA. To identify factors binding to TET3, we screened for proteins that co-precipitate with TET3 from mouse retina and identified the transcriptional repressor REST as a highly enriched TET3-specific interactor. REST was able to enhance TET3 hydroxylase activity after co-expression and overexpression of TET3-activated transcription of REST target genes. Moreover, we found that TET3 also interacts with NSD3 and two other H3K36 methyltransferases and is able to induce H3K36 trimethylation. We propose a mechanism for transcriptional activation in neurons that involves REST-guided targeting of TET3 to the DNA for directed 5hmC generation and NSD3-mediated H3K36 trimethylation.