Untersuchungen über die Bildung der Reblaus-Blattgalle

Résumé La transmission expérimentale de la salive du Phylloxéra peut stimuler les jeunes feuilles de la vigne se trouvant encore dans la phase de végétation à former des galles. A cet égard, l'endopolyploidisation du tissu foliaire qui est exposé à la stimulation de la formation gallicole prouve un événement fondamental de la cécidogenèse.     

Genetische und biochemische Untersuchungen über die Bedeutung der Amino- und Nucleinsäuren im Ursachengefüge von Neoplasmen (Tumoren und Gallen). Ein Dauermodifikationsbzw. Prädeterminationsphänomen

Summary If certain hybrids ofPlatypoecilus maculatus andXiphophorus helleri (viviparous platyfish and swordtails) are cultivated in diluted sea-water (0.25 or 0.5% salt concentration), the amount of free amino acids increases and the growth of macromelanophores, which normally only form certain black spots at the dorsal fin, is accelerated. Therefore melanomas arise. After changing salt water for fresh water, growth of macromelanophores remains accelerated. The same effect is seen in progenies which have been in an oocytic or embryonic state, when their mother was cultivated for some weeks in diluted sea-water (Figures 1 and 2). A similar effect has been observed in plant galls produced byPhylloxera (Viteus vitifolii) in the genusVitis. When the parasite, which injects amino acids into the tissue of the host in order to produce galls, is removed, gall formation goes on slowly for some days. It is shown that a few hours after injection of amino acids—before formation of neoplasms begins—the concentration of ribonucleic acids is increased. RNS-(and therefore protein-)biosynthesis in neoplasms may be dependent on concentration of free amino acids. A simple concept for the formation of neoplasms in hybrids of platyfish and galls ofPhylloxera is discussed.

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Den Herren Prof. Dr.G. de Lattin (Zoologisches Institut der Universität des Saarlandes) und Prof. Dr.B. Husfeld (Forschungsinstitut für Rebenzüchtung Geilweilerhof/Pfalz) sind wir für die Förderung dieser Arbeit zu grösstem Dank verpflichtet. Herrn Prof. Dr.C. Kosswig (Zoologisches Institut der Universität Hamburg) verdanken wir viele Anregungen und die freundliche Überlassung von ingezüchteten Stämmen für unsere Fischkreuzungen. — Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Structure of the cross-beta spine of amyloid-like fibrils

Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast protein Sup35, conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from which we have determined the atomic structure of the cross-beta spine. It is a double beta-sheet, with each sheet formed from parallel segments stacked in register. Side chains protruding from the two sheets form a dry, tightly self-complementing steric zipper, bonding the sheets. Within each sheet, every segment is bound to its two neighbouring segments through stacks of both backbone and side-chain hydrogen bonds. The structure illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.     

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.     

Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy

Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei.