Analysis of the coding genome of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular pathways, remains unknown. By combining next-generation sequencing and copy number analysis, we show that the DLBCL coding genome contains, on average, more than 30 clonally represented gene alterations per case. This analysis also revealed mutations in genes not previously implicated in DLBCL pathogenesis, including those regulating chromatin methylation (MLL2; 24% of samples) and immune recognition by T cells. These results provide initial data on the complexity of the DLBCL coding genome and identify novel dysregulated pathways underlying its pathogenesis.     

Comparative myogenesis in teleosts and mammals

Skeletal myogenesis has been and is currently under extensive study in both mammals and teleosts, with the latter providing a good model for skeletal myogenesis because of their flexible and conserved genome. Parallel investigations of muscle studies using both these models have strongly accelerated the advances in the field. However, when transferring the knowledge from one model to the other, it is important to take into account both their similarities and differences. The main difficulties in comparing mammals and teleosts arise from their different temporal development. Conserved aspects can be seen for muscle developmental origin and segmentation, and for the presence of multiple myogenic waves. Among the divergences, many fish have an indeterminate growth capacity throughout their entire life span, which is absent in mammals, thus implying different post-natal growth mechanisms. This review covers the current state of the art on myogenesis, with a focus on the most conserved and divergent aspects between mammals and teleosts.     

The positional identity of mouse ES cell-generated neurons is affected by BMP signaling

We investigated the effects of bone morphogenetic proteins (BMPs) in determining the positional identity of neurons generated in vitro from mouse embryonic stem cells (ESCs), an aspect that has been neglected thus far. Classical embryological studies in lower vertebrates indicate that BMPs inhibit the default fate of pluripotent embryonic cells, which is both neural and anterior. Moreover, mammalian ESCs generate neurons more efficiently when cultured in a minimal medium containing BMP inhibitors. In this paper, we show that mouse ESCs produce, secrete, and respond to BMPs during in vitro neural differentiation. After neuralization in a minimal medium, differentiated ESCs show a gene expression profile consistent with a midbrain identity, as evaluated by the analysis of a number of markers of anterior–posterior and dorsoventral identity. We found that BMPs endogenously produced during neural differentiation mainly act by inhibiting the expression of a telencephalic gene profile, which was revealed by the treatment with Noggin or with other BMP inhibitors. To better characterize the effect of BMPs on positional fate, we compared the global gene expression profiles of differentiated ESCs with those of embryonic forebrain, midbrain, and hindbrain. Both Noggin and retinoic acid (RA) support neuronal differentiation of ESCs, but they show different effects on their positional identity: whereas RA supports the typical gene expression profile of hindbrain neurons, Noggin induces a profile characteristic of dorsal telencephalic neurons. Our findings show that endogenously produced BMPs affect the positional identity of the neurons that ESCs spontaneously generate when differentiating in vitro in a minimal medium. The data also support the existence of an intrinsic program of neuronal differentiation with dorsal telencephalic identity. Our method of ESC neuralization allows for fast differentiation of neural cells via the same signals found during in vivo embryonic development and for the acquisition of cortical identity by the inhibition of BMP alone.     

Dependence of Ypt1 and Sec4 membrane attachment on Bet2

Many small GTP-binding proteins are synthesized as soluble proteins that are post-translationally modified as a prerequisite for membrane attachment. Ypt1 and Sec4 are homologous Raslike GTP-binding proteins that have been proposed to regulate the specificity of vesicular traffic at different stages of the secretory pathway by cycling on and off membranes. Here we show that BET2, initially identified as a gene required for transport from endoplasmic reticulum to Golgi apparatus in yeast, encodes a factor that is needed for the membrane attachment of Ypt1 and Sec4. DNA sequence analysis has revealed that Bet2 is homologous to Dpr1 (Ram1), an essential component of a protein prenyltransferase that modifies Ras, enabling it to attach to membranes. We propose that Bet2 modifies Ypt1 and Sec4 in an analogous manner.     

Immunoglobulins in human fetal sera at different stages of gestation

Zusammenfassung Durch quantitative Immunodiffusion wurde der Gehalt an IgM, IgA und IgG in menschlichen Fötalseren untersucht. Der früheste Zeitpunkt, wo IgA entdeckt wurde, war bei einem prämaturen Embryo, der 41 cm lang war und 1680 g wog. In den Seren von am Termin geborenen Kindern konnte IgA in 37% nachgewiesen werden. IgG wurde in allen untersuchten Seren gefunden.

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Supported by a grant from the Sigrid Jusélius Foundation.     

Elektronenoptische Beobachtungen bei Speicherkrankheiten

Summary Ultrastructural changes in spleen and liver in a case ofMorbus Gaucher andNiemann-Pick are discussed.The results are: (1) The Ultrastructure shows a distinct differentiation between the two diseases. (2) It seems that storage begins in mitochondria. (3) In the case ofMorbus Niemann-Pick, all Mitochondria of storage cells show an abnormal ultrastructure (diminuation in size, increased osmiophilia, disorder in the arrangement of cristae and membranes).

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Die Arbeit erscheint ausführlich an anderer Stelle.     

The use of benzylpenicillinacylase fromEscherichia coli in the resolution of some racemicβ-,γ-,δ- andɛ-amino-acids

Summary The enzymatic hydrolysis of N-phenylacetyl derivatives of racemic amino-acids having the chiral centre removed from the usual -position is examined. The reaction is found to have different degrees of stereoselectivity. In the case of -amino-acids and of -aminovaleric acid, both enantiomers can be obtained in good yields and high optical purity. S-directed stereochemical preference was found for all the substrates examined.