Über die Wirkung von Mischungen eines antigenhaltigen Plasmas mit einem antikörperhaltigen Serum auf die Entwicklung des Fremdkörpergranuloms

Summary It has been shown that local application of a mixture of precipitating antiserum with homologous plasma or serum promotes markedly the growth of granuloma tissue in the rat.     

Leichtflüchtige Stoffe inAgaricus bisporus

Summary The composition of the volatile fractions (isolated by acidic steam distillation) of the spores, substrate mycelium and fruiting body of the common mushroom is investigated. The physiological and/or biochemical functions of some of the identified substances are discussed.     

Parathymische Lymphknoten der Maus und ihre Reaktion auf Thymektomie

Summary The effect of complete and partial, neonatal thymectomy on parathymic lymphnodes was investigated in NMRI-mice. The results indicate that neonatal extirpation of thymic tissue causes an increase in size and number of parathymic lymphnodes.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.

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Herrn Prof. Dr.O. Westphal zum 60. Geburtstag.     

Hemmung der durch Proteuslipopolysaccharide gesteigerten Leukozytenemigration in vitro durch antiinflammatorische Corticosteroide

Summary The migration of leucocytes from the buffy coat of chicken blood is slightly but irregulatly inhibited by cortison. If migration of leucocytes is increased by proteus lipopolysaccharide, cortison in concentrations of 10^–4–10^–6, and other anti-inflammatory steroids, produce a pronounced and constant inhibition of leucocytic migration.     

S → N acetyl migration in yeast glyceraldehyde-3-phosphate dehydrogenase

Zusammenfassung Nachweis, dass bei der Hefe-GAPD-katalysierten PNPA-Hydrolyse das als Zwischenprodukt gebildete S-Acetyl-Enzym durch eine intramolekulare Wanderung zu einem N-Acetyl-Derivat führen kann. Im Gegensatz zu dem aus Muskel isolierten Enzym findet im Hefe-Enzym eine Acetylwanderung bzw. eine Acetylierung des gegebenen Lysin statt, ohne wesentliche Beeinflussung durch das Coenzym (NAD).     

Histochemische Untersuchungen zur Natur der Cytoplasma-Einschlüsse des Lungentumors der Maus

Résumé Dans une étude histochimique on a montré que les inclusions cytoplasmiques des tumeurs pulmonaires de la souris (Klärner etGieseking) contenaient une polysaccharide neutre jointe à l'acide ribonucléique. Les résultats ont été discutés au sens d'une hypothèse virale.     

Ubiquitin-dependent regulation of COPII coat size and function

Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60-80?nm in diameter, yet some must increase their size to accommodate 300-400?nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive. Here, we identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat formation. CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats. As a result, ubiquitylation by CUL3-KLHL12 is essential for collagen export, yet less important for the transport of small cargo. We conclude that monoubiquitylation controls the size and function of a vesicle coat.     

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.